BROEGELMANN RESEARCH LABORATORY Department of Microbiology and Immunology The Gade Institute

Haukeland University Hospital - Faculty of Medicine University of Bergen

ANNUAL REPORT 1998

Postal address: Broegelmann Research Laboratory Armauer Hansen Bldg N-5021 Bergen, Norway Tel: +47-55974648 or 55974649 Fax: +47-55975817 E-mail: [email protected] or [email protected] http://www.uib.no/Broegelmann

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Administration - personnel - scientists Administration Technical and administrative personnel Postdoctoral positions Visiting scientists Trainees

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Teaching Postgraduate teaching Guestlectures

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Scientific activity Completed thesis work Aims of research Collaborating institutions Major projects Collaborating projects Projects supported by the EU-Biomed 2 Publications Abstracts

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External activity

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1.

Administration - personnel - scientists

The Broegelmann Research Laboratory (BRL) is an immunology research unit at the University of Bergen and Haukeland University Hospital. The Laboratory is co-localized/affiliated with and has a scientific and technical collaboration with the Department of Microbiology and Immunology, the Gade Institute. The core financial support comes from the Broegelmann Foundation.

RESEARCH AREAS:

Autoimmunity/chronic inflammation/host response; molecular medicine; mucosal immunity; immunopathology; vaccine development; tumour immunology; nutrition and immunology.

HEAD OF LABORATORY (from 1991): Roland Jonsson DMD, PhD, professor of medicine (immunology)

TECHNICAL/ADMINISTRATIVE PERSONNEL: Kate Frøland (100% adm [30% BFL, 50% EU, 20% NFR]) Turid Tynning (50% BFL+ 50% ENT) Marianne Eidsheim (100% BFL)(maternal leave until 10/98) Katarina Omholt (100% BFL) Merethe Karlsen (50% BFL) 08/98 – 12/98

POSTDOCTORAL POSITIONS: Audun H. Nerland PhD

(molecular biology) (100% 01/98-04/98, 20% 05/98 – 12/98) Anne Isine Bolstad DMD, PhD (molecular immunology/genetics) Kathrine Skarstein DMD, PhD (cellular immunology) (maternal leave 09/98-12/98) Karl A. Brokstad PhD (molecular immunology/biology) (from 11/98)

VISITING SCIENTISTS: Martin Sundler, Lund, Sweden Konstantin Iakimtchouk, Moscow, Russia Michael Humphreys-Beher PhD, Univ of Florida, USA (visiting professor)

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TRAINEES: Rheumatological immunology (Jonsson) Principal supervisor(s) Anne-Kristine Halse MD, doctoral degree student Jonsson Maria Ohlsson Msc, doctoral degr student (fr 09/98) Brokstad/Jonsson Konstantin Iakimtchouk MD, master degr stud (fr 09/98) Brokstad/Jonsson Genetics in chronic inflammatory disease (Bolstad) Britt Nakken, cand mag, doctoral degree student

Bolstad/Jonsson

Mucosal immunobiology (Jonsson) Knut Hordnes MD, doctoral degree student (until 02/98) Ivana Pereira Nunes DMD, doctoral degree student Seth Adu-Afarwuah Georg Tuwor

Jonsson/Haneberg Jensen/Bakken/Jonsson Lied/Jonsson Lied

Mycobacterial immunity/vaccine development (Nerland) Feseha Abebe MSc, doctoral degree student Lise Schaug-Pettersen, cand scient/”hovedfag” student Azeb Tadesse MD, doctoral degree student Ingunn Sommerset, cand scient/”hovedfag” student Yoseph Haile Msc, doctoral degree student

Nerland/Bjune Nerland Nerland/Bjune Nerland/Bakken Nerland/Bjune/Wiker

Affiliated with Broegelmann Research Laboratory (doctoral/master degree studies): Vaska Vandevska DMD, Dept of Anat, UoB Kvinnsland/Jonsson Ånen Aarli MD, Dept of Pediatrics, UoB Matre Tone Skeie Jensen MD, Dept of Gynecology, UoB Matre Tehmina Mustafa MD, Center for Int Health, UoB Bjune/Nilsen Sabay Phyu MD, Center for Int Health, UoB Bjune Pia Tengnér MD, Karolinska Inst, Sweden Wahren-Herlenius/Jonsson Jon-Helge Heimdal MD, Dept of ENT, UoB Aarstad/Olofsson Carla Olsnes, Dept of ENT, UoB Aarstad James Lado Loro DMD, Dept of Oral Pathol, UoB Johannessen/Vintermyr/Jonsson Evelyn Neppelberg DMD, Dept of Oral Surgery, UoB Johannessen/Jonsson Torbjørn Breivik DMD, Dept of Periodontol, UoO Gjermo/Jonsson Selemawit Tadezze, Center for Int Health, UoB Bjune Tzige Weine Tesema MD, Center for Int Health, UoB Bjorvatn Affiliated with the laboratory (without current/immidiate degree studies): Roland Jureen MD, Dept of Microbiol/Immunol, UoB Nerland Pål Voltersvik MD, Dept of Medicine, UoB Åsjö Medical students (e.g. special reports): Bjørn Magne Jåtun Paal Methlie Hansen Lisbeth Homlong

Nerland Nerland Bolstad

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ADDITIONAL SCIENTISTS/KEY-COLLABORATORS AFFILIATED WITH THE LABORATORY AND WITH E.G. SUPERVISION FUNCTIONS PLUS JOINT PUBLICATIONS: assoc prof Vidar Bakken, Laboratory for Oral Microbiology professor Gunnar Bjune, Centre for Int Health, Univ of Bergen and Oslo dr med Johan G. Brun, Div of Rheumatology, Med Dept B, Haukel Univ Hospital professor Nils-Erik Gilhus, Dept of Neurology, Haukeland Univ Hospital professor Hans-Jacob Haga, Div of Rheumatology, Med Dept B, Haukel Univ Hospital professor Lars R. Haaheim, Inst of Molecular Biology professor Bjørn Haneberg, National Inst of Publ Health professor Henrik Hellquist, Dept of Pathology, The Gade Inst assoc professor Eystein Husebye, Medical Dept B, Haukeland Univ Hospital dr scient Beate Klementsen, Dept of Otolaryngol/Head & Neck Surgery professor Inger Kvinnsland, Inst of Anatomy professor Einar Lied, Directorate of Fisheries professor Harald Jensen, Inst of Molecular Biology professor Anne C. Johannessen, Dept of Oral Pathology, The Gade Institute professor Rune Nilsen, Centre for International Health professor Jan Olofsson, Department of Otolaryngology/Head & Neck Surgery, Haukeland Univ Hospital assoc professor Hans-Jørgen Aarstad, Department of Otolaryngology/Head & Neck Surgery, Haukeland Univ Hospital professor Birgitta Åsjö, Center for Virology

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Teaching

POSTGRADUATE TEACHING: Continuesly during the spring and fall semesters a seminar series was conducted every week with presentations from invited speakers. On a weekly basis seminars were given related to research areas of the students/trainees. Guest lectures are an important part of intellectual stimulation. The scientists were teaching immunological techniques, autoimmunity, mucosal immunity and oral medicine in postgraduate courses and at other invited situations both at national and international gatherings. COURSES PROVIDED:

Immunological techniques, March 24-26

EXCURSIONS AND EXTERNAL SEMINARS: 11-13/09

Seminar at Drægo, Dyrdal “Current research activity at BRL incl. strategic discussions”

GUESTLECTURES AND VISITORS AT BRL: 19/02

Prof. Catharina Svanborg, Lund University, Sweden “Microbial induction of mucosal inflammation”

27/02

Prof. Ole Petter Rekvig, University of Tromsø, Norway “Studies of cellular and molecular mechanisms for production of antiDNA antibodies”

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03/04

Prof. Morten Harboe, University of Oslo, Norway “Secreted protein antigens of mycobacteria – demonstration and significance”

15/05

Prof. William J. Koopman, The University of Alabama at Birmingham, USA “New therapeutic directions in the treatment of rheumatic disease” ( The 1998 Broegelmann Lecture )

05/06

Prof. Michael Humphreys-Beher, The University of Florida, USA “Is the immune system the enemy in autoimmunity? Lessons from the NOD mouse model for Sjögren´s syndrome”

19/06

Dr. Ulf Dahlgren, University of Göteborg, Sweden “Oral tolerance to food proteins and bacteria”

19/10

Dr. Richard F. Konz, CompuCyte Corporation, USA “Laser Scanning Cytometry”

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Scientific activity

COMPLETED THESIS WORKS IN 1998 WITH CONTRIBUTIONS FROM BRL: Hordnes K: Mucosal immunity to group B streptococci in the female genital tract - prospects for development of a mucosal vaccine; dr med, thesis defence 20/2 1998. Principal Institute: Broegelmann Research Laboratory, UoB. Tadesse A: Organ specific in vivo and in vitro cytokine production in chronic murine tuberculosis; master phil (immunology), thesis defence 23/6 1998. Principal Institute: Centre for International Health, and Broegelmann Research Laboratory, UoB. Vandevska-Radunovic V: Neural modulation of inflammatory reactions in rat dental tissues incident to orthodontic tooth movement; dr odont, thesis defence 6/10, 1998. Principal Institute: Department of Anatomy and Cell Biology, UoB. Adu-Afarwuah Seth: Effects of fish-protein supplementation on some aspects of humoral immunity: a study with Ghanaian children; master phil health sci (nutrition), thesis defence 25/8, 1998. Principal Institute: Directorate of Fisheries, UoB. Aarli Å: Annexin II - an IgG-binding protein with immunosuppressive properties; dr med, thesis defence 23/10 1998. Principal Institute: Department of Microbiology and Immunology, and Broegelmann Research Laboratory, UoB.

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SPECIFIC AIMS OF THE RESEARCH AT BRL: The laboratory targets its efforts within the fields of autoimmunity, mucosal immunity, immunopathology and tumour immunology. The work is directed towards basic immunological questions incl. genetics in rheumatological and mucosal immunity as well as clinical immunological topics. Furthermore, experimental autoimmune/rheumatological research is conducted in murine systems. The laboratory work is performed with immunomorphological and functional immunological techniques at both cellular and molecular levels in human and murine tissues, sera, and secretions as well as in tissue- and cell-cultures. Specific areas of interest are summarized below:

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AUTOIMMUNITY

Autoimmune reactions are of central importance in the etiology of many somatic diseases. Different tissues can be affected in different ways but a common denominator is a chronic inflammation which can result in tissue damage and accompaning loss of function. Our aim is to study disease mechanisms in connective tissue diseases (Sjögren's syndrome and rheumatoid arthritis) with special reference to exocrine gland and joint tissue. For this purpose we combine studies in both human and murine systems, which hopefully will help us in elucidating pathogenic mechanisms and more recently the genetic background as a basis for better diagnosis and therapy. The immunological aspect is concerned with cellular and molecular characterization of lesions, quantitation of humoral and cellular immune responses against endogenous and exogenous antigens, as well as attempts at immunomodulation. Special attention is given to programmed cell death (apoptosis) in relation to chronic inflammatory disorders (Sjögren's syndrome, rheumatoid arthritis, adult periodontitis).

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MUCOSAL IMMUNITY

Mucous membranes constitute important defence mechanisms for the body and contain important humoral effector functions via the humoral immune system. A change in the regulation of immunity can however give rise to undesirable side effects which may result in tissue lesions in mucous membranes of the oral cavity, the gastro-intestine, the vagina, the lungs, the exocrine glands etc. Furthermore, the body is normally confronted with the first antigen contact/stimulation through the mucous membranes. Our aim is to study antigen presentation in mucous membranes and to characterize defence mechanisms and pathological immunological situations. Knowledge obtained within this field is of particular importance for better diagnostic and preventive/ treatment measures e.g. vaccines.

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MYCOBACTERIAL IMMUNITY

Tuberculosis is today the most important infectious disease world-wide. The currently used BCG vaccine has variable effect on primary tuberculosis, but little or no effect on reactivated tuberculosis. The aim of the project is to use molecular biology to characterize the individual antigens of M. tuberculosis and characterize the immune response at mucosal surfaces and in lymphoid organs in order to find suitable antigens for a future recombinant vaccine.

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TUMOUR IMMUNOLOGY

The immune system obviously has an important role in the development of malignant tumours. Our interests within this are: role of T-cells, macrophages, cytokines and apoptosis incl. regulating molecules in tumour development.

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The scientific activity at BRL is concentrated much on an international profile with a vast network. Internationally BRL has kept and established contact with more than 10 foreign research institutions, mainly in Sweden, other European countries and USA. The work is characterized by "crossing" scientific fields aiming both towards clinical and basic research.

COLLABORATION IS ESTABLISHED WITH THE FOLLOWING LOCAL RESEARCH INSTITUTIONS: A. B. C. D. E. F. G. H.

Department of Microbiology and Immunology, Sections for immunology, bacteriology and virology, The Gade Institute Division of Rheumatology, Medical Department B Department of Otolaryngology/Head & Neck Surgery Clinical Molecular Medicine/Dept of Medical Genetics Centre for International Health Department of Pathology and Oral Pathology, The Gade Institute Laboratory for Oral Microbiology Department of Obstetrics and Gynecology

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In addition, collaboration (joint grants/publications and/or sharing of reagents/materials) is established with the following laboratories/institutions:

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Experimental rheumatic disease in murine models (R. Holmdahl, Dept of Medical Inflammation Research, Lund Univ, Sweden) Apoptosis and Fas antigen (J. Mountz, Division of Clinical Immunology and Rheumatology, Univ of Alabama at Birmingham, AL, USA) Immunology of rheumatic disease (H. Carlsten & A. Tarkowski, Dept of Clinical Immunology, Univ of Göteborg, Sweden) Potential viral etiology of autoantibody (Ro) production (J. Harley, Arthritis and Immunology Program, Oklahoma Medical Research Foundation, OK, USA) Anti-Ro and anti-La antibody studies (M. Wahren, Dept of Medical Cell Genetics, Medical Nobel Institute, Karolinska Institute, Stockholm, Sverige) Murine Ro and La antigens (T. Gordon, Tissue Typing and Immunogenetics, Australian Red Cross Blood Transfusion Service, Adelaide, Australia) Calprotectin and its biology (M. Fagerhol, Ullevål Hospital, Oslo) Experimental models of Sjögren's syndrome (Michael Humphreys-Beher, Univ of Florida, Gainesville, FL, USA) Vaccine development and mucosal immunity (B. Haneberg, National Institute of Public Health, Oslo, Norway)

2. 3. 4. 5. 6. 7. 8. 9.

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Project supported by the European Union (EU) - Biomed II: «Sjögren´s syndrome - A strategy for clarifying the disease process that underlies a chronic disorder of the mucous membranes» Contract Nr.: BMH4-CT96-0595 Basic Research Project EU Contribution: 410,000 ECU Starting date: spring/96 Duration: 46 months

Coordinator Prof Roland Jonsson Tel: +47-55 97 46 48 Fax: +47-55 97 58 17

EC Scientific Officer: Mr. Heikki Kallasvaara Fax: +32-2-295 5365 Prof Josef S. Smolen Prof Joachim R. Kalden Prof Haralampos M. Moutsopoulos Prof Claudio Vitali Prof Jacob B. Natvig Dr Marie Wahren Prof Rikard Holmdahl Dr Rolf Manthorpe Prof David Isenberg

Partners

Vienna, Austria Erlangen, Germany Athens, Greece Pisa, Italy Oslo, Norway Stockholm, Sweden Lund, Sweden Malmö, Sweden London, United Kingdom

Project supported by the European Union (EU) - Biomed II: «The genetics of systemic lupus erythematosus and Sjögren´s syndrome» Contract Nr.: BMH4-CT98-3489 Basic Research Project EU Contribution: 1.200 Mill ECU Starting date: Duration:

Coordinator Prof. Ulf Gyllensten Dr Marta Alarcon-Riquelme Tel: +46-18-513784 Fax: +46-18-526849

spring/98 36 months

EC Scientific Officer: Mr. Heikki Kallasvaara Fax: +32-2-295 5365 Prof. Lars Klareskog Dr. Gunnar Sturfelt Prof. Paul A. Bacon Dr. Kristján Steinsson Dr. José Ma. Alvaro Gracia Prof. Roland Jonsson Prof Joachim R. Kalden Daniel Commenges VP Mats Sundvall

Partners

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Stockholm, Sweden Lund, Sweden Birmingham, Great Britain Reykjavik, Iceland Madrid, Spain Bergen, Norway Erlangen, Germany Bordeaux, France Uppsala, Sweden

MAJOR SPECIFIC PROJECTS incl. progress report •

Etiopathogenesis of autoimmunity with special reference to Sjögren's syndrome (part of this is PhD thesis work for Halse, Tengnér, Ohlssson and Iakimtchouk) (supported by EU/Biomed II and Research Council of Norway) In the proposed studies we will investigate etiologic and pathogenic mechanisms in Sjögren’s syndrome (SS), by focusing on a potential viral etiology of this autoimmune disease in exocrine glands. The project includes the following specific and long-term objectives: I . Characterization by immunological and molecular biological techniques the tissue distribution of viruses and/or their products at the site of tissue lesion, I I . Investigation of the local and peripheral humoral response (antibody titers and quantitative evaluation of spontaneous immunoglobulin secretion at the single cell level) against endogenous antigens and viruses, I I I . Analysing the fine specificity of antibodies produced by using ‘epitope scanning’ and available databases, IV . Analysing antigen recognition by T-lymphocytes in salivary glands and peripheral blood using synthetic peptides of endogenous antigens and viral sequences, V. Performing polymerase chain reaction analyses on DNA and mRNA from human tissues and generated T-cell lines with the purpose of identifying any dormant versus active genomic viral sequences. It is anticipated that the proposed characterization and elucidation of potential viral etiology and related pathogenic mechanisms in this chronic inflammatory disease will yield direct important clinical insight into these disease processes. This may form a basis for therapeutic measures as well as contribute to our understanding of normal immune reactions in salivary glands.

Progress 1998: Two separate studies have been finished and three papers are published or in press showing local production of anti-Ro/SSA and anti-La/SSB producing cells in salivary glands with in situ detection and ELISPOT techniques, respectively. Another study of the frequency of cytokine production in peripheral blood of SS patients has been finalized and is in press. Genomic HLA-typing of class II alleles of Norwegian anti-Ro/SS-A and anti-La/SS-B positive SS patients have been conducted and will be analyzed in relation to autoantibody phenotype.

• Apoptosis and its role in chronic inflammatory disease (part of this is PhD thesis work for Ohlssson) (supported by EU/Biomed II and Research Council of Norway) The proposed study will focus on the possible role of Fas apoptosis antigen in the etiology and/or development of chronic inflammatory disease (CID) with special emphasis on Sjögren's syndrome. We will test the hypothesis that the abnormal expression of the Fas apoptosis antigen contributes to pathogenesis and development of autoimmune diseases, particularly of those characterized as lymphoproliferative disorders with a production of autoantibodies. To accomplish this goal, the proposal is to pursue four specific aims: I. characterize the constitutive and induced expression of Fas antigen in normal and inflammatory human tissue; I I . determine the correlation of the secreted form of Fas antigen in pathogenesis and/or development of CID; I I I . determine if the abnormal proliferation of lymphocytes is due to defective Fas-mediated apoptosis; IV. identification of associations between Sjögren's syndrome and immune response genes. The significance of the proposed research is underlined by the high prevalence of CID in some of the more common autoimmune diseases. The results of the proposed

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research should let us understand the role of the secreted form of Fas antigen in Fas-Fas ligand mediated apoptosis. The method developed for detection of the secreted Fas antigen is important since the latter may have potential value as an additional marker for clinical diagnosis of CID patients. The conclusion of this research will shed light onto the development of therapies directed toward increasing apoptosis and elimination of these abnormal cells which are present in the CID patients. Progress 1998: One review article has been published and another paper regarding Fas/FasL expression and in situ apoptosis in SS is in preparation. Screening for mutations in the Fas and FasL genes has been performed and data are being summarized for presentation.

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Autoimmunity and pathogenesis of murine sialadenitis (supported by EU/Biomed II and Research Council of Norway) Studies proposed will investigate the immunopathogenesis of sialadenitis in spontaneous and congenic murine models of Sjögren's syndrome. Local responses to potentially immunogenic and endogenous constituents in salivary glands will be investigated. An enzymatic dissociation method evaluated/assessed at this laboratory will permit detailed cellular and molecular analysis of resident and infiltrating lymphoid cell populations present in involved tissue. This project includes the following specific and long-term objectives: I . Characterization, by immunomorphological techniques, of the architecture of immunocompetent cells in salivary glands, I I . Investigation of the characteristics of antigen presentation in murine sialadenitis; in particular, the capacity of salivary glands to generate an immune response after systemic or intraglandular immunization, I I I . Evaluation of infiltrating T cells during the evolution of sialadenitis for patterns of expression of T cell markers and T cell receptors incl. TCR α/β and TCR γ/δ gene expression and production of various lymphokines, IV. Analysis of autoreactivity/pathogenicity among infiltrating mononuclear cells by cell transfer and antigen specific T cell proliferation, V. Carrying out immunomodulation in order to prevent sialadenitis. The availability of autoimmune murine strains, the MRL/Mp-lpr/lpr and the NOD mouse, with spontaneous infiltration of mononuclear cells in salivary glands makes these models uniquely suited for the study of the pathogenesis of sialadenitis. The proposed studies should yield important insights concerning the pathogenesis of Sjögren's syndrome in humans as well as contribute to our understanding of normal immune responses in salivary glands.

Progress 1998: Phenotypic work incl. apoptosis studies are under way in different MHC congenic NOD strains.

• Shared gene analysis and autoimmunity (part of this is PhD thesis work for Nakken) (supported by EU/Biomed II and Research Council of Norway) The longterm goal of the current murine studies is to obtain information about the influence of different genes in the development of sialadenitis as compared to arthritis, encephalomyelitis and diabetes. This is part of a wider approach also involving human genetic studies (candidate genes and whole genome scanning). The current aim is feasible due to already performed backcrossing and breeding of the NOD strain at the University of Lund, Sweden. More specifically the working plan is as follows: 1/ Different NOD congenic strains will be tested for susceptibility to diabetes, sialadenitis, arthritis and encephalomyelitis in order to initially determine the role of MHC/H-2 for the sensitivity of these diseases. 2/ Secondly,

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there will be done F1 hybrids between the strains in order to determine whether MHC plays a disease down-regulatory role. 3/ From these data another strain will be selected to analyse non-MHC genes. The goal is finally to determine the genes controlling susceptibility to autoimmune sialadenitis which might help in identifying the genetic background for human Sjögren's syndrome. Progress 1998: Full genome scanning has been conducted and results are currently being anlayzed as a basis for phenotypic/genotypic correlates.

• The genetics of Sjögren's syndrome; Identification of susceptibility genes (part of this is PhD thesis work for Nakken) (supported by EU/Biomed II and Research Council of Norway) Sjögren's syndrome (SS) is an autoimmune disease of unknown etiology and uncertain pathogenesis affecting predominantly women. Regardless of the actual mechanistic aspects of autoimmunity, population, family and twin studies have clearly shown that genetic factors exert the most significant influence on autoimmune disease predisposition. Current understanding of the genetic factors that contribute to autoimmune disease predisposition indicate that multiple genes contribute to induction of pathogenic autoimmunity, and that no single genetic abnormality is sufficient in itself to induce disease. The ultimate objective of this project is to identify genes involved in the susceptibility for SS. To accomplish this goal, the proposal is to pursue four specific aims: I. clinical and immunological assessment of family material; I I . identification of the chromosomal regions involved in the susceptibility to SS; I I I . identification of the genes involved in the susceptibility of SS and their genetic interactions; IV. development of diagnostic risk and risk assessment markers for clinical use. The experimental approach will include immunological assessment of family material and study of candidate genes parallel with genome scanning approaches, such as development of dense chromosomal maps based on polymorphic microsatellite DNA. Computer analysis will be performed for statistical and linkage analysis. The proposed project will yield important information concerning pathogenesis in SS and shed light on the genetics behind the disease. Progress 1998: Polymorphisms/mutations have been detected in the Fas and FasL gene of primary SS patients. Studies on the Ro 52 and La genes is ongoing and will soon be summarized. A large sample of primary SS patients are currently being analyzed in Germany for HLA-alleles, being part of a more than 300 patients and European study. A Norwegian family material of Sjögren´s syndrome and systemic lupus erythematosus has been collected (incl. clinical data, DNA and serum) and is now ready for gene scanning.

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Induction of cervico-vaginal mucosal immunity against group B streptococci (PhD thesis work for Hordnes) Group B streptococci (GBS) often colonize the birth channel of pregnant women leading to infection of the new-born. This type of infection represents a substantial health problem in many countries world wide. In preliminary experiments of mice we have found that rectal vaccination can produce antibodies in serum and production of specific antibodies against GBS in local secretions. The purpose of this project is to characterize the systemic and local immune response, and map the region of the bacterium which acts as a stimulus to immunity i.e. antigenic determinants. With this as a background the aim is to construct a vaccine to be tested in mice by analysing the obtained protection against infection of GBS in

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cervix/vagina after delivery of the vaccine per anally. In parallel with the murine experiments the immune response in humans will be monitored. If the analysis provide evidence for protection and safety it might be feasible to start phase-I vaccine studies in non-pregnant volunteers. If this proposed immunization will be effective it suggests that infection of new-borns can be prevented. Progress 1998: A thesis has been defended for the dr med degree. Work is currently ongoing for prepartion of a phase I vaccine trial using intra-nasal route of immunization.

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Molecular biology related to mycobacteria (part of this is thesis work for Abebe, Jureen, SchaugPettersen, Sommerset, Tadesse). Tuberculosis is one of the major global health problems today with more than 8 million registered new cases and around 3 million registered deaths yearly (1992). To combat this disease there is a need for 1) faster and more sensitive diagnostic methods, 2) new antibiotics and 3) more efficient vaccines. The aim of the project is development of improved vaccines and sensitive diagnostic methods that can discriminate between different mycobacterial infections. The strategy is cloning of genes encoding relevant antigens of M.tuberculosis into vectors for expression in E.coli, followed by testing out the recombinant antigens for immune stimulation (lymphocyte stimulation test/skin test) and protection in an animal model (mice). In addition, the same DNA sequences will be cloned into suitable vectors and tested out as «DNA vaccines».

Progress 1998: The gene encoding mpt64, an antigen present in M.tuberculosis but not in the M.bovis BCG strain, has been cloned into an E.coli expression vector. This antigen may be suitable to differentiate between vaccinated persons and persons infected with tuberculosis. The gene has also been cloned into an eukaryotic vector, and we are presently testing it for expression in eukaryotic cells (COS-cells) in vitro.

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Immune responses to Fusobacterium nucleatum (PhD thesis work for Nunes) Fusobacterium nucleatum is an anaerobic bacterium commonly isolated from sites of periodontal disease. The cell wall of this bacterium has been extensively studied and purified preparations of the outer membrane are available. The purpose is to compare different antigen preparations for their capacity to elicit a systemic immune response in mice. The second goal is to quantitate at the single cell level the local and peripheral immune response against F. nucleatum in adult periodontitis. Furthermore, the aim is to characterize stimulatory properties of this bacterium and/or derived proteins on T cells. The characterization of the immune response against F. nucleatum will help to elucidate its role in the microbial etiology of adult periodontitis.

Progress 1998: The work has been continued and a human study has been planned.

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OTHER COLLABORATIVE PROJECTS: • Emotional stress effects on immunity, periodontitis and gingivitis (Breivik) Progress 1998: Research are currently being summarized in one paper concerning phenotyping of rat periodontal tissues. The cytokine profile work is being started up.

• Humoral immunity and protein-deficiency

(Lied)

Progress 1998: A «master» thesis has been finalized and defended. Additional analysis is in progress.

• Effects of orthodontic forces on immune cells in the periodontal ligament (Vandevska) Progress 1998: One paper has been accepted concerning immune-phenotyping in orthodontically manipulated periodontal tissues of the rat. A PhD thesis has been defended.

• Clinical evaluation and symptoms of the upper respiratory tract in patients with Sjögren's syndrome (Hultén) Progress 1998: One study related to reliability and sensitivity of diagnostic tests is in press. Further collection of clinical and laboratory data is ongoing.

• Relations between immune functions/cytokines, psychological status and cancer development (Heimdal/Aarstad) Progress 1998: The work is focused at leukocyte studies from peripheral blood of cancer patients. Work on biology of metastases is being initiated; interactions between monocytes and spheroids. Three papers have been published and one is in press.

• Apoptosis in oral cancer

(Lado Loro)

Progress 1998: One study has been finalized and one paper is in press. Another study has been finalized and a paper submitted.

• Effect of phenytoin on immunoglobulin secretion

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(Gilhus)

• B-cell activity (anti-p24 and anti-gp120) in tonsils and peripheral blood from humans with HIV infection (Voltersvik) Progress 1998: Studies of B-cell activity in tonsils and peripheral blood of HIV patients is being summarized in one article. Studies of cytokine production at the single cell level is in the writing phase.

• T cell phenotypes and apoptosis in HIV infected tonsillar tissue (Åsjö) Progress 1998: Apoptotic and phenotypic studies are ongoing.

• Immunohistopathology and mucosal/cellular immunity in experimental M. tuberculosis (Phyu/Mustafa) Progress 1998: Work has been finished but is also ongoing related to differential function of lung and spleen cells in normal and infected mice (Phyu). Furthermore, phenotypic and functional analysis incl. apoptosis of infiltrating cells during experimental tbc infection is currently studied in mice (Mustafa). A total of 5 papers have been submitted where one is in press.

• Immunohistopathology and apoptosis in oral lichen planus (Neppelberg) Progress 1998: A study of the rate of apoptosis in mucosal biopsies is in the writing phase and is currently being written together as an article.

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PUBLICATIONS from THE BROEGELMANN RESEARCH LABORATORY 1998 •

Bolstad AI, Jonsson R: The role of apoptosis in Sjögren's syndrome. Ann Med Interne 149: 25-29, 1998.

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Brun JG: Calprotectin in inflammatory rheumatic disease - summary of thesis. Scand J Rheumatol 27: 87, 1998.

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Cuida M: Host defence factors in Sjögren’s syndrome with special reference to calprotectin - summary of thesis. Scand J Rheumatol 27: 86, 1998.

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Haga H-J, Hultén B, Bolstad AI, Ulvestad E, Jonsson R: Reliability and sensitivity of diagnostic tests for primary Sjögren´s syndrome. J Rheumatol, in press.

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Haga H-J, Jonsson R: The influence of age on disease manifestations and serological characteristics in primary Sjögren's syndrome. Scand J Rheumatol, in press.

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Haga H-J, Jonsson R: Sjögrens syndrom - en orientering for pasienter (In Norwegian). Norsk Revmatikerforbund, pp.1-31, 1998.

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Halse A-K: Immunologi for odontologistudenter. Bergen 1998, pp. 1-48.

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Halse A-K, Harley JB, Kroneld U, Jonsson R: Ro/SS-A reactive B lymphocytes in salivary glands and peripheral blood of patients with Sjögren's syndrome. Clin Exp Immunol 115: in press, 1999.

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Halse A-K, Tengnér P, Wahren-Herlenius M, Haga H-J, Jonsson R: Increased frequency of IL-6 and IL-10 secreting cells in peripheral blood from patients with primary Sjögren's syndrome. Scand J Immunol, in press.

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Halse A-K, Wahren-Herlenius M, Jonsson R: Ro/SS-A and La/SS-B reactive B lymphocytes in peripheral blood of patients with Sjögren's syndrome. Clin Exp Immunol 115: in press, 1999.

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Heimdal JH, Aarstad HJ, Klementsen B, Olofsson J: Disease stage related in vitro peripeheral blood T-lymphocyte responsiveness in head and neck carcinoma patients. Acta Otolaryngol 118: 887-891, 1998.

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Heimdal JH, Aarstad HJ, Klementsen B, Olofsson J: Ex vivo IL-1β, IL-6, IL-12 and TNF-α responsiveness with monocytes from patients with head and neck carcinoma. Eur Arch Otolaryngol, in press.

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Heimdal JH, Aarstad HJ, Klementsen B, Olofsson J: Peripheral blood mononuclear cell (PBMC) responsiveness in patients with head and neck cancer in relation to tumour stage and prognosis. Acta Otolaryngol, in press.

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Hordnes K: Mucosal immunity to group B streptococci in the female genital tract prospects for development of a mucosal vaccine. Doctoral thesis, Univ of Bergen, submitted. ISBN: 82-7788-053-7.

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Hordnes K, Tynning T, Kvam AI, Bevanger L, Brown TA, Jonsson R, Haneberg B: Cervical secretions in pregnant women colonized rectally with group B streptococci have high levels of antibodies to serotype III polysaccharide capsular antigen and protein R. Scand J Immunol 47: 179-188, 1998.

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Hordnes K, Trovik J, Tynning T, Hanebeg B: Self-sampled and air-dried cervicovaginal secretions can be used for analyses of mucosal antibodies. J Immunol Methods 220: 151-159, 1998.

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Humphreys-Beher MG, Brayer J, Yamachika S, Peck AB, Jonsson R: An alternative perspective to the immune response in autoimmune exocrinopathy: Induction of functional quiescence rather than destructive autoaggression. Scand J Immunol 49: in press, 1999.

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Jonsson R: Tar man godt vare på den eksternt finansierte forskningen ved UiB? På Høyden (internavis for UiB) 6. årgang, nr 2: 6, 1998

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Jonsson R: Interfakultär forskarutbildning på gott och ont. På Høyden (internavis for UiB) 6. årgang, nr 3: 6, 1998

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Jonsson R, Brandtzaeg P, Nerland AH, Haga H-J: Immunopathology of mucous membranes and exocrine glands - Conference summary. Arthritis Rheum 41: 572576, 1998.

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Jonsson R, Frøland K: Broegelmanns Forskningslaboratorium. Innsyn Haukeland Sykehus 4 (6): 10-11, 1998.

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Kroneld U, Jonsson R, Carlsten H, Bremell T, Johannessen AC, Tarkowski A: Expression of the mucosal lymphocyte integrin α E β7 and its ligand E-cadherin in salivary glands of patients with Sjögren's syndrome. Scand J Rheumatol 27: 215218, 1998.

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Loro LL, Vintermyr OK, Johannessen AC, Liavaag PG, Jonsson R: Suppression of Fas receptor and negative correlation of Fas ligand with differentiation and apoptosis in oral squamous cell carcinoma. J Oral Pathol Med 28: in press, 1999.

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Oxford GE, Jonsson R, Olofsson J, Zelles T, Humphreys-Beher M: Elevated levels of human salivary EGF following oral and juxta-oral surgery. J Oral Maxillofac Surg, in press.

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Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB, Stewart CA, Peen E, Jonsson R, Humphreys-Beher MG: Transfer of human serum IgG to NOD.Igµnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren's syndrome. Proc Natl Acad Sci (USA) 95: 7538-7543, 1998.

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Robinson CP, Yamachika S, Bounous DI, Brayer J, Jonsson R, Holmdahl R, Peck AB, Humphreys-Beher MG: A novel NOD-derived murine model for primary Sjögren's syndrome. Arthritis Rheum 41: 150-156, 1998.

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Skarstein K: Autoimmunity and pathogenesis of murine sialadenitis - summary of thesis. Scand J Rheumatol 27: 86, 1998.

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Tadesse A: Organ specific in vivo and in vitro cytokine production in chronic murine tuberculosis; thesis Univ of Bergen 1998. ISBN: 82-7815-011-7

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Tengnér P, Halse A-K, Haga H-J, Jonsson R, Wahren-Herlenius M: Detection of antiRo/SSA and anti-La/SSB autoantibody producing cells in salivary glands from patients with Sjögren's syndrome. Arthritis Rheum 41: 2238-2248, 1998.

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Vandevska-Radunovic V: Neural modulation of inflammatory reactions in rat dental tissues incident to orthodontic tooth movement. Doctoral thesis, Univ of Bergen. ISBN: 82-91424-09-8.

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Vandevska-Radunovic V, Kvinnsland S, Jonsson R: Delayed recruitment of immunocompetent cells in denervated rat periodontal ligament following experimental tooth movement. J Dent Res, in press.

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Aarli Å: Annexin II - an IgG-binding protein with immunosuppressive properties. Doctoral thesis, Univ of Bergen. ISBN: 82-7788-065-0.

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Aarli Å, Matre R: Suppression of immunoglobulin secretion by soluble annexin II. Scand J Immunol 48: 522-526, 1998.

Abstracts Abebe F, Tadesse S, Bjune G, Nerland AH: Evalution of cytokine profiles in experimental tuberculosis in the mouse byquantitative RT-PCR. NBS. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Alagib KEF, Børretzen M, Jonsson R, Haga H-J, Thoen J, Thompson KM, Natvig JB: Rheumatoid factor (RF) in primary Sjögren´s syndrome. Presented at the 29th Annual SSI Meeting, Copenhagen, June 10-14, 1998. Printed in: Scand J Immunol 47: (6) abstr 68, 1998. Alagib KEF, Børretzen M, Jonsson R, Haga H-J, Thoen J, Thompson KM, Natvig JB: Structural comparison of rheumatoid factors (RF) from patients with primary Sjögren´s syndrome, rheumatoid arthritis (RA), and healthy immunized donors (HID). Presented at American College of Rheumatology 62nd National Scientific Meeting, San Diego, Nov 8-12, 1998. Printed in: Arthritis Rheum 41: 9 (suppl) S84, 1998. Alagib KEE, Tengnér P, Levi M, Wahren-Herlenius M, Jonsson R, Thompson K, Natvig JB: Characterization of two human monoclonal antibodies against the Ro52 antigen from a patient with primary Sjögren´s syndrome. Submitted. Alarcon-Riquelme M, ........, Haga H-J, Jonsson R,......Gyllensten UB: Cooperative network on the genetics of systemic lupus erythematosus. Presented at the Fifth International Conference on SLE, Cancun, April 20-25, 1998. Printed in: Lupus 7 (suppl 1): 12, 1998. Bolstad AI, Nakken B, Steine S, Skarstein K, Haga H-J, Jonsson R: Identification of susceptibility genes in Sjögren´s syndrome. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Bolstad AI, Wargelius A, Jonsson R: Detection of polymorphisms in the genes encoding Fas and Fas ligand in patients with primary Sjögren´s syndrome. Presented at American College of Rheumatology 62nd National Scientific Meeting, San Diego, Nov 8-12, 1998. Printed in: Arthritis Rheum, 41: 9 (suppl) S324 1998. Breivik T, Nerland A, Murison R, Jonsson R: Genetically determined and sustained stressinduced differences in neuroendocrine responses influence immune cell recruitment in gingival and periodontal tissues in rats. Presented at the IADR Meeting, Nice, June 24-28, 1998. Feseah A, Tadesse S, Bjune T, Nerland AH: Evaluation of cytokine profiles in experimental tuberculosis in the mouse by quantitative RT-PCR. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Haga H-J, Hultén B, Bolstad AI, Ulvestad E, Jonsson R: Reliability and sensitivity of diagnostic tests in Sjögren´s syndrome. Presented at American College of Rheumatology 62nd National Scientific Meeting, San Diego, Nov 8-12, 1998. Printed in: Arthritis Rheum, 41: 9 (suppl) S329 1998. Haga H-J, Hultén B, Bolstad AI, Ulvestad E, Jonsson R: Sensitivity and reliability of diagnostic tests for primary Sjögren´s syndrome. Presented at the Scandinvian Rheumatology Meeting, Aarhus, June 5-8, 1998. Printed in: Scand J Rheumatol suppl. 108: P110, 1998.

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Haga H-J, Jonsson R: The influence of age on clinical features and laboratory parameters in pirmary Sjögren´s syndrome. Presented at the Scandinvian Rheumatology Meeting, Aarhus, June 5-8, 1998. Printed in: Scand J Rheumatol suppl. 108: P111, 1998. Haga H-J, Jonsson R: The influence of age on clinical features and laboratory findings in primary Sjögren´s syndrome. Presented at the 18th EULAR Workshop for Rheumatology Research, Athens, March 12-15, 1998. Printed in: Clin Exp Rheumatol 16: 234, 1998. Haile J, Bjune G, Nerland AH: Use of Guanidium thiocynate with Silca ceramic beads for the rapid and reliable isolation of mycobacteria RNA. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Halse A-K, Tengnér P, Wahren-Herlenius M, Haga H-J, Jonsson R: Frequency of IFN-g, IL6 and IL-10 secreting cells in peripheral blood from parimary Sjögren´s syndrome patients. Presented at the 18th EULAR Workshop for Rheumatology Research, Athens, March 12-15, 1998. Printed in: Clin Exp Rheumatol 16: 212, 1998. Halse A-K, Tengnér P, Wahren-Herlenius M, Haga H-J, Jonsson R: Increased frequency of IL-6 and IL-10 secreting cells in peripheral blood from primary Sjögren´s syndrome patients. Presented at the 29th Annual SSI Meeting, Copenhagen, June 10-14, 1998. Printed in: Scand J Immunol 47: (6) abstr 76, 1998. Humphreys-Beher MG, Brayer J, Esch TR, Peck AB, Jonsson R, Robinson CP: Transfer of human serum IgG to NOD. Igµnull mice reveals a role for autoantiobodies in Sjögren´s syndrome. Printed in: J Dent Res 77 (special issue B) abstr 2793, 1998. Heimdahl JH, Aarstad HJ, Klementsen B, Olofsson J: Fragment spheroids with squamous cell benign or malignant cell stimulate in vitro autologous monocytes to secrete IL-6 but not TNF-α. Printed in: Head & Neck 20, 456, 1998. Mustafa T, Phyu S, Nerland A, Jonsson R, Nilsen R, Bjune G: A novel mechanism of immune evasion by Mycobacterium tuberculosis. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Nakken B, Steine S, Haga H-J, Jonsson R, Bolstad AI: Identification of susceptibility genes in Sjögren´s syndrome: The candidate gene approach. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Nakken B, Steine S, Jonsson R, Bolstad AI: Screening for mutations in the La-gene of patients with primary Sjögren´s syndrome by fluorescent labeling REF-SSCP technique. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Nakken B, Jonsson R, Bolstad AI: Candidate gene analysis in patients with primary Sjögren´s syndrome: screening for mutations in the Ro-52 gene. Submitted. Nerland AH, Sommerset I, Abebe F, Haile Y, Schaug-Pettersen L, Tadesse S, Jureen R, Jonsson R, Bjune G: Molecular biology of tuberculosis. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Nunes IP, Skår CK, Jensen HB, Jonsson R, Bakken V: Critical antigens of Fusobacterium nucleatum which may play a role in the development of periodontitis. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Omholt K, Halse A-K, Nerland A, Haga H-J, Jonsson R: Distribution of HLA class II alleles in a Norewgian Population of Sjögren´s syndrome patients. Presented at the 29th Annual SSI Meeting, Copenhagen, June 10-14, 1998. Printed in: Scand J Immunol 47: (6) abstr 93, 1998. Phyu S, Tadesse A, Tadesse S, Mustafa T, Jonsson R, Bjune G: Compartmentalized immune responses in the spleens and lungs of chronically Mycobacterium tuberculosis infected mice. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Robinson C, Sundler M, Holmdahl R, Jonsson R, Peck A, Humphreys-Beher M: Creation of primary murine models for Sjögren´s syndrome by replacement of NOD MHC. Printed in: J Dent Res 77 (special issue B) abstr 2794, 1998.

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Robinson CP, Brayer J, Yamachika S, Eschy TR, Peck AB, Stewart CA, Peen E, Jonsson R, Humphreys-Beher M: Transfer of human serum IgG to nonobese diabetic Igµnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren´s syndrome. Presented at American College of Rheumatology 62nd National Scientific Meeting, San Diego, Nov 8-12, 1998. Printed in: Arthritis Rheum 41: 9 (suppl) S354, 1998. Sommerset I, Nerland AH: Construction and screening of a sub DNA expression library containing the open reading frames in ”Region of difference 1” (RD1) of Mycobacterium Tuberculosis. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Steinmoen H, Vågnes KS, Nerland AH, Bolstad AI,Vasstrand EN, Bakken V: Preparation of DNA vaccines encoding antigens of Fusobacterium nucleatuum and Porphyromonas gingivalis.. Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Sundler M, Skarstein K, Kjellén P, Jonsson R, Holmdahl R: The influence of different genes on the development of murine sialadenitis. Presented at American College of Rheumatology 62nd National Scientific Meeting, San Diego, Nov 8-12, 1998. Printed in: Arthritis Rheum 41: 9 (suppl) S326 1998. Tadesse S, Abebe F, Phyu S, Mustafa T, Nerland AH, Bjune G. 1998. TGF-β in primary progressive, latent and reactivated murine tuberculosis. . Presented at the Multidisciplinary 30th Anniversary Meeting NBS, Bergen, Oct 17-18, 1998. Tengnér P, Halse A-K, Wahren-Herlenius M, Haga H-J, Jonsson R: Increased number of IL6 and IL-10 secreting cells in peripheral blood from patients with primary Sjögren´s syndrom. Presented at American College of Rheumatology 62nd National Scientific Meeting, San Diego, Nov 8-12, 1998. Printed in: Arthritis Rheum 41: 9 (suppl) S298, 1998. Aarstad HJ, Heimdal JH, Olofsson J: Prognostic value of in vitro T lymphocyte and monocyte function in patients with head and neck carcinoma. Printed in: Clin. Otolaryngol 23, 476, 1998.

4.

External activity

LECTURES/SEMINARS/OTHER ACTIVITY Roland Jonsson: 7-8/1 Attending course: Animals in medical research, UoB 13/1

Lecture in immunology: "Autoimmunity", for medical students, Faculty of medicine, UoB

20/1

Board Meeting in the Foundation «Health and Rehabilitation», Oslo

27/1

Lecture in oral medicine: "Sjögren's syndrome", Faculty of odontology, UoB

30/1

Invited speaker: «Current understanding of the etiopathogenesis of Sjögren´s syndrome», Western Regional Rheumatology Meeting, Göteborg

31/1

Meeting (Member of Organizing Committee) for «The 100-Year Anniversary of Henrik Sjögren», Jönköping

17/2

Lecture in ENT: "Oral disease" for med stud in course Otolaryngology, Haukeland University Hospital/UoB

21

1 hr

1 hr

1 hr

6/3

Opponent on dr med sci thesis, Karolinska Institute, Stockholm

11/3

Chairing Organizing Meeting on the EU Concerted Action «Sjögren´s syndrome», Athens

12-15/3

Attending and session chairman at «The 18th European Worskhop for Rheumatology Research», Athens

24-26/3

Course leader and organizer with own lectures/presentations «Immunological Methods», Bergen, UoB

19-25/4

Attending the «Fifth International Conference on SLE» and Organising Meeting in EU-project «Genetics of SLE and Sjögren´s syndrome», Cancun, Mexico

4/5

Attending «Basic course for project leaders», UoB

10/5

Course leader jointly with Hans-Jacob Haga: «Sjögrens syndrom» at the XXXIII Nordic Eyephysician Meeting, Bergen

15/5

Organizer of the 2.nd Broegelmann Lecture and, together with HansJacob Haga, Organizer of Workshop on Coordination of Rheumatology Research in Norway, Bergen

29/5

Seminar «Diagnostic Aspects of Sjögren´s syndrome» Department of Otolaryngology/Dept. of ENT, Haukeland Univ Hospital, UoB

3/6

Lecture in Dept. of ENT: "Oral disease" for med stud in course Otolaryngology, Haukeland University Hospital/UoB

10-14/6

Attending the XXIXth Annual Scandinavian Society for Immunology Meeting, Council Meeting and Editorial Board Meeting of Scandinavian Journal of Immunology; Copenhagen

27/8

Lecture in Dept. of ENT: "Oral disease" for med stud in course Otolaryngology, Haukeland University Hospital/UoB

1 hr

4/9

Lectures in «Oral Mucosal and Salivary Gland Disease» for dental students in course Oral Pathology, UoB

3 hr

11/9

Lectures in «Oral Mucosal and Salivary Gland Disease» for dental students in course Oral Pathology, UoB

3 hr

28/9

Presentation of Research on Sjögren´s syndrome, Department of Microbiol and Immunol, Haukeland Univ Hospital, UoB

29/9

Seminar «Autoimmune mukosale lidelser», Dept of ENT, Haukeland Univ Hospital, UoB

9/10

Opponent on dr phil thesis, Univ of Stockholm

29/10

Lecture in ENT: "Oral disease" for med stud in course Otolaryngology, Haukeland University Hospital/UoB

22

2 hr

1 hr

1 hr

10/11

Chairing Organizing Meeting on the EU Concerted Action «Sjögren´s syndrome», San Diego, CA

8-12/11

Attending the Amer College of Rheumatology Meeting in San Diego, CA with both poster and selected oral presentation.

12-14/11 Visit at Oklahoma Medical Research Foundation, Immunology/Rheumatology Research Group, Oklahoma City 20-22/11 Attending NorFA (and EU-BIOMED) project Planning Meeting, Uppsala 3/12

Invited lecture/postgrad. research course in immunology: "Salivary gland inflammation", University of Göteborg

4/12

Invited lecture: "Sjögren´s syndrome – how to organize clinical activities", Department of Rheumatology, Karolinska Sjukhuset

R. Jonsson is currently Chairman of the Study Section/Peer Review Committee for Clinical Research, The Research Council of Norway R. Jonsson is currently Counsilmember of Scandinavian Society for Immunology R. Jonsson has during the year been evaluating research proposals for The Italian Ministry for University and Research, and Fonds zur Förderung der wissenschaftlichen Forschung (Austria) During 1998 R. Jonsson has become a member of and served on Organizing Committees of five International Scientific Meetings: • «The 19th European Workshop for Rheumatology Research», Feb 25-28, 1999, Oslo • «Autoantibodies and Autoimmunity», June 24-27, 1999, Oslo • «The 100-Year Anniversary of Henrik Sjögren», Sept 3-5, 1999, Jönköping • «The VII International Symposium on Sjögren´s syndrome», Venice, Dec 2-5, 1999 • «ICI-2001 Sponsor Committee Advisory Group», July 22-28, 2001

Anne Isine Bolstad: 5/2 Seminar: Family collection/characterization SLE/SS, Broegelmann Res. Lab. 26/2

Seminar: Candidate gene studies in human SS, Broegelmann Res. Lab.

3/4

Seminar: Sjögren´s syndrome, Center for Molecular Medicine

30/4

Seminar: Gene mapping in murine SS I, Broegelmann Res. Lab.

Spring 98

Seminar: Genetic aspects of autoimmune diseases, Center for Molecular Medicine.

14/5

Seminar: Summary from the First International Conference on Systemic Lupus Erythematosus and Second International Conference on Antibody Penetration into Living Cells, Cancun, Mexico, Center for Molecular Medicine.

23

1/10

Seminar: Gene mapping in murine SS II, Broegelmann Res. Lab.

3/12

Seminar: Report from ACR meeting in San Diego, Broegelmann Res Lab.

10/12

Seminar: Genetic approaches to inflammatory autoimmune disease through familial mediterranean fever, Center for Molecular Medicine

Audun H. Nerland Spring 98: Seminar: Mycobacterieinfeksjoner - zoonotisk potensiale. Fiske-og dyrehelsemøtet 1998. Solstrand Fjord hotell. 03/98

Seminar: Bruk av genteknologi innenfor vaksineutvikling. Høgskolen i Hedmark, mars 1998.

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