GI & Liver Disease Testing By Doctors For Doctors

Updated September 2013

GI & Liver Disease Panels Autoimmune GI Panels Inflammatory Bowel Disease Panel RDL’s Inflammatory Bowel Disease (IBD) Panel combines two valuable diagnostic autoantibody markers: Anti-Saccharomyces cerevisiae Ab (ASCA) and atypical Perinuclear Antineutrophil Cytoplasmic Ab (atypical P-ANCA). ASCA antibodies (IgA & IgG) are the most sensitive for Crohn’s Disease (CD) when atypical P-ANCA is negative, with a sensitivity of 55% and a specificity of 93%. Atypical P-ANCA antibodies have a sensitivity of 51.3% and a specificity of 94% for Ulcerative Colitis (UC) when ASCA is negative. For differentiating between IBD and non-IBD, the presence of either atypical P-ANCA or ASCA antibodies has a sensitivity of 62.6% and a specificity of 92.6%. Atypical P-ANCA is superior to ASCA for identifying IBD. However, atypical P-ANCA can be detected in CD and ASCA can be detected in UC in up to 20% of cases. Pancreatic antibody (PAB) has a sensitivity of 15-40% with a specificity of approximately 95% for CD. Addition of PAB to ASCA and atypical P-ANCA enhances both the sensitivity and specificity for IBD, and helps differentiate between UC and CD. The addition of Anti-OmpC IgA (Anti-Outer Membrane Protein C), Anti-CBir 1 (bacterial flagellin) and DNAse sensitive P-ANCA to ASCA and the more common formalin fixed atypical P-ANCA does not significantly enhance the predictive value for IBD.

IBD Panel Anti-Saccharomyces cerevisiae Ab (ASCA), IgG Anti-Saccharomyces cerevisiae Ab (ASCA), IgA atypical Perinuclear Anti-Neutrophil Cytoplasmic Ab (atypical P-ANCA) Anti-Pancreatic Ab (PAB) Typical Results in IBD and Related Conditions ASCA, IgG

ASCA, IgA

atypical P-ANCA

PAB

Crohn’s Disease

Positive

Positive

Negative

Positive

Ulcerative Colitis

Negative

Negative

Positive

Negative

Test

IBD can be challenging to diagnose and differentiate from related GI disorders. Our Medical Directors are available to discuss any results.

Celiac Disease Panel, Comprehensive Celiac disease is an autoimmune disorder that occurs in genetically susceptible individuals in response to dietary gluten in wheat, rye and barley. In many Western countries, the disease affects approximately 1% of the population and studies show that the true prevalence of Celiac disease is increasing over time. Classical symptoms include the following: malabsorption, chronic diarrhea, iron deficiency anemia and weight loss. Extraintestinal manifestations include osteoporosis, dermatitis herpetiformis, neurological problems, liver disorders, arthritis and obstetric complications. Celiac disease is also associated with other autoimmune disorders such as Type 1 Diabetes Mellitus and autoimmune thyroid diseases. The gold standard in diagnosing Celiac disease is the presence of histological changes on small bowel mucosal biopsies. However, because of the multifaceted nature of the disease, clinicians use serum antibody testing to assist with diagnosis and, at times, screen for the disease. Sensitivities and Specificities of IgA-class Serologic Tests in Untreated Celiac Disease Test

Sensitivity

Specificity

EMA

80 - 97%

97 - 100%

Anti-AGA-DPG

74 - 98%

90 – 99%

Anti-tTG

85 - 98%

95 – 99%

Anti-Actin Ab, IgA

86 – 93%

81 – 90%

RDL performs Total IgA level testing to detect IgA deficiency. IgA deficiency may cause all IgA antibodies to be absent. The sensitivity of IgG AGA-DPG is 82.3% with specificity of 98.9%. IgG AGA-DPG can be positive in patients with IgA deficiency when the other IgA antibodies are absent, thus improving screening and diagnosis of Celiac disease.

Celiac Disease Panel, Comprehensive Anti-Gliadin Ab-Deaminated Gliadin Peptides (AGA-DGP), IgG Anti-Gliadin Ab-Deaminated Gliadin Peptides (AGA-DGP), IgA Anti-Endomysial Ab (EMA), IgA Tissue Transglutaminase Ab (tTG), Human IgA Anti-Actin Ab, IgA IgA, Total Celiac disease can be challenging to diagnose and differentiate from related intestinal disorders. Our Medical Directors are available to discuss any results.

Gluten Free Panel Our Gluten Free Panel is offered to verify patient compliance with a gluten free diet. If the antibodies decrease or disappear, it suggests the patient is likely in compliance with a gluten free diet. Gluten Free Panel Anti-Gliadin Ab-Deaminated Gliadin Peptides (AGA-DGP), IgG Anti-Gliadin Ab-Deaminated Gliadin Peptides (AGA-DGP), IgA Tissue Transglutaminase Ab (tTG), Human IgA

Autoimmune Liver Disease Panels Autoimmune Hepatitis (AIH) is characterized by chronic, immune mediated inflammation of the hepatocytes. It is found predominantly in middle-aged women and if left untreated, the disease may progress to cirrhosis and end-stage liver disease. The clinical presentation of AIH can be variable and includes asymptomatic elevation of liver aminotransferases, as well as vague symptoms such as fatigue, malaise and arthralgias. The distinction between AIH type I and AIH type II is mainly based on serologies. The classic serologic markers of AIH I are ANA and smooth-muscle antibodies (SMA). SMA antibodies are directed against a few different antigens including actin. Anti-Actin IgG antibodies have been shown to have a sensitivity of 74% for AIH I. High titer SMA has a specificity of 96% but a sensitivity in some studies of only 16%. ANA has a sensitivity of 32% and specificity of 76% and is frequently seen in other chronic liver diseases including alcoholic liver disease. The combination of ANA and SMA provides a robust specificity of 99% but does not greatly improve sensitivity (43%). Anti-SLA (Anti-Soluble Liver Antigen) antibodies are the most specific (up to 100%) for AIH I, with a sensitivity of 10-30% (they can also be seen in AIH II). Atypical P-ANCA has a high prevalence in autoimmune hepatitis of 74-80% but is also found in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. Anti-Chromatin Antibodies are found in 40-50% of people with AIH I but are not very specific. AIH type II (also known as LKM [Anti-Liver/Kidney Microsomal]-positive autoimmune hepatitis) makes up about 4% of all AIH patients. Anti-LC1 (liver-specific cytosol antigen type 1) is also specific to AIH II; it generally occurs in conjunction with anti-LKM but in children it may be a sole presenting autoantibody. AMA (Anti-Mitochondrial Antibodies) occur in 5% of AIH patients in the absence of other biliary features. Total IgG levels can be elevated in AIH and may suggest IgG4-associated AIH with IgG4+ plasma cells found on liver tissue despite having normal IgG4 serum levels. Recent data also shows that Anti-Ribosomal P Antibodies can be found in 9.7% of AIH patients who do not have clinical SLE.

Autoimmune Liver Disease Panel Anti-Nuclear Ab (ANA) Anti-Actin Ab, IgG Anti-Soluble Liver Antigen Ab (SLAg Ab) atypical Perinuclear Anti-Neutrophil Cytoplasmic Ab (atypical P-ANCA) Anti-Liver/Kidney Microsomal I Ab (LKM) Anti-Mitochondrial M2 EP Ab (AMA-M2) Anti-Chromatin Ab IgG, Total Autoimmune Liver Disease can be challenging to diagnose and differentiate from related liver disorders. Our Medical Directors are available to discuss complex results.

Primary Biliary Cirrhosis Panel Primary Biliary Cirrhosis (PBC) is an organ-specific autoimmune disease characterized by chronic progressive destruction of intrahepatic bile ducts with portal inflammation resulting in chronic cholestasis and ultimately fibrosis. Serologic assays are important tools for the recognition and diagnosis of PBC, since many antibodies associated with PBC can be present years before symptoms become evident. PBC typically occurs between the ages of 30 and 65 and affects more women than men by a ratio of 9:1. The range of prevalence for PBC in first-degree relatives is 1.3% to 6.4%. The detection of Anti-Mitochondrial Antibodies (AMA) by IFA has been reported in up to 95% of PBC patients with a specificity of 93%. In addition to AMAs, ANA antibodies are present in about 50% of PBC patients. Two nuclear fluorescence patterns are typically found in PBC on ANA IFA staining: a rim-like pattern resulting from autoantibody reaction with glycoprotein 210 (Gp210) and nucleoporin 62, and a pattern of multiple nuclear dots resulting from a reaction with Sp100 and promyelocytic leukaemia antigen. ELISA testing for Gp210 yields a sensitivity of 16-32%, while ELISA testing for Sp100 has a sensitivity of 21-39%. Both of these antibodies have a very high specificity, typically greater than 99% for PBC, and can detect up to 70% of AMA negative patients. Additionally, these antibodies may indentify a subgroup of patients with a more severe disease course. Other AMA negative patients can have antibodies against major M2 components that are present on ELISA testing (Anti-Mitochondrial M2 EP Antibodies), which also have a specificity of up to 100%. The presence of AMA is highly diagnostic of PBC and predictive of disease occurrence even in asymptomatic patients who do not have cholestasis.

Primary Biliary Cirrhosis Panel Anti-Nuclear Ab (ANA) Anti-Mitochondrial Ab (AMA) by IFA Anti-Mitochondrial M2 EP Ab (AMA-M2) Anti-glycoprotein 210 Ab (anti-gp210 Ab) Anti-sp100 Ab Primary Biliary Cirrhosis can be challenging to diagnose and differentiate from related liver disorders. Our Medical Directors are available to discuss any results.

Clinical Expertise Our Medical Directors are board certified Internists & Rheumatologists. All of our technologists have over 15 years of experience in immunologic testing and interpretation. RDL has performed autoimmune testing in the fields of gastroenterology and hepatology for over twenty years, using FDA approved kits. RDL maintains an extensive serum bank of serologically characterized specimens for all high priority autoimmune markers. We use this repository to validate all test kits used by RDL. RDL has been CAP and CLIA certified since 1978.

Personal Service All test results are reviewed by our Medical Directors who may contact you personally to discuss complex results, and are available for clinical consultation on any test results. Real people answer our phones, so you can get an immediate response to all your questions and concerns. We are a provider for Medicare and Blue Cross/Blue Shield, as well as many other insurances throughout the country, and we can usually adapt to your patient’s insurance. We are sensitive to your patients’ financial concerns, and can offer unique plans to work within their budget.

Cost Effective RDL’s panels are more cost-effective than performing individual tests and provide more comprehensive results. An ANA is performed at no additional cost on all atypical P-ANCA positive samples. RDL offers free courier service throughout the United States.

Please visit our website, www.rdlinc.com, for additional information and references.

September 2013, RDL, Inc.

RDL Reference Laboratory Creative Solutions for Complex Medicine

10755 Venice Boulevard Los Angeles, CA 90034 tel: 310.253.5455

800.338.1918 fax: 310.253.5466 www.rdlinc.com