title: Mucosal immunity and primary biliary cirrhosis: presence of antimitochondrial antibodies in urine.
abstract: We have shown that IgA-class antimitochondrial autoantibodies (AMA) can be detected in the bile and saliva of patients with PBC, suggesting that AMA are secreted into the luminal fluid across bile ducts and salivary glands. These data prompted us to determine whether AMA of the IgA isotype may be transported across other epithelial mucosa. Therefore, we tested for the presence of AMA in the urine specimens of 83 patients with PBC and 58 non-PBC controls including healthy individuals and patients with other liver diseases. Patients enrolled in this study had no history of renal disease, and we confirmed there was less than 50 microgram/mL of protein in each of the urine specimens. Interestingly, we found that AMA were present in the urine of 71/83 (86%) of all patients with PBC and in 71/78 (91%) of patients with PBC that were serum AMA positive. In contrast, AMA were not detected in any of the 58 control urine specimens. Of particular interest, AMA of the IgA isotype was present in 57/83 (69%) of patients with PBC, and in 52 of these 57, we found secretory-type IgA. In a nested random subgroup of urine samples, the prevalence of the IgA2 AMA was 6/18 (33%), significantly lower than in matched serum samples, 13/16 (81%, P =.007). These data show that AMA of the IgA isotype is secreted into urine from the uroepithelium of patients with PBC, and support the thesis that PBC originated from either a mucosal challenge or a loss of mucosal tolerance.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, School of Medicine, Davis, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: G
authors.initials: G
authors.lastname: Nalbandian
authors.forename: P S
authors.initials: PS
authors.lastname: Leung
authors.forename: G D
authors.initials: GD
authors.lastname: Benson
authors.forename: S
authors.initials: S
authors.lastname: Munoz
authors.forename: J A
authors.initials: JA
authors.lastname: Findor
authors.forename: A D
authors.initials: AD
authors.lastname: Branch
authors.forename: R L
authors.initials: RL
authors.lastname: Coppel
authors.forename: A A
authors.initials: AA
authors.lastname: Ansari
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000737:chemistry / Q000145:classification / Q000652:urine*; D001324:Autoantigens / Q000652:urine; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007109:Immunity; D007070:Immunoglobulin A / Q000276:immunology / Q000652:urine; D007074:Immunoglobulin G / Q000652:urine; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology* / Q000652:urine*; D008928:Mitochondria / Q000276:immunology*; D020033:Protein Isoforms / Q000652:urine; D011507:Proteinuria / Q000652:urine; D019459:Urothelium / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D020033:Protein Isoforms