Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis

Author(s)

Dellavance, Alessandra ^{[1, 2]} ; Cancado, Eduardo Luiz R. ^{[3, 4]} ; Abrantes-Lemos, Clarice Pires ^[4] ; Harriz, Michelle ^[5] ; Marvulle, Valdecir ^[6] ; Andrade, Luis Eduardo C. ^{[1, 2]}

Affiliation

^[1] Fleury Med & Hlth Labs, Div Res & Dev, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, UNIFESP, Div Rheumatol, BR-04023900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Gastroenterol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Trop, Lab Med Invest LIM 06, Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, UNIFESP, Hosp Servidor Publ Estadual Francisco Morato Oliv, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, UNIFESP, Dept Stat, Sao Paulo - Brazil

• Document type: Journal article
• Source: HEPATOLOGY INTERNATIONAL; v. 7, n. 2, p. 775-784, JUN 2013.
• Web of Science Citations: 12

Abstract

To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease. A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA {[}antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA. High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060). The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals. (AU)