Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its lactobacillus mimic

The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2(212-226) and hsp's is a cross-reactive target. Having found that this same motif is present only in beta-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia coli (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL266-280 1ACDE antibodies were restricted to AMA-positive patients (54 of 95, 57 %) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12 %; P < .001) had anti-BGAL266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL266-280/PDC-E2212-226 reactivity of the IgG3 isotype was found in 52 (52 %) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL266-280/PDC-E2212-226 reactivity was due to cross-reactivity as confirmed via competition ELISA. Antibody affinity for BGAL26G-280 Was greater than for PDC-E2 mimics. Preincubation of a multireactive serum with BGAL266-280 reduced the inhibition of enzymatic activity by 40 %, while marginal effect (12 %) or no effect (2 %) was observed in human or ECOLI PDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.