The serological hallmark of primary biliary cirrhosis is the presence of pyruvate dehydrogenase complex E2 subunit antimitochondrial antibodies.
Anti-pyruvate dehydrogenase complex E2 antibodies cross-react specifically with mycobacterial hsp65.
Dr Diego Vergani and colleagues demonstrated that the motif SxGDL[ILV]AE shared by pyruvate dehydrogenase complex E2212-226 and hsp's is a cross-reactive target.
The research team found that this same motif is present only in ß-galactosidase of Lactobacillus delbrueckii.
| ß-galactosidase266-280 was found in 52% of antimitochondrial antibodies-positive patients
The team hypothesized that this homology would also lead to cross-reactivity.
The researchers tested the mimics via ELISA for reactivity and competitive cross-reactivity.
Sera was used from 100 antimitochondrial antibodies-positive and 23 antimitochondrial antibodies-negative primary biliary cirrhosis patients and 190 controls.
The team also tested an Escherichia coli pyruvate dehydrogenase complex E2 mimic that has been pathogenetically linked to primary biliary cirrhosis but lacks this motif.
The team found that anti- ß-galactosidase266-280 of Lactobacillus delbrueckii antibodies were restricted to 57 % of antimitochondrial antibodies-positive patients.
The researchers noted that anti- ß-galactosidase266-280 of Lactobacillus delbrueckii belonged to immunoglobulin G3.
The team also found that 12% of the controls had anti- ß-galactosidase266-280 antibodies, mainly of the immunoglobin G4 subclass.
The researchers observed that Escherichia coli pyruvate dehydrogenase complex E2 reactivity was virtually absent.
ß-galactosidase266-280 or pyruvate dehydrogenase complex E2212-226 reactivity of the immunoglobin G3 isotype was found in 52% of antimitochondrial antibodies-positive patients vs 1 control.
The team confirmed, via competition ELISA, Lactobacillus delbrueckii ß-galactosidase266-280 or pyruvate dehydrogenase complex E2212-226 reactivity was due to cross-reactivity.
The research team observed that antibody affinity for ß-galactosidase266-280 was greater than for pyruvate dehydrogenase complex E2 mimics.
In addition, the team noted that preincubation of a multireactive serum with ß-galactosidase266-280 reduced the inhibition of enzymatic activity by 40%.
However, only 12 % marginal effects or 2 % with no effect was observed in human or Escherichia coli pyruvate dehydrogenase complex E2 mimics.
Dr Vergani's team concludes, “Immunoglobin G3 antibodies to ß-galactosidase of Lactobacillus delbrueckii cross-react with the major mitochondrial autoepitope and are characteristic of primary biliary cirrhosis."