PRIMARY BILIARY-CIRRHOSIS - HIGH PROPORTIONS OF B-CELLS IN BLOOD AND LIVER-TISSUE PRODUCE ANTIMITOCHONDRIAL ANTIBODIES OF SEVERAL IG CLASSES

Anti-mitochondrial Abs (AMA) of the M2 type are recognized as being sp ecific for primary biliary cirrhosis (PBC). We developed a highly spec ific assay to detect single AMA-producing cells using pyruvate dehydro genase (PDH), the major Ag for AMA. Total Ab and AMA production of in vivo activated B cells was measured in peripheral blood from 13 PBC pa tients, 22 patients with other liver diseases, and 15 healthy controls . Anti-PDH-producing cells, PDH spot-forming cells (PDH-SFC), were det ected in 12 of 13 PBC patients and represented a very high proportion of circulating Ig-producing lymphocytes (9 +/- 8.6%; mean +/- SD). The autoantibodies were mainly of Ige and IgM tg classes. The number of P DH-SFC was positively correlated with the numbers of total Ig-SFC with in each Ig class. An increased number of total IgM SFC in blood was fo und in PBC patients compared with controls, and IgM SFC correlated wit h the elevated serum levels of IgM typical for this disease. Among the lymphocytes extracted from PBC liver tissue (n = 5), we detected PDH- SFC of IgG (range 0 to 33% of total SFC), IgM (0 to 42%), and IgA type s (1 to 30%). IgA PDH-SFC were found in five of five livers, but only in two of thirteen blood samples investigated. Taken together, our dat a reveal that very high numbers of B cells spontaneously produce disea se-specific autoantibodies in blood and liver tissue in PBC. Furthermo re, the Ig class distribution of produced autoantibody differs between these two compartments, and this may have pathogenetic significance.