The predominance of IgG3 and IgM isotype antimitochondrial autoantibodies against recombinant fused mitochondrial polypeptide in patients with primary biliary cirrhosis

C. D. Surh, A. E. Cooper, R. L. Coppel, Patrick S Leung, A. Ahmed, R. Dickson, M. Eric Gershwin

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Autoantibodies against inner mitochondrial membrane proteins are a hallmark of primary biliary cirrhosis. Specifically, these antimitochondrial autoantibodies recognize two polypeptides of approximately 70 and 52 kD, respectively. Although the specificity of antimitochondrial autoantibodies has been studied for the past 2 decades, the complementary DNA encoding the major primary biliary cirrhosis-specific 70 kD antigen has only recently been cloned. The availability of the recombinant autoantigen has resulted in the development of a highly sensitive and specific ELISA to detect antimitochondrial autoantibodies and to determine their immunoglobulin isotypes. We report herein that IgG3 is the predominant isotype of antimitochondrial autoantibodies in a group of 74 primary biliary cirrhosis patients. This finding is significant in light of the genomic immunoglobulin in heavy chain gene arrangement. Ninety-three per cent of primary biliary cirrhosis patients possessed IgG3 antimitochondrial autoantibodies with titers of 1:103 or higher; 32% of these patients possessed titers of 104, 29% at 105 and 7% at 106. IgM antimitochondrial autoantibodies were next most prevalent; 63% of the patients were positive and 50% of these patients showed titers of 103, 43% at 104 and 6% at 105. Other isotypes were present but in much lower titer and occurrence. Isotypes of antimitochondrial autoantibodies reactive to the 52 kD antigen were also determined using immunoblotting techniques. The predominance of IgG3 and IgM were similarly observed. Finally, the serum immunoglobulin isotype levels of primary biliary cirrhosis patients were compared with healthy normal adults by radial immunodiffusion. Serum IgG3 and IgM were very elevated in primary biliary cirrhosis; with IgG3 at 5.5-fold and IgM at 4.3-fold above normals. Moreover, IgG3 comprised an average of 17.4% of the total serum IgG in primary biliary cirrhosis compared to 4.5% in the normal population. These results are noteworthy because experimental and naturally occurring viral infections likewise lead to a predominance of IgG3 antibodies.

Original languageEnglish (US)
Pages (from-to)290-295
Number of pages6
JournalHepatology
Volume8
Issue number2
StatePublished - 1988

ASJC Scopus subject areas

  • Hepatology

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