Immune complexes in primary biliary cirrhosis contain mitochondrial antigens

Penner, Edward; Goldenberg, Hans; Albini, Boris; Weiser, Milton M.; Milgrom, Felix

doi:10.1016/0090-1229(82)90056-3

Cited by 18 publications

(4 citation statements)

References 20 publications

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“…This could be possible through two mechanisms. First, IgM as well as IgG3 AMAs may form immune complexes with mitochondrial antigens, as previously reported (18), and activate complement. Second, the unusually immunoreactive IgM present in PBC sera which behaves like immune complexes (19) may be composed of IgM AMAs.…”

Section: Isotype Distributionmentioning

confidence: 81%

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

et al. 1988

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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 1:10(3) or higher; 32% of these patients possessed titers of 10(4), 29% at 10(5) and 7% at 10(6). IgM antimitochondrial autoantibodies were next most prevalent; 63% of the patients were positive and 50% of these patients showed titers of 10(3), 43% at 10(4) and 6% at 10(5). 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Isotype Distributionmentioning

confidence: 81%

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

et al. 1988

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“…There is an unconfirmed report that immune complexes in PBC contain M2 antigens [66]. PBC shows some of the clinical features (e. g. arthralgias, rash) of an autoantigen-related immune complex disease of which SLE is the prototype.…”

Section: Immune Complexesmentioning

confidence: 99%

Primary biliary cirrhosis: Considerations on pathogenesis based on identification of the M2 autoantigens

Mackay

Gershwin

1990

Springer Semin Immunopathol

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“…The availability of specific antibody against an epitope(s) on the 70 kd protein should now indicate whether this protein or a cross-reactive antigen is exposed on the surface of biliary epithelium. Cross-reactivity between biliary epithelium and mitochondrial autoantigens and circulating immune complexes of antibody with mito-150 GERSHWIN, COPPEL AND MACKAY HEPATOLOGY chondrial antigens have been reported (68)(69)(70)(71). Nonetheless, the data appear difficult to interpret, primarily due to the relatively crude methods used to characterize the antigens.…”

Section: The Role Of Autoantigens In the Etiology And Pathogenesis Ofmentioning

confidence: 99%

Primary biliary cirrhosis and mitochondrial autoantigens—insights from molecular biology

1988

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Immune complexes in primary biliary cirrhosis contain mitochondrial antigens

Cited by 18 publications

References 20 publications

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

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

Primary biliary cirrhosis: Considerations on pathogenesis based on identification of the M2 autoantigens

Primary biliary cirrhosis and mitochondrial autoantigens—insights from molecular biology

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