Anti-mitochondrial antibody IgG subclass distribution and affinity in primary biliary cirrhosis

Abstract

SUMMARYWe have studied the total IgG subclass and anti-mitochondrial antibody (AMA) specific IgG subclass distribution in primary biliary cirrhosis (PBC) sera. In order to solve the problems caused by thc differing affinities of subclass specific monoclonals and the competitive inhibition of antibodies in a whole serum assay. si.\ sera were separated into su be I ass-specific fractions by affinity-depletion chromatography. AMA subclass distribution of 20 further sera from patients with PBC was assessed using conventional methods and thercsultswerecalibratedagainst one of the fractionated sera. Light chain distribution and AMA functional affinity were also assessed for the fractionated subclasses. Total amounts of !gG3 were significantly increased compared with normal controls, AMA were found in all IgG subclasses and not restricted predominantly to lgG3 as previously described. The functional affinity of lgG3 AMA is generally lower as compared with that of other subclasses. No light chain restriction was found.

Autoantibody IgG subclasses to recombinant antigens and the role of bacterial stimuli in primary biliary cirrhosis

“…Previous studies observed that IgG3-AMA were predominant in IIF-AMA-positive PBC sera, [7][8][9][10][11] possibly as a result of the exclusion of IIF-AMA-negative sera. Indeed, the inclusion of a relatively large number of seronegative sera at IIF allowed us to obtain different data, which might also suggest a serological uniqueness of Japanese PBC cases.…”

“…5 All three major Ig classes are found among AMA, with a predominance of IgG and IgM, 6 and several studies have suggested that IgG2 and IgG3 subclasses are predominant in IIF-AMA-positive PBC sera. [7][8][9][10][11] Interestingly, this is in contrast with the common subclass distribution in adult sera where IgG1 account for approximately 66% of IgG. 12 Under normal conditions, IgG subclasses are determined by the target antigen characteristics and the cytokine environment around B cells, with IgG2 predominating in response to polysaccharide antigens 13 and IgG3 to proteins.…”

“…PRIMARY BILIARY CIRRHOSIS (PBC) is characterized by the high specificity of serum antimitochondrial antibodies (AMA) 1 detected by indirect immunofluorescence (IIF), although their origin 2,3 and pathogenetic significance 4 remain uncertain while new therapies are being proposed 5 . All three major Ig classes are found among AMA, with a predominance of IgG and IgM, 6 and several studies have suggested that IgG2 and IgG3 subclasses are predominant in IIF‐AMA‐positive PBC sera 7–11 . Interestingly, this is in contrast with the common subclass distribution in adult sera where IgG1 account for approximately 66% of IgG 12 …”

Thyroiditis in Mosul: a clinico-pathological study

“…and 3/17 cases of FLT. This antibody is shared with other autoimmune conditions specifically primary biliary cirrhosis (30,31) and the two conditions are known to coexist (32,33) .Antinuclear antibody, was positive in 2/4 cases of H.T. and 1/17 cases of FLT which was of grade II.…”

Antimitochondrial autoantibodies in anti-glomerular basement membrane disease

“…There is no polyelonal B cell activation in anti-GBM disease [12], and the only other autoantibodies known to be found in a significant proportion of cases are anti-neutrophil cytoplasm antibodies (ANCA) [ 13]. We were therefore surprised to observe signifieant binding to PDH in a number of anti-GBM sera used as controls in an ELISA that we developed for AMA [14]. The series of experiments reported in this study were designed to assess the extent and specificity of this phenomenon.…”