Predominance of IgG3 subclass in primary cirrhosis.

Riggione, O; Stokes, R P; Thompson, Rachel

doi:10.1136/bmj.286.6370.1015-a

Cited by 19 publications

(9 citation statements)

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“…Additional support for our contention that these individuals do have early PBC is offered by the comparison of IgG subclasses in this group with those in patients with "classical" advanced PBC. We confirmed the findings of Riggione et al (14) that, in classical PBC, the AMA is polyclonal and predominantly in the IgG, and IgG3 subclasses and that there is a relative excess of IgG3 in the serum; an exactly similar abnormality was found in the present asymptomatic, normal LFT patients. We have not attempted to perform an analysis of different AMA subclasses as described by Berg et al (15).…”

Section: Discussionsupporting

confidence: 94%

“…Patients 24 and 28 were mother and daughter (detected independently); no other patients had any relative with PBC. Eight had current or previous thyroid disease (Patients 2, 3 By definition, all patients had normal routine LFTs; however, T-GT was elevated in 14 patient (No. 27) had an estimated daily alcohol consumption of over 10 gm per day.…”

Section: Discussionmentioning

confidence: 97%

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Positive antimitochondrial antibody but normal alkaline phosphatase: Is this primary biliary cirrhosis?

et al. 1986

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Twenty-nine patients with a positive antimitochondrial antibody titer greater than or equal to 1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer greater than or equal to 1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Positive antimitochondrial antibody but normal alkaline phosphatase: Is this primary biliary cirrhosis?

et al. 1986

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“…The increase in serum IgG3 levels and the predominance of IgG3 AMA in PBC are consistent with two previously published reports (12,13). The present results, however, reveal more insight into the isotypes of AMAs.…”

Section: Discussionsupporting

confidence: 93%

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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“…The IgGl to IgG3 ratio was also significantly reduced in PBC. Other researchers have also reported on the IgG3 level in PBC [8][9][10][11]. Bird et al proposed that blood lymphocytes were one source of this subcla~s.~ We confirmed their data, but Bird et al did not examine the other subclasses of IgG.…”

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confidence: 78%

Subclass restriction of immunoglobulin G in liver cirrhosis

Akbar

Onji

Masumoto

et al. 1990

J of Gastro and Hepatol

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The serum immunoglobulin G (IgG) subclasses were determined in 41 patients with liver cirrhosis (LC) and in 15 normal controls. In 19 cases of LC and in 6 normal controls, the IgG subclasses were also determined in lymphocyte culture supernatants. The determinations were performed by enzyme immunoassay. It was found that the absolute mean IgG1 and IgG3 levels were increased in all LC due to various causes. The mean IgG1 increase was most pronounced in post-hepatitic LC, and the mean percentage of IgG1 to total IgG was also increased in this type of LC in comparison with the normal controls and the other types of LC. The IgG3 fraction was significantly increased in primary biliary cirrhosis (PBC). In alcoholic LC, all IgG subclasses were increased significantly in comparison with normal controls. In lymphocyte culture supernatants from PBC patients, the mean IgG1 and IgG3 levels were increased in supernatants from unstimulated cultures, and the mean IgG1, IgG3, and IgG4 were increased after pokeweed mitogen (PWM) stimulation. In post-hepatitic LC, the mean IgG4 level was increased in both unstimulated culture supernatants and after PWM stimulation. In alcoholic LC, the mean IgG4 level was increased in unstimulated culture supernatants, whereas the mean IgG1 level was increased after PWM stimulation. These findings showed that LC of differing aetiologies exhibited different profiles of IgG subclasses. This may be related to the different aetiological agents and the pathogenesis of the different types of LC.

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Predominance of IgG3 subclass in primary cirrhosis.

Cited by 19 publications

References 0 publications

Positive antimitochondrial antibody but normal alkaline phosphatase: Is this primary biliary cirrhosis?

Positive antimitochondrial antibody but normal alkaline phosphatase: Is this primary biliary cirrhosis?

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

Subclass restriction of immunoglobulin G in liver cirrhosis

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