Increased Serum Concentration of IgA2 Subclass and IgA2/IgA1 Ratio: Specific Markers of Chronic Alcoholic Abuse?

Meillet, D; Labrousse, F; Benoit, M; Hernvann, Alain; Musset, Lucile; Amerongen, Geert van

doi:10.1515/cclm.1997.35.4.275

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…Patients with chronic alcoholic liver disease often show high serum IgA levels compared with healthy individuals 15. The immunoblots performed for control of a non-specific binding of bacterial cell material from H hepaticus and H pylori showed no visible IgA reactivity (data not shown).…”

Section: Resultsmentioning

confidence: 91%

Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease

Nilsson

Lindgren²,

Eriksson³

et al. 2000

Gut

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Background-Bile tolerant helicobacter species such as H hepaticus and H bilis have frequently been reported to cause hepatitis in mice and other rodents. Aims-To investigate the possible pathogenic role of these and other helicobacter species in chronic liver disease in humans. Methods-Serum samples from 144 patients with various chronic liver diseases, 30 patients with primary sclerosing cholangitis (PSC), and 48 healthy blood donors were analysed for antibodies against H hepaticus murine strain CCUG 33637 and H pylori strain CCUG 17874. Cell surface proteins of H hepaticus were extracted by acid glycine buVer and used in an enzyme immunoassay (EIA) and immunoblot (IB). Results-56 of 144 (39%) patients with chronic liver diseases and six of 30 (20%) with PSC showed increased antibody concentrations in the H hepaticus EIA; in the H pylori EIA the numbers were 58% and 13% respectively. Compared with the healthy blood donors the antibody reactivity against the two helicobacter species was not increased (46% and 48% respectively). Patient serum samples retested by the H hepaticus EIA after absorption with sonicated H pylori cells remained positive in 12 of 37 (33%) serum samples. Distinct antibody reactivity to 55-65 kDa proteins was observed by H hepaticus IB, after the absorption step, and was considered specific for H hepaticus. These 12 serum samples were from patients with chronic alcoholic liver disease. Conclusions-Antibodies to H hepaticus, often cross reacting with H pylori, occur frequently in patients with chronic liver diseases, with no clear cut relation to specific diagnostic groups. The pathogenic significance of these findings is not known. (Gut 2000;46:410-414)

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Section: Resultsmentioning

confidence: 91%

Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease

Nilsson

Lindgren²,

Eriksson³

et al. 2000

Gut

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“…The factors responsible for the elevated levels of serum IgA in these disorders remain to be elucidated. In ALD, changes in subclass distribution and molecular form of IgA and in the deposition of IgA in various tissues have been reported (2,(5)(6)(7). Aberrant IgA glycosylation and defective clearance from plasma by the liver are implicated in the pathogenesis of IgAN (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

The N-Glycans Determine the Differential Blood Clearance and Hepatic Uptake of Human Immunoglobulin (Ig)a1 and Iga2 Isotypes

Rifai

Fadden

Morrison

et al. 2000

The Journal of Experimental Medicine

144

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Human immunoglobulin (Ig)A exists in blood as two isotypes, IgA1 and IgA2, with IgA2 present as three allotypes: IgA2m(1), IgA2m(2), and IgA2m(n). We now demonstrate that recombinant, chimeric IgA1 and IgA2 differ in their pharmacokinetic properties. The major pathway for the clearance of all IgA2 allotypes is the liver. Liver-mediated uptake is through the asialoglycoprotein receptor (ASGR), since clearance can be blocked by injection of excess galactose-Ficoll ligand and suppressed in ASGR-deficient mice. In contrast, only a small percentage of IgA1 is cleared through this pathway. The clearance of IgA1 lacking the hinge region with its associated O-linked carbohydrate was more rapid than that of wild-type IgA1. IgA1 and IgA2 that are not rapidly eliminated by the ASGR are both removed through an undefined ASGR-independent pathway with half-lives of 14 and 10 h, respectively. The rapid clearance of IgA2 but not IgA1 through the liver may in part explain why the serum levels of IgA1 are greater than those of IgA2. In addition, dysfunction of the ASGR or altered N-linked glycosylation, but not O-glycans, that affects recognition by this receptor may account for the elevated serum IgA seen in liver disease and IgA nephropathy.

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“…5 Both IgA1 and IgA2 subclasses are also elevated in the serum of AC patients. 6 Secretory IgA (SIgA), a product generated by epithelial cells after transcytosis of dimeric IgA and cleavage of the poly-Ig receptor, 7 is also elevated in serum of patients with cirrhosis 1 but not explored in tissues. Factors involved in increased levels of IgA in serum of cirrhotic patients have been explored.…”

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confidence: 99%

Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89–IgA and IgG–IgA complexes: common mechanisms for distinct diseases

Tissandié

Morelle

Berthelot

et al. 2011

Kidney International

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Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1, were detected in the serum of patients with advanced alcoholic cirrhosis. Moreover, aberrant IgA1 formed complexes with IgG and soluble CD89 in serum of patients with advanced alcoholic cirrhosis, similar to those found in primary IgAN. The IgA1 of alcoholic cirrhosis, however, had a modified N-glycosylation, not found in primary IgAN. In patients with alcoholic cirrhosis and IgAN, IgA deposits were associated with CD71 overexpression in mesangial areas, suggesting that CD71 might be involved in deposit formation. Although the IgA1 found in alcoholic cirrhosis bound more extensively to human mesangial cells than control IgA1, they differ from primary IgAN by not inducing mesangial cell proliferation. Thus, abnormally glycosylated IgA1 and soluble CD89-IgA and IgA-IgG complexes, features of primary IgAN, are also present in alcoholic cirrhosis. Hence, common mechanisms appear to be shared by diseases of distinct origins, indicating that common environmental factors may influence the development of IgAN.

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Increased Serum Concentration of IgA2 Subclass and IgA2/IgA1 Ratio: Specific Markers of Chronic Alcoholic Abuse?

Cited by 6 publications

References 23 publications

Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease

Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease

The N-Glycans Determine the Differential Blood Clearance and Hepatic Uptake of Human Immunoglobulin (Ig)a1 and Iga2 Isotypes

Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89–IgA and IgG–IgA complexes: common mechanisms for distinct diseases

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