Circulating IgA immune complexes and skin IgA deposits in liver disease relation to liver histopathology

Alcoholic liver disease (ALD) is characterized by elevated serum IgA concentrations, the presence of circulating immune complexes containing IgA, and IgA deposits along sinusoids in the liver. When combined with the presupposed IgA-clearance function of the liver, a causal association between IgA abnormalities and the liver disease in ALD can be suggested. This prompted us to study the presence and concentration of circulating IgA-containing immune complexes (IgA-CIC) in 41 patients with ALD and 41 patients with other nonalcoholic liver diseases having comparable serum IgA levels. We searched for relationships among IgA-CIC and history of alcohol abuse, liver histopathology, and IgA deposits in the liver. Using an anti-IgA inhibition binding assay, 56% of the patients exhibited IgA-CIC in polyethylene glycol precipitate of serum and 38% showed IgA-CIC in whole serum. The prevalence and concentration of IgA-CIC was lowest in cases with nonspecific changes or steatosis in the liver biopsy and highest in cases with hepatitis or cirrhosis (P < 0.01). The occurrence of IgA-CIC was not related to a history of alcohol abuse or to the presence of IgA deposits along hepatic sinusoids (which occurred in 78% of ALD and 20% of non-ALD cases). A skin biopsy was available from 34 patients (19 with ALD and 15 with non-ALD). In 68% of these biopsies, IgA deposits were observed in superficial blood capillaries. The presence of skin IgA deposits was related to that of IgA-CIC detected in whole serum (P < 0.05): there was no significant relationship with liver histopathology, alcohol abuse, or the presence of IgA deposits in the liver. We conclude that the presence of circulating IgA-CIC is directly related to the severity of liver parenchymal damage, irrespective of an alcohol etiology. This conclusion substantiates the pivotal role of the liver in the clearance of circulating IgA, especially of IgA-CIC.Supported in part by the Alcohol Fonds, The Hague, The Netherlands.