Examination of liver biopsy specimens from 59 patients with alcoholic liver disease and 21 nonalcoholics by immunofluorescence and immunoperoxidase methods using fluorescein-conjugated and peroxidase-labeled antisera against IgA, IgA1, IgA2, and S-IgA showed that 47 of 59 biopsy specimens from alcoholics and 0 of 21 from non-alcoholics showed a "continuous" pattern of IgA and IgA-subclass deposition (P less than 0.001). Grading the intensity of immunofluorescence on 1-4 scale, biopsies with the continuous pattern showed grade 3-4 activity against IgA2 and S-IgA and only grade 1-2 activity against IgA1. Biopsies with the discontinuous pattern showed only grade 1-2 activity against S-IgA, IgA2, and IgA1. Grade 3-4 activity was persistent in all the 47 specimens with the continuous pattern, despite pretreatment with blocking anti-IgA1, whereas 20 and 38 biopsies showed the same activity after blocking with anti-IgA2 and anti-S-IgA sera, respectively. It is concluded from these studies that IgA2 subclass formed a major subclass component contributing to the continuous pattern of IgA deposition in hepatic tissues and that the major source for this IgA in alcoholics was probably derived from the gastrointestinal tract.
Observations in 136 liver biopsies from patients with alcoholic and nonalcoholic liver diseases reveal that IgA deposition in liver tissues appears to have a high degree of morphologic specificity for alcohol injury. Using a direct immunofluorescence technic with fluorescein-conjugated anti-IgG, anti-IgA, anti-IgM, and anti-C1q, four different staining patterns are recognized. These are labelled as "continuous," "discontinuous," "granular," and "pericellular" types depending on their morphologic characteristics and distribution patterns. Fifty of 64 biopsies from alcoholics showed a "continuous" pattern of anti-IgA activity while only three of 72 biopsies from nonalcoholics showed a similar pattern (P less than 0.001). A "pericellular" pattern of anti-IgA activity appears to indicate a more aggressive behavior of alcoholic liver disease. "Continuous" and "pericellular" patterns are seen in "chronic active hepatitis of alcoholics" but not in chronic active hepatitis in nonalcoholics. Anti-IgM activity appears to indicate chronicity of the disease process but does not have any specificity.
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