GENETIC PREDISPOSITIONS FOR IMMUNOLOGICAL FEATURES IN CHRONIC LIVER-DISEASES OTHER THAN AUTOIMMUNE HEPATITIS

Background/Aims: Human leukocyte antigens DR3 and DR4 influence suscep tibility for type 1 autoimmune hepatitis and affect its immunological manifestations. We aimed to determine if autoimmune features in patien ts with chronic liver diseases other than autoimmune hepatitis are ass ociated with these same antigens. Methods: One hundred and seventy-eig ht patients were evaluated. Class II typing was performed by restricti on fragment length polymorphism in all patients and 80 normal subjects . Results: One or more autoantibodies, including antinuclear antibodie s (28%), smooth muscle antibodies (8%), thyroid antibodies (18%) and a ntimitochondrial antibodies (13%), were found in 92 patients (52%). Co ncurrent clinical diseases of an immunological nature were recognized in 53 patients (30%). Patients with antinuclear antibodies had a highe r frequency of the A1-B8-DR3 haplotype than patients without these ant ibodies (27% versus 12%, p=0.04) and patients with concurrent immunolo gical diseases had a higher frequency of HLA DR4 than patients without this antigen (51% versus 26%, p=0.003). Patients with antinuclear ant ibodies were more commonly DR3 positive than normals (35% versus 16%, p=0.03) and patients with concurrent immunological diseases were more commonly HLA DR4 positive than normals (51% versus 30%, p=0.02). Concl usions: We conclude that the clinical expression of antinuclear antibo dies is associated with the A1-B8-DR3 haplotype and the presence of co ncurrent immunological diseases is related to the DR4 antigen. These c linical manifestations have a genetic basis that is not disease-specif ic.