HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus : correlation with clinical and autoantibody subsets

The etiopathogenesis of systemic lupus erythematosus (SLE) is complex and still largely unknown. Genetic, environmental, and hormonal factors contribute to disease susceptibility (1). The importance of genetic factors is documented by 1) the pronounced difference in concordance rates between monozygotic and dizygotic twins (15); 2) the higher disease prevalence in relatives of patients with SLE (14); 3) the higher prevalence of SLE in certain ethnic groups, like African Americans and some Native Americans (18); and 4) studies of murine SLE showing that some strains invariably develop the disease (23,24). In humans, several genes contribute to lupus susceptibility. Their identification has been complicated by the fact that SLE is a heterogeneous disease, both clinically and immunologically (3); in addition, many of the susceptibility genes differ across the various populations (27), and it is well recognized that genetic predisposition is linked to autoantibody repertoires and to clinical subsets of disease (9,20,31). Many studies have focused on human leukocyte antigen (HLA) genes, mainly because they are involved in immune recognition and response, even if genetic susceptibility to SLE is in part located outside the short arm of the sixth chromosome (13,22,30,33,35,36). Studies performed by genomic scan of multiplex lupus families confirm the pathogenetic role of the HLA system in this disease (19). We decided to approach the problem of HLA-SLE association in a large sample of patients, all of Caucasian origin, to enable study of homogeneous subsets defined clinically and serologically. In this paper, we present the results of an immunogenetic study conducted in a large series of European SLE patients. Our objective was to determine the HLA class II allele association with SLE and its main clinical and autoantibody subsets.