ASSOCIATION BETWEEN CHRONIC CUTANEOUS LUPUS-ERYTHEMATOSUS AND HLA CLASS-II ALLELES

CCLE, a disease entity at the benign end of the lupus spectrum, is cha racterized by marked photosensitivity and skin lesions in sun-exposed areas. The histopathology of lesions resembles hypersensitivity type I V reactions. We have asked whether an association between class II all eles and CCLE exists. RFLP analysis of HLA-DQA genes revealed a Tag I HLA-DQA1 allelic restriction fragment overrepresented in a group consi sting of 26 patients as compared to healthy control individuals. This result was corroborated by typing with oligonucleotide probes. The pre sence of the DQA1()0102 allele in the patients' group led to a relati ve risk of 4.57, with a statistical significance of p < 0.05 after cor rection for 36 comparisons. Although not statistically significant, it is interesting that all patients possess in at least one of their HLA -DQA1 alleles a nucleotide sequence coding for the amino acid glutamin e at position 34 of the DQ alpha molecule. The expected frequency of t hese alleles in the control population amounts to 82%. The HLA-DRB1() 16 allele, which is found in linkage disequilibrium with the HLA-DQA1( )0102 allele, is also observed at an increased frequency in the patie nt's group, though the association was not significant after correctio n for the number of comparisons. However, no association of CCLE with alleles at the HLA-DPB1 locus was found. The association of CCLE with certain HLA class II alleles points to an involvement of HLA-DQ and/or -DR molecules in the pathogenesis of the disease. Alternatively, gene tic loci in linkage disequilibrium may code for elements which contrib ute to the development of CCLE. In conclusion, a genetic marker for CC LE is mapped to the human HLA class II region telomeric of the HLA-DP locus.