Major histocompatibility complex class ii gene associations with anti–u1 small nuclear ribonucleoprotein antibody relationship to immunoreactivity with individual constituent proteins

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Abstract
Objective. To better define immunogenetic associations with the anti–U1 ribonucleoprotein (U1 RNP) autoantibody response. Methods. HLA class II alleles were determined by genotyping in 49 Japanese rheumatic disease patients with anti–U1 RNP antibody and 43 race‐matched healthy controls. Immunoreactivities to U1 RNP constituent proteins (70K, A, B/B′, and C) were detected by immunoblots using purified HeLa cell Sm antigen, and antibody titer was determined by passive hemagglutination assay. Results. DQB1*0302 was significantly more frequent in anti–U1 RNP–positive patients than in controls (43% versus 14%; odds ratio [OR] = 4.6, corrected P = 0.03). All anti–U1 RNP–positive patients had either a DQB1*0601, *0602, *0301, *0302, or *0303 allele, which share tyrosine at position 30, and the amino acid sequence Thr, Arg, Ala, Glu, Leu, Asp, and Thr at positions 71–77 in the DQB1 ß1 domain. In contrast, one of these alleles was found in 81% of the controls (OR = 24, P = 0.002). In addition, anti–U1 RNP antibody was associated with unique DQB*0302; DRB1*0401 haplotype. Anti‐70K reactivity and antibody titer were positively associated with a basic amino acid residue, arginine or histidine, at position 13 (DR2 or DR4) and were negatively associated with the amino acid sequence Ile, Leu, Glu, and Asp at positions 67–70, which was present in some of the DR5‐, DR6‐, and DR8‐associated alleles, in the DRB1 ß1 domain. Anti‐C reactivity was strongly associated with DR2, particularly with DRB1*1502. Conclusion. The several shared epitopes located on HLA–DRB1 and DQB1 genes control the anti–U1 RNP autoantibody response.

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