HLA-DR5 and DQB1*03 Class II Alleles Are Associated With Cutaneous T-Cell Lymphoma

Abstract

Cutaneous T-cell lymphoma (CTCL) may present with eczematous lesions, mycosis fungoides (MF), or as exfoliative erythroderma with circulating atypical cells, Sezary syndrome (SS). The "malignant" T cells are epidermotropic and clonal, but whether they respond to antigen stimulation is unknown. Because CD4+ lymphocytes recognize antigen presented by histocompatibility locus antigen (HLA) class II molecules, and HLA association have been found in autoimmune skin diseases, we determined by allele-specific oligonucleotide typing whether HLA-DR or DQ alleles were associated with CTCL and its two variants MF (n = 47) and SS (n = 23). Phenotypic frequencies were compared by chi-square and Fisher exact test, and p values were corrected independently for either 12 DR or 15 DQ alleles. HLA-DR5, previously associated with MF, was significantly increased in all 70 CTCL patients (31.5%) versus controls (11%) (uncorrected p value [Pnc] = 0.000038, odds ratio [OR] = 3.9, 1.9 < OR < 8.1), in MF patients (34%) (Pnc = 0.000047, OR = 3.62, 1.9 < OR < 10), and in SS patients (26%) (Pnc = 0.03, OR = 3, 0.9 < OR < 9.3). HLA-DQB1*03 alleles (0301, 0302, and 0303) were increased in 72% of all CTCL patients versus 49% of controls (corrected p value [Pc] = 0.014, OR = 2.7, 1.4 < OR < 5.1), in SS (82%) (Pc = 0.05, OR = 4.7, 1.4 < OR < 5), and in MF (67%) (Pnc = 0.024, OR = 2.15, 1 < OR < 4.5). DQB1*0502 was strongly increased in SS patients (Pc = 0.045, OR = 7.75, 1.25 < OR < 48). Although HLA-DQB1*0603 and HLA-DR6 (1301, 1302, and 1402) were decreased in all groups, the decreases were not statistically significant. These data suggest that certain HLA-DRB and DQB1 alleles, also associated with other T-cell-mediated skin diseases, may participate in the pathogenesis of or susceptibility to CTCL.