Genetic HLA associations in complex regional pain syndrome with and without dystonia

We previously showed evidence for a genetic association of the human leukocyte antigen (HLA) system and complex regional pain syndrome (CRPS) with dystonia. Involvement of the HLA system suggests that CRPS has a genetic component with perturbed regulation of inflammation and neuroplasticity as possible disease mechanisms. However, it is at present unclear whether the observed association with HLA-B62 and HLA-DQ8 in CRPS patients with dystonia also holds true for patients without dystonia. Therefore, we tested the possible association with HLA-B62 and HLA-DQ8 in a clinically homogeneous group of 131 CRPS patients without dystonia. In addition, we investigated the possible association with other alleles of the HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci. We showed an increased prevalence of HLA-DQ8 (molecularly typed as HLA-DQB1*03:02; OR = 1.65 [95% CI 1.12-2.42], P = .014) in CRPS without dystonia, whereas no association was observed for HLA-B62 (molecularly typed as HLA-B*15:01; OR = 1.22 [95% CI .78-1.92], P = .458). Our data suggest that CRPS with and CRPS without dystonia may be genetically different, but overlapping, disease entities because only HLA-DQ8 is associated with both. The findings also indicate that distinct biological pathways may play a role in both CRPS subtypes.

This study is the first to replicate a specific HLA region conferring genetic risk for the development of CRPS. Moreover, associations of HLA-DQ8 with both CRPS with and CRPS without dystonia, and HLA-B62 only with CRPS with dystonia, suggest that these disease entities may be genetically different, but overlapping.