Psoriatic dactylitis: the association with HLA genetic susceptibility markers.

Abstract

Human leukocyte antigen (HLA) alleles, particularly of HLA-B and HLA-C, are associated with the susceptibility to and the expression of psoriatic arthritis (PsA). We aimed to identify HLA alleles and haplotypes associated with dactylitis and the time to resolution of tender dactylitis. We retrieved longitudinal data on 1216 patients with PsA followed at an observational cohort. We screened HLA-B and -C alleles with >5% frequency in our sample for association with dactylitis by employing logistic regression fitted using generalised estimating equations. We also analysed common haplotypes. We then used Cox regression, adjusted for confounders, to explore the association between these alleles and haplotypes with the time to resolution of the first tender dactylitis episode. Dactylitis was observed in 584 (48%) patients over a median follow-up of 12.0 years (IQR: 5.7-20.1). HLA-B*27 (odds ratio [OR] 1.94, 95% CI 1.49-2.53), HLA-C*02 (OR 1.63, 95% CI 1.17-2.25), and HLA-B*27/C*02 (OR 1.88, 95% CI 1.32-2.67) were associated with a higher risk of dactylitis, whereas HLA-B*15 was associated with a lower risk (OR 0.72, 95% CI 0.54-0.98). A weaker association was observed for HLA-C*12 (OR 1.25, 95% CI 0.97-1.62) and HLA-B*27/C*01 (OR 1.40, 95% CI 0.99-2.00). Notably, HLA-B*27 was associated with slower resolution of tender dactylitis (hazard ratio 0.74, 95% CI 0.57-0.96). HLA-B*27 and -C*02 and the HLA-B*27/C*02 haplotype are associated with PsA dactylitis. HLA-B*27 may also influence the resolution of tender dactylitis. These alleles are thus associated with PsA dactylitis susceptibility and severity; replication studies are required.