Association of Human Leukocyte Antigen Polymorphisms With Moderate-to-Severe Dry Eye With and Without Sjögren's Syndrome.

Purpose: Sjögren's syndrome dry eye (SSDE) has been described in relation to human leukocyte antigen (HLA) polymorphisms. It is unknown whether non-Sjögren's syndrome dry eye (NSDE) is related to HLA. This study aimed to evaluate the genetic association of HLA polymorphism with dry eye disease (DED). This was a cross-sectional study.

Methods: Patients with moderate-to-severe DED with and without Sjögren's syndrome (SS) were included. Oral swab samples were collected and HLA genotyping was performed using single-molecule real-time sequencing. The normal healthy population was used as the control group for the susceptibility alleles identification. The signs and symptoms of DED were compared between patients with and without susceptibility alleles.

Results: Sixty-four (64) patients with NSDE (mean age = 47.55 years, 92.2% female) and 40 patients with SSDE (mean age = 52.68 years, 90% female) were included. HLA-B*40:01 allele frequency in the NSDE group was significantly higher than in the reference population (odds ratio [OR] = 2.42, P < 0.001). We identified a trend toward worsening of the ocular surface condition with HLA-B*40:01 carrier. This was manifested by a higher Oxford score (P < 0.0001) and more meibomian gland dropout (P = 0.030) and worse visual acuity (P = 0.006). Further analysis revealed that higher severe rate of NSDE was associated with HLA-B*40:01 carrier status (67.39% vs. 42.68%, P = 0.007). In addition, patients with SSDE showed a significantly higher frequency of HLA-B*40:01, HLA-C*07:02, HLA-DQB1*06:01, and HLA-DRB1*16:02. Patients with SSDE carrying HLA-B*40:01 had less tear secretion.

Conclusions: Significant associations exist between HLA alleles and moderate-to-severe DED. HLA polymorphisms were associated with the clinical features of moderate-to-severe DED, possibly via modulating the ocular surface immune function.