Brief Report: HLA-DRB1, DQA1, and DQB1 in Juvenile-Onset Systemic Sclerosis.

Publication Type:

Journal Article


Arthritis & rheumatology (Hoboken, N.J.), Volume 68, Issue 11, p.2772-2777 (2016)


OBJECTIVE: Systemic sclerosis (SSc) is a rare disease that is particularly uncommon in children. Specific HLA alleles have been associated with SSc in adults. This study investigated HLA class II alleles in juvenile onset SSc (jSSc). METHODS: DRB1, DQA1 and DQB1 alleles were determined by DNA-based HLA typing. Analyses were conducted comparing Caucasians with jSSc (n=76) to healthy Caucasians (n=581). RESULTS: Initial analyses focused on HLA class II associations previously reported in adult Caucasians with SSc. DRB1*11 was not significantly increased in jSSc, (22.4% of jSSc vs. 17.6% of controls, OR 1.35, P=0.34), nor were the specific DRB1*11:01 or *11:04 alleles. DQA1*05, a risk factor previously identified in adult SSc males, was increased in jSSc (57.9% vs. 44.1%, OR 1.76, P=0.027), as was DRB1*03 (34.2% vs. 22.5%, OR=1.79, P=0.031). Secondary analyses of all DRB1 allele groups revealed an association with DRB1*10 (10.5% of jSSc vs. 1.5% of controls, OR=7.48, P=0.0002). As this is a new observation, correction was made for multiple comparisons of 13 different DRB1 allele groups; results nevertheless remained significant (P=0.003). Also, a lower frequency of DRB1*01 was observed in jSSc patients who were younger at onset (OR=0.06 P=0.01) and in patients with antibodies to topoisomerase (OR=0.14, P=0.024). CONCLUSIONS: HLA associations with jSSc differed from women with SSc, but were similar to men. Additionally, a novel association with DRB1*10 was observed. The greatest proportion of SSc genetic risk is contributed by the HLA complex and the current study extends the importance of HLA class II genes to children. This article is protected by copyright. All rights reserved.