A123: HLA Associations in a Matched Cohort of Juvenile Idiopathic Arthritis Children With and Without Uveitis
Authors: Sheila T. Angeles-Han, Courtney McCracken, Mina Pichavant, Kirsten Jenkins, Lori Ponder, Erica Myoung, Kelly Rouster Stevens, Larry B. Vogler, Christine Kennedy, Steven Yeh, Spencer Cope, John F. Bohnsack, Aimee O. Hersh, Susan D. Thompson, Sampath Prahalad
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Studies have shown that HLA-DRB1*8, 11 and 13 are strong risk alleles for various juvenile idiopathic arthritis (JIA) subtypes. There are few studies investigating the role of HLADRB1 alleles in children with uveitis. Our objective is to determine the association of these alleles with uveitis in a matched cohort of children with JIA and JIAassociated uveitis (JIA-U). We will also explore associations with uveitis complications and the need for antitumor necrosis factor (TNF) agents.



Methods:

We matched children with JIA and JIA-U on race, ethnicity, sex, age at arthritis diagnosis, and JIA subtype. We included Non-Hispanic White (NHW) controls. We performed high-resolution HLADRB1 genotyping. Odds ratios and 95% confidence intervals are presented. In some instances, exact confidence intervals and p-value are provided due to small sample sizes.



Results:

There were 373 controls, 43 children with JIA-U and 48 with JIA of whom 37 were matched. Each matched group had 29 (78.4%) females and 28 children with oligoarticular (6 extended, 22 persistent) and 9 polyarticular rheumatoid factor (RF) negative JIA.



In our matched analysis comparing children with JIA-U and JIA, there was a difference in the frequency of carriage of DRB1*11 (35.1% vs. 18.9%) and both DRB1*11 and DRB1*13 alleles (16.2% vs. 2.7%) which approached significance, reflecting our modest sample size (OR 2.32, p = 0.116 and OR 6.97, p = 0.107, respectively).



In comparison with controls, children with JIA and JIA-U had increased odds of having DRB1*8 (OR 5.54, p < 0.001 and OR 9.00, p < 0.001, respectively) and DRB1*13 (OR 2.38, p = 0.005 and OR 2.40, p = 0.007). Additionally, compared to controls, children with JIA and JIA-U had greater odds of having at least one of the following: DRB1*8, 11 or 13 (OR 4.27, p < 0.001 and OR 5.37, p < 0.001) and DRB1*11 or 13 (OR 2.30, p = 0.006 and OR 2.29, p = 0.010). Only children with JIA-U had increased odds of having DRB1*11 (OR = 2.22, p = 0.024), and carriage of both DRB1*11 and 13 (OR 9.92, p < 0.001).



No increase in allele frequency was noted with regards to ocular complications or the use of anti-TNF agents in children with JIA-U.1


Table 1. Comparison of HLA-DRB1 in children with JIA and JIA-U	HLA Configuration % OR p value	Matched JIA (N = 37) vs JIA-U (N = 37)	JIA (N = 48) vs controls	JIA-U (N = 43) vs controls




NS = not significant




	
DRB1*8	21.6% vs. 27.0%	22.9% vs. 5.1%	32.6% vs. 5.1%	
 	OR 1.34	OR 5.54	OR 9.00	
 	P=NS	P<0.001	P <0.001	
DRB1*11	18.9% vs. 35.1%	18.9% vs. 16.4%	30.2% vs. 16.4%	
 	OR 2.32	OR 1.18	OR 2.22	
 	P=0.116	P=NS	P=0.024	
DRB1*13	54.1% vs. 54.1%	41.7% vs. 23.1%	41.9% vs. 23.1%	
 	OR 1.000	OR 2.38	OR 2.40	
 	P=NS	P=0.005	P=0.007	
DRB1*8, 11 or 13	78.4% vs. 81.1%	75.0% vs. 41.3%	79.1% vs. 41.3%	
 	OR 1.18	OR 4.27	OR 5.37	
 	P=NS	P <0.001	P <0.001	
DRB1*11 or 13	64.9% vs. 62.2%	58.3% vs. 37.8%	58.1% vs. 37.8%	
 	OR 1.12	OR 2.30	OR 2.29	
 	P=NS	P=0.006	P=0.010	
DRB1*11/8	2.7% vs. 5.4%	4.2% vs. 1.1%	4.7% vs. 1.1%	
 	OR 2.06	OR 3.95	OR 4.50	
 	P=NS	P=NS	P=NS	
DRB1*11/13	2.7% vs. 16.2%	2.1% vs. 1.6%	14.0% vs. 1.6%	
 	OR 6.97	OR 1.30	OR 9.92	
 	P=0.107	P=NS	p<0.001	
DRB1*13/8	2.7% vs. 5.4%	2.1% vs. 0.5%	7.0% vs. 0.5%	
 	OR 2.06	OR 3.95	OR 13.91	
 	P=NS	P=NS	P=0.009	



Conclusion:

This is the first matched analysis of children with JIA and JIA-U. Carriage of both DRB1*11 and 13 appear to increase the risk for developing uveitis. Further studies should be conducted in a larger matched cohort of children with JIA, and the role of HLA in the risk for ocular complications and severe disease should be considered.