Psoriatic Arthritis: HLA Genotype Tracks With Severity

Ricki Lewis, PhD

October 14, 2014

Different combinations of variants (alleles) in the human leukocyte antigen B (HLA-B) and HLA-C gene complexes predict, in an additive fashion, sites of inflammation as well as severity of psoriatic arthritis, according to a study published online September 26 in the Annals of Rheumatic Disease.

Psoriatic arthritis is a phenotypically heterogeneous condition. Muhammad Haroon, MD, from the Department of Rheumatology, St. Vincent’s University Hospital, Dublin, Ireland, and colleagues compared pairwise combinations of alleles that individually are associated with specific clinical characteristics of the disease in 282 patients.

The genes of the major histocompatibility complex encode the HLAs, which control many aspects of immune function. Scientists have recognized for decades links between different HLA allele combinations, which are called haplotypes when on the same chromosome, and an increased risk for certain medical conditions .

In the current study, Dr. Haroon and colleagues determined propensity scores for eight psoriatic arthritis features, based on a polygenic (continuously variable) model to distinguish mild, moderate, or more severe disease.

The findings associated severe psoriatic arthritis with haplotypes B*27:05:02-C*02:02:02, B*08:01:01-C*07:01:01, and B*37:01:01-C*06:02:01, but not with haplotypes B*27:05:02-C*01:01:01 or B*57:01:01-C*06:02:01. Milder disease was associated with B*44 haplotypes, which was consistent with their link to decreased frequency of enthesitis, joint fusion, joint deformities, and dactylitis in univariate analysis.

For patients with symmetrical sacroiliitis, the B*27:05:02-C*02:02:02 haplotype (26.3% vs 5.3%; odds ratio [OR], 6.3) and B*27:05:02-C*01:02:01 haplotype (31.6% vs 7.2%; OR, 6.0) were significantly increased compared with patients in this cohort without this symptom. Haplotype HLA-C*06:02:01 was negatively associated with asymmetrical sacroiliitis.

Enthesitis was positively associated with haplotype B*27:05:02 (28.1% vs 9.7%; OR, 3.7) compared with patients who did not have it. However, two other HLA haplotypes influenced the degree of positive association. Haplotype B*44:03:01-C*16:01:01 was associated with significantly lower risk for enthesitis.

Joint deformity was present in 75.5% of patients with B*08:01:01-C*07:01:01 haplotypes (42.1% vs 25%; OR, 2.3) and was not associated with B*27:05:02 haplotypes. The B*44:03:01-C*16:01:01 haplotype was associated with a significant decrease in the likelihood of joint deformity (3.3% vs 12%; OR, 0.24).

Joint fusion was positively associated with B*08:01:01-C*07:01:01 haplotypes and negatively associated with B*44:02:01-C*05:01:01 and B*44:03:01-C*16:01:01 haplotypes.

The authors note that the exploratory nature of the study and its restriction to Irish patients may limit its clinical use.

Dr Haroon received funding from Abbvie. One coauthor received honoraria and grant support and has been on the advisory boards of Pfizer, Abbvie, MSD, Roche, UCB, Janssen, and Cellgene.

Ann Rheum Dis. Published online September 26, 2014. Abstract

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