Background/Purpose: The association between human leukocyte antigen (HLA) class I alleles and psoriatic disease indicates a potential role for the innate immune system in disease pathogenesis. HLA class I educates NK cells through interactions with killer cell Immunoglobulin receptors (KIRs) and by supplying peptides that bind HLA-E to form ligands for the more conserved CD94/NKG2A NK receptors. The peptides corresponding to residues −22 to −14 of the leader sequence of HLA-A, HLA-B, and HLA-C specifically bind to the binding site of HLA-E. In ~80% of HLA-B allotypes, methionine at position −21M (21M) is replaced by threonine. Methionine −21 delivers functional peptides, whereas threonine at this position (−21T) does not. This functional dimorphism divides the human population into three groups: −21M/M, M/T, and T/T, with decreased order of potency of the NK CD94/NKG2A+ receptor. We aimed to determine whether the distribution of the M and T haplotypes differed between patients with PsA, PsC and healthy controls.

Methods: Two sets of cohorts were included in this study: (a) A discovery cohort of 664 PsA patients, 1155 PsC patients and 3118 controls. Class I HLA alleles were imputed using SNP2HLA. Logistic regressions were used to obtain the association p values by PLINK. We performed three association analyses between HLA B -21 amino acid polymorphisms and different phenotypes: 1) PsC vs. controls; 2) PsA vs. controls; 3) PsA vs. PsC. Population stratification and sex were controlled by including the top seven principal components and sex as covariates in logistic regression. (b) A replication cohort of 1177 PsA patients, 659 PsC patients and 1096 controls with self reported European ethnicity from a large well-phenotyped single centre cohort. HLA typing was done by sequence specific oligonucleotide (SSO) probes using the reverse line blot technique with ambiguous results resolved using sequence specific primers (PCR-SSP). Association analyses as with the Discovery cohort were repeated. All analyses were conditioned on HLA-B*27.

Results:

PsC patients within our discovery cohort had a significantly lower prevalence of -21M compared to controls as well as those with PsA (Table 1). The results of the replication study showed similar results (Table 2).

Conclusion: The study provides indications for a potential role of NK cells in PsA pathogenesis, as well as provides a genetic marker that differentiates PsA from PsC.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/%e2%88%9221-hla-class-i-dimorphism-differentiates-psoriatic-arthritis-psa-from-psoriasis-without-psoriatic-arthritis-psc/