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Human NK cells express multiple receptors that interact with HLA class I molecules which, in turn, suppy peptides that bind HLA-E to form CD94/NKG2A NK receptor ligands. These peptides correspond to -22 to -14 residues in the leader sequences of HLA-A, HLA-B and HLA-C binding to the HLA-E site. Methionine – 21 delivers functional peptides in stark contrast to threonine – 21 which does not. This functional dimorphism allows for division into three groups: -21M/M, -21M/T and -21T/T with respectively decreasing potency of the NKCD94/NKG2A+ receptor. Dr. Chandran et al aimed to determine if these particular haplotypes served as differences between the connection between the HLA class 1 alleles and Psoriatic disease vs the normal population.
Six hundred and sixty four PsA patients, 1155 PsC (cutaneous only Psoriasis) patients vs 3118 controls were studied. One thousand one hundred and seventy seven PsA patients, 659 PsC patients and 1096 controls were self- reported European ethnicity from a single center cohort in Toronto. SNP2HLA was used represent HLA class 1 alleles. Analyses using logistical regression to determine association between HLA B-21 amino acid polymorphisms and different phenotypes in PsC vs controls, PsA vs controls, and PsA vs PsC. Sex and population stratification were used as covariates. This study used reverse line blot techniques and sequence specific oligonucleotide (SSO) probes to type HLA and all analyses were conditioned on HLA B27.
This study found that the PsC patient cohort had significantly lower prevalence of -21M compared to PsA and control patients.
In conclusion, this is one study that indicates a potential NK cell pathogenesis in the development of PsA and shows a possible genetic marker that can differentiate PsA from PsC.
Chandran V, Li Q, Machhar R, Abji F, Ye JY, Nair R, Stuart P, Oikonomopoulou K, Elder JT, Gladman DD, Rahman P. −21 HLA-Class I Dimorphism Differentiates Psoriatic Arthritis (PsA) from Psoriasis without Psoriatic Arthritis (PsC) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/%e2%88%9221-hla-class-i-dimorphism-dif.... Accessed October 18, 2018.