Background/Purpose: Psoriatic arthritis (PsA) is a heterogeneous disease with diverse clinical and radiographic manifestations. A number of human leukocyte antigen (HLA) alleles have been found to be associated with PsA.¹ HLA-C*06:02 is associated with severe skin disease and a late onset, milder musculoskeletal phenotype; HLA-B*27:05 with entheseal-based disease, severe musculoskeletal disease, enthesitis, symmetric sacroiliitis (SI) and mild psoriasis; HLA-B*08:01 with synovial-based disease, asymmetric SI, joint deformity, joint fusion and dactylitis while HLA-B*38:01/39:01 is associated with more axial involvement and joint damage progression.² Our hypothesis is that in each of these distinct genetic groups and perhaps as a consequence of the inflammatory events that occur following MHC-peptide interaction, a different pattern of inflammation involving diverse systemic molecules and mediators may be unleashed which in turn determines clinical phenotype and possibly therapeutic response. Our objective is to identify whether there are differences in serum protein expression between groups of patients with specific combinations of HLA genotypes and clinical features.

Methods: Patients with a diagnosis of PsA, fulfilling the CASPAR criteria, aged >18 years were clinically assessed, 10 patients from each of the 4 defined HLA groups. We included a fifth distinct clinical group, Arthritis Mutilans, which as yet has no defined genotype. Serum samples were obtained from all patients. Proteomics Strategy: Serum samples from patients in each of the 5 groups were pooled. Serum pools were depleted of high-abundant proteins. The protein concentration of the remaining low abundant protein fractions was measured and subsequently, protein was digested. Finally, samples were purified prior to liquid chromatography-mass spectrometry LC-MS/MS analysis. Data was imported into MaxQuant and Perseus for quantitative and statistical analysis.

Results: Replicate LC-MS/MS analysis of each the 5 pools (n=3) revealed that a total of 437 proteins could be identified. Of these proteins, 219 were found to be significantly differentially expressed between the different groups (False Discovery Rate: 0.01, p≤ 0.05). Table 1 describes the number of proteins differentially expressed when comparing one PsA subgroup to the other 4 combined groups.

Table1 shows the discovery data analysis summary

Conclusion: In this study, it was possible to identify proteins that were significantly differentially expressed across the 5 PsA phenotypes. Validation strategies are in progress to measure all differentially expressed proteins in individual patient samples using a targeted proteomics approach. This work is an important first step toward the development of a protein biomarker panel that can be used to distinguish between different PsA subgroups. References: 1. Winchester R, et al. A&R64:1134-44, 2012 2. Haroon M, et al. ARD75:155-162, 2016

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differential-serum-protein-expression-in-groups-of-psoriatic-arthritis-patients-characterised-by-specific-hla-genotypes-and-clinical-features/