Background/Purpose: Diagnosing psoriatic arthritis (PsA) is challenging, underscoring the importance of discovering novel biomarkers through proteomics for early and accurate detection. Molecular clustering can elucidate disease heterogeneity, facilitating the identification of subtypes and informing personalized treatment strategies. This study aims to discover new proteins involved in PsA pathogenesis and uncover molecular phenotypes of PsA patients through unsupervised analysis.

Methods: This study involved 154 participants, including 104 PsA patients (diagnosed by CASPAR criteria) and 50 control subjects with musculoskeletal symptoms but no rheumatic disease. We analyzed 384 proteins in peripheral blood mononuclear cells (PBMCs) using Olink technology, exploring biological functions with the R platform and identifying molecular clusters with a self-organizing map algorithm.

Results: PsA patients had an average disease duration of 7 ± 5 years and moderate disease activity, with elevated acute phase reactants compared to controls. Clinical manifestations included dactylitis, enthesitis, and onychopathy. We detected 338 proteins in PBMCs, with 73 significantly altered in PsA patients, enriched in inflammatory response, immune function, and osteoclast activity. Proteins altered were associated with disease activity and dactylitis. Unsupervised analyses identified three PsA clusters with distinct molecular patterns, involving proteins like DAPP1, CCN2, SPRY2, and others, and different levels of C-reactive proteins and monocytes.  Moreover, we observed differences in the proteomic profile based on the disease duration ( > 5 years or < 5 years).

Conclusion: High-throughput proteomic analysis identified novel protein alterations in PsA related to inflammation, immune response, and osteoclast function. This study revealed distinct molecular clusters tied to clinical features and immune cell types. These findings pave the way for validation studies to confirm these proteins as robust biomarkers, seeking to improve PsA diagnosis.

Acknowledgements. Supported the “Instituto de Salud Carlos III” (PMP21/00119, PI22/00539 and RICOR-RD21/0002/0033) co-financed by the European Union and “Junta de Andalucia” (PI-0243-2022).

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/unveiling-new-molecular-signatures-in-psoriatic-arthritis-using-comprehensive-proteomic-analysis-of-peripheral-mononuclear-cells/