Naïve Inflammatory Proteome Profiles of Glucocorticoid Responsive Polymyalgia Rheumatica and Rheumatic Arthritis Patients—Links to Triggers and Proteomic Manifestations

TL;DR

This study explores the blood protein patterns in patients with polymyalgia rheumatica before and after treatment, revealing key proteins linked to inflammation and treatment response.

Contribution

The study provides new insights into the serum proteome and inflammatory markers in glucocorticoid-treated polymyalgia rheumatica patients.

Findings

Serum amyloid A (SAA1) levels significantly decrease with glucocorticoid treatment in PMR patients.

Interleukin-6 (IL-6) and interferon-gamma (IFN-γ) are significantly affected by treatment.

PGLYRP2 may indicate a bacterial infection response in acute PMR.

Abstract

Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation.

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