Sex differences in circulating proteins of patients with rheumatoid arthritis: A cohort study

• Published in: International journal of rheumatic diseases 2022-06, Vol.25 (6), p.669-677
• Main Authors: Ferreira, Maria Betânia, Fonseca, Tomás, Costa, Rita, Marinho, António, Oliveira, José C., Zannad, Faiez, Rossignol, Patrick, Rodrigues, Patrícia, Barros, António S., Ferreira, João P.
• Format: Article
• Language: English
• Subjects: Adipose tissue; Angiogenesis; Biomarkers; Calcium-binding protein; Cardiology and cardiovascular system; Chronic obstructive pulmonary disease; Cohort analysis; Diabetes mellitus; Extracellular matrix; Gender differences; Human health and pathology; Inflammation; Leptin; Life Sciences; Lung diseases; Matrix metalloproteinase; Metalloproteinase; Obstructive lung disease; pathophysiology; Patients; Proteins; proteomic biomarkers; Proteomics; Rheumatoid arthritis; Sex differences; Troponin; Vascular endothelial growth factor; Women
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.14323

Objectives Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in rheumatoid arthritis (RA). Studies focusing on sex differences in circulating proteins in RA patients are scarce. Our objective was to investigate the sex differences in circulating proteins of RA patients. Methods Cohort study enrolling 399 RA patients. Ninety‐four circulating protein‐biomarkers (92CVDIIOlink® + troponin‐T + C‐reactive protein) were measured. Clinical, demographic, and echocardiographic characteristics were compared between men and women. Sex differences in biomarker expression were assessed using regression modeling. Results In all, 306 (76.7%) patients were women. Compared with men, women had less visceral fat, smoked less, had diabetes and chronic obstructive pulmonary disease less frequently, and expressed more fatigue, anxiety, and depression. The association with cardiovascular outcomes did not differ between sexes. After adjusting for potential confounders, women expressed higher levels of circulating proteins related to adipokine signaling and vascular function (eg, leptin and vascular endothelial growth factor), whereas men expressed higher levels of circulating proteins related to extracellular matrix organization and inflammation (eg, matrix metalloproteinase‐2 and C‐reactive protein). These results were not found in patients without RA. Conclusion Sex differences in circulating proteins reflect distinct pathways implicated in the pathogenesis of RA, including inflammation, adiposity, angiogenesis, and extracellular matrix organization. These findings may help further investigations into factors underlying sex‐based differences and allow future studies focused on sex‐specific personalized treatment approaches in RA. ClinicalTrials.gov ID: NCT03960515.