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Rheumatoid Arthritis Morning Stiffness Is Associated With Synovial Fibrin and Neutrophils
Author(s) -
Orange Dana E.,
Blachere Nathalie E.,
DiCarlo Edward F.,
Mirza Serene,
Pannellini Tania,
Jiang Caroline S.,
Frank Mayu O.,
Parveen Salina,
Figgie Mark P.,
Gravallese Ellen M.,
Bykerk Vivian P.,
Orbai AnaMaria,
Mackie Sarah L.,
Goodman Susan M.
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41141
Subject(s) - fibrin , medicine , fibrinolysis , rheumatoid arthritis , synovial membrane , morning , arthritis , pathology , morning stiffness , synovitis , immunology , psoriatic arthritis
Objective Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. This study was undertaken to determine whether any histologic features of synovium are associated with this symptom. Methods Data on patient‐reported morning stiffness duration and severity, and Disease Activity Score in 28 joints (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Synovium was scored for 10 histopathologic features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells, detritus, neutrophils, and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays. Results Stiffness severity and morning stiffness duration were both significantly associated with DAS28 ( P = 0.0001 and P = 0.001, respectively). None of the synovial features examined were associated with patient‐reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly associated ( P < 0.0001) with patient‐reported morning stiffness of ≥1 hour, such that 73% of patients with both synovial fibrin and neutrophils reported morning stiffness of ≥1 hour. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells ( P = 0.008). DNase I treatment of necrotic neutrophils abrogated the delay in fibrinolysis. Conclusion In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil‐enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiologic phenomena.