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Synovial Immunophenotype and Anti–Citrullinated Peptide Antibodies in Rheumatoid Arthritis Patients
Author(s) -
Orr Carl,
Najm Aurelie,
Biniecka Monika,
McGarry Trudy,
Ng ChinTeck,
Young Francis,
Fearon Ursula,
Veale Douglas J.
Publication year - 2017
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.40218
Subject(s) - medicine , rheumatoid arthritis , rheumatism , immunophenotyping , antibody , rheumatology , rheumatoid factor , serology , arthritis , immunology , synovial membrane , pathology , gastroenterology , antigen
Objective Serum anti–citrullinated peptide antibodies ( ACPA s) may be present before the development of rheumatoid arthritis ( RA ) and may be predictive of more severe, erosive disease. This study was undertaken to examine the synovial tissue immunophenotype according to ACPA status in patients with RA , as well as the response to treatment and erosion status. Methods Consecutive RA patients were prospectively recruited and underwent clinical and serologic assessments before and after treatment. Radiologic assessment was performed at the time of clinical follow‐up. Synovial tissue was immunostained for specific markers of B cells ( CD 19), T cells ( CD 3, CD 4, and CD 8), macrophages ( CD 68), and blood vessels (factor VIII ). Serum CXCL 13 levels were quantified by enzyme‐linked immunosorbent assay. Synovial tissue sections were analyzed for immunophenotype according to ACPA status, using a validated semiquantitative scoring method, and also analyzed for the presence of lymphoid aggregates. Response to treatment with nonbiologic or biologic disease‐modifying antirheumatic drugs was assessed using the European League Against Rheumatism ( EULAR ) response criteria. Results In total, 123 subjects (78 ACPA +) were included. Compared to ACPA – RA patients, synovium from ACPA + RA patients was characterized by significantly higher levels of CD 19+ B cells and CD 3+ and CD 8+ T cells (each P < 0.05), and CD 19+ B cell levels were significantly higher in patients who were naive to treatment. The CD 19+ B cell infiltrate level was higher in patients with erosions at follow‐up ( P = 0.0128). Levels of lymphoid aggregates of CD 19+ B cells were significantly higher in ACPA + patients ( P < 0.05), and this was associated with increased serum CXCL 13 levels. The EULAR response was significantly associated with the level of CD 3+ T cell infiltrates ( P < 0.05), while CD 68+ macrophage and CD 8+ T cell levels were predictive of the response to tumor necrosis factor inhibitors ( P < 0.05). Conclusion The results of this prospective study demonstrate that the levels of synovial B cell infiltrates and lymphoid aggregates were significantly higher in ACPA + RA patients, especially those who were naive to treatment. In addition, ACPA + subjects developed more erosions during progression of the disease and had higher serum levels of CXCL 13. The EULAR response to therapy in ACPA + RA patients was associated with increased levels of T cell and macrophage markers.