Inge R Klein-Wieringa1, Badelog J E de Lange-Brokaar1, Erlangga Yusuf1, Stefan N Andersen1, Joanneke C Kwekkeboom1, Herman M Kroon1, Gerjo J V M van Osch1, Anne-Marie Zuurmond1, Vedrana Stojanovic-Susulic1, Rob G H H Nelissen1, René E M Toes1, Margreet Kloppenburg1, Andreea Ioan-Facsinay2. 1. From the Department of Rheumatology, Leiden University Medical Centre; Department of Radiology, Department of Orthopedics, and Department of Clinical Epidemiology, Leiden University Medical Center; TNO, Leiden; Department of Orthopedics and Otorhinolaryngology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; The Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, Pennsylvania, USA.I.R. Klein-Wieringa*, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; B.J. de Lange-Brokaar*, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; E. Yusuf, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; S.N. Andersen, Ing, Department of Rheumatology, Leiden University Medical Centre; J.C. Kwekkeboom, Ing, Department of Rheumatology, Leiden University Medical Centre; H.M. Kroon, PhD, Department of Radiology, Leiden University Medical Center; G.J. van Osch, PhD, Professor, Department of Orthopedics and Otorhinolaryngology, Erasmus MC, University Medical Center; A.M. Zuurmond, PhD, TNO; V. Stojanovic-Susulic, PhD, Janssen Pharmaceutical Companies of Johnson & Johnson; R.G. Nelissen, MD, PhD, Professor, Department of Orthopedics, Leiden University Medical Center; R.E. Toes, PhD, Professor, Department of Rheumatology, Leiden University Medical Centre; M. Kloppenburg, MD, PhD, Professor, Department of Rheumatology, and Department of Clinical Epidemiology, Leiden University Medical Centre; A. Ioan-Facsinay, PhD, Assistant Professor, Department of Rheumatology, Leiden University Medical Centre. 2. From the Department of Rheumatology, Leiden University Medical Centre; Department of Radiology, Department of Orthopedics, and Department of Clinical Epidemiology, Leiden University Medical Center; TNO, Leiden; Department of Orthopedics and Otorhinolaryngology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; The Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, Pennsylvania, USA.I.R. Klein-Wieringa*, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; B.J. de Lange-Brokaar*, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; E. Yusuf, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; S.N. Andersen, Ing, Department of Rheumatology, Leiden University Medical Centre; J.C. Kwekkeboom, Ing, Department of Rheumatology, Leiden University Medical Centre; H.M. Kroon, PhD, Department of Radiology, Leiden University Medical Center; G.J. van Osch, PhD, Professor, Department of Orthopedics and Otorhinolaryngology, Erasmus MC, University Medical Center; A.M. Zuurmond, PhD, TNO; V. Stojanovic-Susulic, PhD, Janssen Pharmaceutical Companies of Johnson & Johnson; R.G. Nelissen, MD, PhD, Professor, Department of Orthopedics, Leiden University Medical Center; R.E. Toes, PhD, Professor, Department of Rheumatology, Leiden University Medical Centre; M. Kloppenburg, MD, PhD, Professor, Department of Rheumatology, and Department of Clinical Epidemiology, Leiden University Medical Centre; A. Ioan-Facsinay, PhD, Assistant Professor, Department of Rheumatology, Leiden University Medical Centre. a.ioan@lumc.nl.
Abstract
OBJECTIVE: To get a better understanding of inflammatory pathways active in the osteoarthritic (OA) joint, we characterized and compared inflammatory cells in the synovium and the infrapatellar fat pad (IFP) of patients with knee OA. METHODS: Infiltrating immune cells were characterized by flow cytometry in 76 patients with knee OA (mean age 63.3, 52% women, median body mass index 28.9) from whom synovial tissue (n = 40) and IFP (n = 68) samples were obtained. Pain was assessed by the visual analog scale (VAS; 0-100 mm). Spearman rank correlations and linear regression analyses adjusted for sex and age were performed. RESULTS: Macrophages and T cells, followed by mast cells, were the most predominant immune cells in the synovium and IFP, and were equally abundant in these tissues. Macrophages and T cells secreted mostly proinflammatory cytokines even without additional stimulation, indicating their activated state. Accordingly, most CD4+ T cells had a memory phenotype and contained a significant population of cells expressing activation markers (CD25+, CD69+). Interestingly, the percent of CD69+ T cells was higher in synovial than IFP CD4+ T cells. Preliminary analyses indicated that the number of synovial CD4+ T cells were associated with VAS pain (β 0.51, 95% CI 0.09-1.02, p = 0.02). CONCLUSION: Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee.
OBJECTIVE: To get a better understanding of inflammatory pathways active in the osteoarthritic (OA) joint, we characterized and compared inflammatory cells in the synovium and the infrapatellar fat pad (IFP) of patients with knee OA. METHODS: Infiltrating immune cells were characterized by flow cytometry in 76 patients with knee OA (mean age 63.3, 52% women, median body mass index 28.9) from whom synovial tissue (n = 40) and IFP (n = 68) samples were obtained. Pain was assessed by the visual analog scale (VAS; 0-100 mm). Spearman rank correlations and linear regression analyses adjusted for sex and age were performed. RESULTS: Macrophages and T cells, followed by mast cells, were the most predominant immune cells in the synovium and IFP, and were equally abundant in these tissues. Macrophages and T cells secreted mostly proinflammatory cytokines even without additional stimulation, indicating their activated state. Accordingly, most CD4+ T cells had a memory phenotype and contained a significant population of cells expressing activation markers (CD25+, CD69+). Interestingly, the percent of CD69+ T cells was higher in synovial than IFP CD4+ T cells. Preliminary analyses indicated that the number of synovial CD4+ T cells were associated with VAS pain (β 0.51, 95% CI 0.09-1.02, p = 0.02). CONCLUSION: Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee.