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Erschienen in: Clinical Rheumatology 2/2020

17.10.2019 | Original Article

Alterations in peripheral T cell and B cell subsets in patients with osteoarthritis

verfasst von: Wanshou Zhu, Xi Zhang, Yutong Jiang, Xiaolian Liu, Linyan Huang, QiuJing Wei, Yefei Huang, Weilong Wu, Jieruo Gu

Erschienen in: Clinical Rheumatology | Ausgabe 2/2020

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Abstract

Objectives

Our study objective was to explore whether abnormalities in the subtypes of T cells and B cells were present in peripheral blood of patients with osteoarthritis (OA) and healthy controls (HCs).

Method

Demographic and clinical variables and blood were collected. OA severity was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Flow cytometry was used to establish the frequencies of lineage subsets. Monoclonal antibodies against 21 surface markers were used to distinguish and evaluate T cells’ and B cells’ subpopulation. The proportion of each subset was compared and correlations between age, immune cells, and clinical data were analyzed.

Results

A total of 30 OA patients (male/female = 9/21) and 45 HCs (male/female = 14/31) were included. Median WOMAC pain was 3.0 (2.0). There was no difference in the proportion of T cells, CD8+ T cells, and B cells (p > 0.05). The proportion of CD4+ T cells was higher in OA groups, together with an increased CD4 to CD8 ratio (p = 0.016). CD8+CD45RA+ T cells were reduced after adjustment for age, while CD8+CD45RA− T cells were elevated in OA (p < 0.05). CD4+CD45RA−CCR7+ T cells and CD4+CD45RA−CCR7− T cells were increased (p < 0.004). The proportion of T helper (Th) 17 and T follicular helper (Tfh) 2 cells was higher, but cytotoxic T (Tc) 17 cells were fewer in OA (p < 0.05). CD3−CD19+IgD−IgM−CD27+CD38+ B cells were decreased in OA (p ≤ 0.001). The WOMAC pain score correlated with CD3+CD4+CXCR5−PD-1+ T cells positively (B = 0.404, p = 0.027). CD3−CD19+CD27−IgD+ cells correlated negatively with erythrocyte sedimentation rate (ESR) (B = −0.550, p = 0.005).

Conclusions

The T cell and B cell profiles were proved to have alteration suggesting that acquired immune system may play a substantial role in the pathogenesis of OA.
Key Points
• The T cell and B cell profiles were proved to have alteration suggesting that acquired immune system may play a substantial role in the pathogenesis of OA.
• The WOMAC pain score correlated with CD3+CD4+CXCR5−PD-1+ T cells and T helper 17 cells positively.
• Memory T cells were increased in OA patients, suggesting they could play an important role in OA.
Literatur
1.
Zurück zum Zitat Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L (2014) The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73:1323–1330CrossRef Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L (2014) The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73:1323–1330CrossRef
2.
Zurück zum Zitat Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF (2000) Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 133:635–646CrossRef Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF (2000) Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 133:635–646CrossRef
3.
Zurück zum Zitat Pawelec G (2012) Hallmarks of human “immunosenescence”: adaptation or dysregulation? Immun Ageing 9:15CrossRef Pawelec G (2012) Hallmarks of human “immunosenescence”: adaptation or dysregulation? Immun Ageing 9:15CrossRef
4.
Zurück zum Zitat Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21:16–21CrossRef Berenbaum F (2013) Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil 21:16–21CrossRef
5.
Zurück zum Zitat Huber-Lang M, Kovtun A, Ignatius A (2013) The role of complement in trauma and fracture healing. Semin Immunol 25:73–78CrossRef Huber-Lang M, Kovtun A, Ignatius A (2013) The role of complement in trauma and fracture healing. Semin Immunol 25:73–78CrossRef
6.
Zurück zum Zitat Geginat J, Paroni M, Facciotti F, Gruarin P, Kastirr I, Caprioli F, Pagani M, Abrignani S (2013) The CD4-centered universe of human T cell subsets. Semin Immunol 25:252–262CrossRef Geginat J, Paroni M, Facciotti F, Gruarin P, Kastirr I, Caprioli F, Pagani M, Abrignani S (2013) The CD4-centered universe of human T cell subsets. Semin Immunol 25:252–262CrossRef
7.
Zurück zum Zitat de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ et al (2012) Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthr Cartil 20:1484–1499CrossRef de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ et al (2012) Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthr Cartil 20:1484–1499CrossRef
8.
9.
Zurück zum Zitat Crotty S (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29:621–663CrossRef Crotty S (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29:621–663CrossRef
10.
Zurück zum Zitat Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh SK, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34:108–121CrossRef Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh SK, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34:108–121CrossRef
11.
Zurück zum Zitat Shan Y, Qi C, Liu Y, Gao H, Zhao D, Jiang Y (2017) Increased frequency of peripheral blood follicular helper T cells and elevated serum IL21 levels in patients with knee osteoarthritis. Mol Med Rep 15:1095–1102CrossRef Shan Y, Qi C, Liu Y, Gao H, Zhao D, Jiang Y (2017) Increased frequency of peripheral blood follicular helper T cells and elevated serum IL21 levels in patients with knee osteoarthritis. Mol Med Rep 15:1095–1102CrossRef
12.
Zurück zum Zitat Da RR, Qin Y, Baeten D, Zhang Y (2007) B cell clonal expansion and somatic hypermutation of Ig variable heavy chain genes in the synovial membrane of patients with osteoarthritis. J Immunol 178:557–565CrossRef Da RR, Qin Y, Baeten D, Zhang Y (2007) B cell clonal expansion and somatic hypermutation of Ig variable heavy chain genes in the synovial membrane of patients with osteoarthritis. J Immunol 178:557–565CrossRef
13.
Zurück zum Zitat Du H, Masuko-Hongo K, Nakamura H et al (2005) The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes. Rheumatol Int 26:35–41CrossRef Du H, Masuko-Hongo K, Nakamura H et al (2005) The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes. Rheumatol Int 26:35–41CrossRef
14.
Zurück zum Zitat Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T (2009) Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med 15:1072–1076CrossRef Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T (2009) Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat Med 15:1072–1076CrossRef
15.
Zurück zum Zitat Bellamy N, Buchanan WW, Goldsmith CH et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840PubMed Bellamy N, Buchanan WW, Goldsmith CH et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840PubMed
16.
Zurück zum Zitat Kondo T, Takata H, Takiguchi M (2007) Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells. Eur J Immunol 37:54–65CrossRef Kondo T, Takata H, Takiguchi M (2007) Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T cells. Eur J Immunol 37:54–65CrossRef
17.
Zurück zum Zitat Hermiston ML, Xu Z, Weiss A (2003) CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol 21:107–137CrossRef Hermiston ML, Xu Z, Weiss A (2003) CD45: a critical regulator of signaling thresholds in immune cells. Annu Rev Immunol 21:107–137CrossRef
18.
Zurück zum Zitat Appay V, Zaunders JJ, Papagno L, Sutton J, Jaramillo A, Waters A, Easterbrook P, Grey P, Smith D, McMichael AJ, Cooper DA, Rowland-Jones SL, Kelleher AD (2002) Characterization of CD4(+) CTLs ex vivo. J Immunol 168:5954–5958CrossRef Appay V, Zaunders JJ, Papagno L, Sutton J, Jaramillo A, Waters A, Easterbrook P, Grey P, Smith D, McMichael AJ, Cooper DA, Rowland-Jones SL, Kelleher AD (2002) Characterization of CD4(+) CTLs ex vivo. J Immunol 168:5954–5958CrossRef
19.
Zurück zum Zitat Haynes MK, Hume EL, Smith JB (2002) Phenotypic characterization of inflammatory cells from osteoarthritic synovium and synovial fluids. Clin Immunol 105:315–325CrossRef Haynes MK, Hume EL, Smith JB (2002) Phenotypic characterization of inflammatory cells from osteoarthritic synovium and synovial fluids. Clin Immunol 105:315–325CrossRef
20.
Zurück zum Zitat Ezawa K, Yamamura M, Matsui H, Ota Z, Makino H (1997) Comparative analysis of CD45RA- and CD45RO-positive CD4+T cells in peripheral blood, synovial fluid, and synovial tissue in patients with rheumatoid arthritis and osteoarthritis. Acta Med Okayama 51:25–31PubMed Ezawa K, Yamamura M, Matsui H, Ota Z, Makino H (1997) Comparative analysis of CD45RA- and CD45RO-positive CD4+T cells in peripheral blood, synovial fluid, and synovial tissue in patients with rheumatoid arthritis and osteoarthritis. Acta Med Okayama 51:25–31PubMed
21.
Zurück zum Zitat Ponchel F, Burska AN, Hensor EM et al (2015) Changes in peripheral blood immune cell composition in osteoarthritis. Osteoarthr Cartil 23:1870–1878CrossRef Ponchel F, Burska AN, Hensor EM et al (2015) Changes in peripheral blood immune cell composition in osteoarthritis. Osteoarthr Cartil 23:1870–1878CrossRef
22.
Zurück zum Zitat Sallusto F, Lenig D, Forster R et al (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708–712CrossRef Sallusto F, Lenig D, Forster R et al (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708–712CrossRef
23.
Zurück zum Zitat Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763CrossRef Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763CrossRef
24.
Zurück zum Zitat Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776CrossRef Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776CrossRef
25.
Zurück zum Zitat Zhang L, Li JM, Liu XG, Ma DX, Hu NW, Li YG, Li W, Hu Y, Yu S, Qu X, Yang MX, Feng AL, Wang GH (2011) Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J Clin Immunol 31:606–614CrossRef Zhang L, Li JM, Liu XG, Ma DX, Hu NW, Li YG, Li W, Hu Y, Yu S, Qu X, Yang MX, Feng AL, Wang GH (2011) Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J Clin Immunol 31:606–614CrossRef
26.
Zurück zum Zitat Qi C, Shan Y, Wang J, Ding F, Zhao D, Yang T, Jiang Y (2016) Circulating T helper 9 cells and increased serum interleukin-9 levels in patients with knee osteoarthritis. Clin Exp Pharmacol Physiol 43:528–534CrossRef Qi C, Shan Y, Wang J, Ding F, Zhao D, Yang T, Jiang Y (2016) Circulating T helper 9 cells and increased serum interleukin-9 levels in patients with knee osteoarthritis. Clin Exp Pharmacol Physiol 43:528–534CrossRef
27.
Zurück zum Zitat Kim J, Kang S, Kim J, Kwon G, Koo S (2013) Elevated levels of T helper 17 cells are associated with disease activity in patients with rheumatoid arthritis. Ann Lab Med 33:52–59CrossRef Kim J, Kang S, Kim J, Kwon G, Koo S (2013) Elevated levels of T helper 17 cells are associated with disease activity in patients with rheumatoid arthritis. Ann Lab Med 33:52–59CrossRef
28.
Zurück zum Zitat Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DAA, Ziegler SF (2013) Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol 14:307–308CrossRef Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DAA, Ziegler SF (2013) Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol 14:307–308CrossRef
29.
Zurück zum Zitat Wilkinson M, Rosser EC (2019) B cells as a therapeutic target in paediatric rheumatic disease. Front Immunol 10:214CrossRef Wilkinson M, Rosser EC (2019) B cells as a therapeutic target in paediatric rheumatic disease. Front Immunol 10:214CrossRef
30.
Zurück zum Zitat Shiokawa S, Matsumoto N, Nishimura J (2001) Clonal analysis of B cells in the osteoarthritis synovium. Ann Rheum Dis 60:802–805CrossRef Shiokawa S, Matsumoto N, Nishimura J (2001) Clonal analysis of B cells in the osteoarthritis synovium. Ann Rheum Dis 60:802–805CrossRef
Metadaten
Titel
Alterations in peripheral T cell and B cell subsets in patients with osteoarthritis
verfasst von
Wanshou Zhu
Xi Zhang
Yutong Jiang
Xiaolian Liu
Linyan Huang
QiuJing Wei
Yefei Huang
Weilong Wu
Jieruo Gu
Publikationsdatum
17.10.2019
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 2/2020
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-019-04768-y

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