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Published in: Clinical Rheumatology 8/2014

01-08-2014 | Original Article

Role of cytolytic impairment of natural killer and natural killer T-cell populations in rheumatoid arthritis

Authors: Ashish Aggarwal, Aman Sharma, Archana Bhatnagar

Published in: Clinical Rheumatology | Issue 8/2014

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Abstract

Innate immunity has been widely accepted as one of the major cause for the alteration of immune system and progression of autoimmune diseases. Natural killer (NK) cells and natural killer T (NKT) cells have not been explored in clinical studies for their cytolytic components in association with rheumatoid arthritis (RA). The literature available for these potential candidates is controversial in terms of their protective or pathogenic role in disease severity of RA. Present study explained the role of NK and NKT cell populations and intracellular expression of caspases, perforin, granzymes A and B in the pathogenesis of RA in patients. DAS28 score was measured as the disease severity. Immunochemical parameters were studied by using monoclonal antibodies (mAbs) against different cell types in flow cytometry. Results indicated that that whatsoever is the change in percentage cell populations, ratio of NK and NKT cell populations always remained poised even in the disease state. Reactive oxygen species (ROS) levels were elevated with increased intracellular active caspase-3, perforin and granzyme expression in RA patients. Their elevated expressions were positively correlated with DAS28 suggesting the pathogenic role in RA. The expressions of pro-inflammatory cytokines were enhanced while the anti-inflammatory cytokine expressions were diminished in the patients. Present study may point towards futuristic therapeutic targets which can fascinate the pharmaceutical industries to selectively target these molecules in designing the therapeutic strategy of RA patients.
Literature
1.
go back to reference Maini RN (1998) Rheumatoid arthritis. A paradigm of inflammatory disease of the musculoskeletal system. Acta Orthop Scand Suppl 281:6–13PubMed Maini RN (1998) Rheumatoid arthritis. A paradigm of inflammatory disease of the musculoskeletal system. Acta Orthop Scand Suppl 281:6–13PubMed
4.
go back to reference Flodstrom M, Shi FD, Sarvetnick N, Ljunggren HG (2002) The natural killer cell — friend or foe in autoimmune disease? Scand J Immunol 55(5):432–441PubMedCrossRef Flodstrom M, Shi FD, Sarvetnick N, Ljunggren HG (2002) The natural killer cell — friend or foe in autoimmune disease? Scand J Immunol 55(5):432–441PubMedCrossRef
5.
6.
go back to reference Heibein JA, Goping IS, Barry M, Pinkoski MJ, Shore GC, Green DR, Bleackley RC (2000) Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members bid and Bax. J Exp Med 192(10):1391–1402PubMedCentralPubMedCrossRef Heibein JA, Goping IS, Barry M, Pinkoski MJ, Shore GC, Green DR, Bleackley RC (2000) Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members bid and Bax. J Exp Med 192(10):1391–1402PubMedCentralPubMedCrossRef
7.
go back to reference Ronday HK, van der Laan WH, Tak PP, de Roos JA, Bank RA, TeKoppele JM, Froelich CJ, Hack CE, Hogendoorn PC, Breedveld FC, Verheijen JH (2001) Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis. Rheumatology (Oxford) 40(1):55–61CrossRef Ronday HK, van der Laan WH, Tak PP, de Roos JA, Bank RA, TeKoppele JM, Froelich CJ, Hack CE, Hogendoorn PC, Breedveld FC, Verheijen JH (2001) Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis. Rheumatology (Oxford) 40(1):55–61CrossRef
10.
go back to reference Froelich CJ, Zhang X, Turbov J, Hudig D, Winkler U, Hanna WL (1993) Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by chondrocytes. J Immunol 151(12):7161–7171PubMed Froelich CJ, Zhang X, Turbov J, Hudig D, Winkler U, Hanna WL (1993) Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by chondrocytes. J Immunol 151(12):7161–7171PubMed
12.
go back to reference Sower LE, Klimpel GR, Hanna W, Froelich CJ (1996) Extracellular Activities of Human Granzymes. Cell Immunol 171(1):159–163CrossRef Sower LE, Klimpel GR, Hanna W, Froelich CJ (1996) Extracellular Activities of Human Granzymes. Cell Immunol 171(1):159–163CrossRef
13.
go back to reference de Jager W, Vastert SJ, Beekman JM, Wulffraat NM, Kuis W, Coffer PJ, Prakken BJ (2009) Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 60(9):2782–2793. doi:10.1002/art.24750 PubMedCrossRef de Jager W, Vastert SJ, Beekman JM, Wulffraat NM, Kuis W, Coffer PJ, Prakken BJ (2009) Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 60(9):2782–2793. doi:10.​1002/​art.​24750 PubMedCrossRef
16.
go back to reference Lo CK, Lam QL, Sun L, Wang S, Ko KH, Xu H, Wu CY, Zheng BJ, Lu L (2008) Natural killer cell degeneration exacerbates experimental arthritis in mice via enhanced interleukin-17 production. Arthritis Rheum 58(9):2700–2711. doi:10.1002/art.23760 PubMedCrossRef Lo CK, Lam QL, Sun L, Wang S, Ko KH, Xu H, Wu CY, Zheng BJ, Lu L (2008) Natural killer cell degeneration exacerbates experimental arthritis in mice via enhanced interleukin-17 production. Arthritis Rheum 58(9):2700–2711. doi:10.​1002/​art.​23760 PubMedCrossRef
17.
18.
go back to reference Aramaki T, Ida H, Izumi Y, Fujikawa K, Huang M, Arima K, Tamai M, Kamachi M, Nakamura H, Kawakami A, Origuchi T, Matsuoka N, Eguchi K (2009) A significantly impaired natural killer cell activity due to a low activity on a per-cell basis in rheumatoid arthritis. Mod Rheumatol 19(3):245–252. doi:10.1007/s10165-009-0160-6 PubMedCrossRef Aramaki T, Ida H, Izumi Y, Fujikawa K, Huang M, Arima K, Tamai M, Kamachi M, Nakamura H, Kawakami A, Origuchi T, Matsuoka N, Eguchi K (2009) A significantly impaired natural killer cell activity due to a low activity on a per-cell basis in rheumatoid arthritis. Mod Rheumatol 19(3):245–252. doi:10.​1007/​s10165-009-0160-6 PubMedCrossRef
20.
go back to reference Park YW, Kee SJ, Cho YN, Lee EH, Lee HY, Kim EM, Shin MH, Park JJ, Kim TJ, Lee SS, Yoo DH, Kang HS (2009) Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Arthritis Rheum 60(6):1753–1763. doi:10.1002/art.24556 PubMedCrossRef Park YW, Kee SJ, Cho YN, Lee EH, Lee HY, Kim EM, Shin MH, Park JJ, Kim TJ, Lee SS, Yoo DH, Kang HS (2009) Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Arthritis Rheum 60(6):1753–1763. doi:10.​1002/​art.​24556 PubMedCrossRef
22.
go back to reference Godfrey DI, Kinder SJ, Silvera P, Baxter AG (1997) Flow cytometric study of T cell development in NOD mice reveals a deficiency in alphabetaTCR+CDR−CD8− thymocytes. J Autoimmun 10(3):279–285PubMedCrossRef Godfrey DI, Kinder SJ, Silvera P, Baxter AG (1997) Flow cytometric study of T cell development in NOD mice reveals a deficiency in alphabetaTCR+CDR−CD8− thymocytes. J Autoimmun 10(3):279–285PubMedCrossRef
27.
go back to reference Shah D, Aggarwal A, Bhatnagar A, Kiran R, Wanchu A (2011) Association between T lymphocyte sub-sets apoptosis and peripheral blood mononuclear cells oxidative stress in systemic lupus erythematosus. Free Radic Res 45(5):559–567. doi:10.3109/10715762.2011.555765 PubMedCrossRef Shah D, Aggarwal A, Bhatnagar A, Kiran R, Wanchu A (2011) Association between T lymphocyte sub-sets apoptosis and peripheral blood mononuclear cells oxidative stress in systemic lupus erythematosus. Free Radic Res 45(5):559–567. doi:10.​3109/​10715762.​2011.​555765 PubMedCrossRef
30.
go back to reference Mellqvist UH, Hansson M, Brune M, Dahlgren C, Hermodsson S, Hellstrand K (2000) Natural killer cell dysfunction and apoptosis induced by chronic myelogenous leukemia cells: role of reactive oxygen species and regulation by histamine. Blood 96(5):1961–1968PubMed Mellqvist UH, Hansson M, Brune M, Dahlgren C, Hermodsson S, Hellstrand K (2000) Natural killer cell dysfunction and apoptosis induced by chronic myelogenous leukemia cells: role of reactive oxygen species and regulation by histamine. Blood 96(5):1961–1968PubMed
31.
go back to reference Winyard PG, Ryan B, Eggleton P, Nissim A, Taylor E, Lo Faro ML, Burkholz T, Szabo-Taylor KE, Fox B, Viner N, Haigh RC, Benjamin N, Jones AM, Whiteman M (2011) Measurement and meaning of markers of reactive species of oxygen, nitrogen and sulfur in healthy human subjects and patients with inflammatory joint disease. Biochem Soc Trans 39(5):1226–1232. doi:10.1042/BST0391226 PubMedCrossRef Winyard PG, Ryan B, Eggleton P, Nissim A, Taylor E, Lo Faro ML, Burkholz T, Szabo-Taylor KE, Fox B, Viner N, Haigh RC, Benjamin N, Jones AM, Whiteman M (2011) Measurement and meaning of markers of reactive species of oxygen, nitrogen and sulfur in healthy human subjects and patients with inflammatory joint disease. Biochem Soc Trans 39(5):1226–1232. doi:10.​1042/​BST0391226 PubMedCrossRef
36.
go back to reference Tarazona R, DelaRosa O, Peralbo E, Casado JG, Pena J, Solana R (2003) Human NKT cells in health and disease. Immunologia 22(4):359–370 Tarazona R, DelaRosa O, Peralbo E, Casado JG, Pena J, Solana R (2003) Human NKT cells in health and disease. Immunologia 22(4):359–370
37.
go back to reference Vastert SJ, van Wijk R, D'Urbano LE, de Vooght KM, de Jager W, Ravelli A, Magni-Manzoni S, Insalaco A, Cortis E, van Solinge WW, Prakken BJ, Wulffraat NM, de Benedetti F, Kuis W (2010) Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford) 49(3):441–449. doi:10.1093/rheumatology/kep418 CrossRef Vastert SJ, van Wijk R, D'Urbano LE, de Vooght KM, de Jager W, Ravelli A, Magni-Manzoni S, Insalaco A, Cortis E, van Solinge WW, Prakken BJ, Wulffraat NM, de Benedetti F, Kuis W (2010) Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford) 49(3):441–449. doi:10.​1093/​rheumatology/​kep418 CrossRef
38.
go back to reference Cho BA, Sim JH, Park JA, Kim HW, Yoo WH, Lee SH, Lee DS, Kang JS, Hwang YI, Lee WJ, Kang I, Lee EB, Kim HR (2012) Characterization of effector memory CD8+ T cells in the synovial fluid of rheumatoid arthritis. J Clin Immunol 32(4):709–720. doi:10.1007/s10875-012-9674-3 PubMedCrossRef Cho BA, Sim JH, Park JA, Kim HW, Yoo WH, Lee SH, Lee DS, Kang JS, Hwang YI, Lee WJ, Kang I, Lee EB, Kim HR (2012) Characterization of effector memory CD8+ T cells in the synovial fluid of rheumatoid arthritis. J Clin Immunol 32(4):709–720. doi:10.​1007/​s10875-012-9674-3 PubMedCrossRef
39.
go back to reference Stabler T, Piette JC, Chevalier X, Marini-Portugal A, Kraus VB (2004) Serum cytokine profiles in relapsing polychondritis suggest monocyte/macrophage activation. Arthritis Rheum 50(11):3663–3667. doi:10.1002/art.20613 PubMedCrossRef Stabler T, Piette JC, Chevalier X, Marini-Portugal A, Kraus VB (2004) Serum cytokine profiles in relapsing polychondritis suggest monocyte/macrophage activation. Arthritis Rheum 50(11):3663–3667. doi:10.​1002/​art.​20613 PubMedCrossRef
41.
go back to reference Lin NY, Beyer C, Giessl A, Kireva T, Scholtysek C, Uderhardt S, Munoz LE, Dees C, Distler A, Wirtz S, Kronke G, Spencer B, Distler O, Schett G, Distler JH (2013) Autophagy regulates TNFalpha-mediated joint destruction in experimental arthritis. Ann Rheum Dis 72(5):761–768. doi:10.1136/annrheumdis-2012-201671 PubMedCrossRef Lin NY, Beyer C, Giessl A, Kireva T, Scholtysek C, Uderhardt S, Munoz LE, Dees C, Distler A, Wirtz S, Kronke G, Spencer B, Distler O, Schett G, Distler JH (2013) Autophagy regulates TNFalpha-mediated joint destruction in experimental arthritis. Ann Rheum Dis 72(5):761–768. doi:10.​1136/​annrheumdis-2012-201671 PubMedCrossRef
42.
go back to reference Haugeberg G, Conaghan PG, Quinn M, Emery P (2009) Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study. Ann Rheum Dis 68(12):1898–1901. doi:10.1136/ard.2008.106484 PubMedCrossRef Haugeberg G, Conaghan PG, Quinn M, Emery P (2009) Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study. Ann Rheum Dis 68(12):1898–1901. doi:10.​1136/​ard.​2008.​106484 PubMedCrossRef
43.
go back to reference Zhang W, Cong XL, Qin YH, He ZW, He DY, Dai SM (2013) IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis. Inflammation 36(1):103–109. doi:10.1007/s10753-012-9524-8 PubMedCrossRef Zhang W, Cong XL, Qin YH, He ZW, He DY, Dai SM (2013) IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis. Inflammation 36(1):103–109. doi:10.​1007/​s10753-012-9524-8 PubMedCrossRef
44.
go back to reference Karonitsch T, von Dalwigk K, Steiner CW, Bluml S, Steiner G, Kiener HP, Smolen JS, Aringer M (2012) Interferon signals and monocytic sensitization of the interferon-gamma signaling pathway in the peripheral blood of patients with rheumatoid arthritis. Arthritis Rheum 64(2):400–408. doi:10.1002/art.33347 PubMedCrossRef Karonitsch T, von Dalwigk K, Steiner CW, Bluml S, Steiner G, Kiener HP, Smolen JS, Aringer M (2012) Interferon signals and monocytic sensitization of the interferon-gamma signaling pathway in the peripheral blood of patients with rheumatoid arthritis. Arthritis Rheum 64(2):400–408. doi:10.​1002/​art.​33347 PubMedCrossRef
45.
go back to reference van Baarsen LG, Bos WH, Rustenburg F, van der Pouw Kraan TC, Wolbink GJ, Dijkmans BA, van Schaardenburg D, Verweij CL (2010) Gene expression profiling in autoantibody-positive patients with arthralgia predicts development of arthritis. Arthritis Rheum 62(3):694–704. doi:10.1002/art.27294 PubMedCrossRef van Baarsen LG, Bos WH, Rustenburg F, van der Pouw Kraan TC, Wolbink GJ, Dijkmans BA, van Schaardenburg D, Verweij CL (2010) Gene expression profiling in autoantibody-positive patients with arthralgia predicts development of arthritis. Arthritis Rheum 62(3):694–704. doi:10.​1002/​art.​27294 PubMedCrossRef
46.
go back to reference Cantaert T, van Baarsen LG, Wijbrandts CA, Thurlings RM, van de Sande MG, Bos C, van der Pouw TK, Verweij CL, Tak PP, Baeten DL (2010) Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis. Rheumatology (Oxford) 49(1):156–166. doi:10.1093/rheumatology/kep345 CrossRef Cantaert T, van Baarsen LG, Wijbrandts CA, Thurlings RM, van de Sande MG, Bos C, van der Pouw TK, Verweij CL, Tak PP, Baeten DL (2010) Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis. Rheumatology (Oxford) 49(1):156–166. doi:10.​1093/​rheumatology/​kep345 CrossRef
47.
go back to reference Endo H, Akahoshi T, Takagishi K, Kashiwazaki S, Matsushima K (1991) Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthritis and the induction by IL-8 of leukocyte infiltration and synovitis in rabbit joints. Lymphokine Cytokine Res 10(4):245–252PubMed Endo H, Akahoshi T, Takagishi K, Kashiwazaki S, Matsushima K (1991) Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthritis and the induction by IL-8 of leukocyte infiltration and synovitis in rabbit joints. Lymphokine Cytokine Res 10(4):245–252PubMed
48.
go back to reference Chen DY, Hsieh TY, Chen YM, Hsieh CW, Lan JL, Lin FJ (2009) Proinflammatory cytokine profiles of patients with elderly-onset rheumatoid arthritis: a comparison with younger-onset disease. Gerontology 55(3):250–258. doi:10.1159/000164393 PubMedCrossRef Chen DY, Hsieh TY, Chen YM, Hsieh CW, Lan JL, Lin FJ (2009) Proinflammatory cytokine profiles of patients with elderly-onset rheumatoid arthritis: a comparison with younger-onset disease. Gerontology 55(3):250–258. doi:10.​1159/​000164393 PubMedCrossRef
50.
go back to reference Balsa A, Del Amo J, Blanco F, Caliz R, Silva L, Sanmarti R, Martinez FG, Tejedor D, Artieda M, Pascual-Salcedo D, Oreiro N, Collado MD, Andreu JL, Graell E, Simon L, Martinez A, Mulero J (2010) Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms. Rheumatology (Oxford) 49(3):458–466. doi:10.1093/rheumatology/kep380 CrossRef Balsa A, Del Amo J, Blanco F, Caliz R, Silva L, Sanmarti R, Martinez FG, Tejedor D, Artieda M, Pascual-Salcedo D, Oreiro N, Collado MD, Andreu JL, Graell E, Simon L, Martinez A, Mulero J (2010) Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms. Rheumatology (Oxford) 49(3):458–466. doi:10.​1093/​rheumatology/​kep380 CrossRef
51.
go back to reference Sarkar S, Cooney LA, White P, Dunlop DB, Endres J, Jorns JM, Wasco MJ, Fox DA (2009) Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4. Arthritis Res Ther 11(5):R158. doi:10.1186/ar2838 PubMedCentralPubMedCrossRef Sarkar S, Cooney LA, White P, Dunlop DB, Endres J, Jorns JM, Wasco MJ, Fox DA (2009) Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4. Arthritis Res Ther 11(5):R158. doi:10.​1186/​ar2838 PubMedCentralPubMedCrossRef
53.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69(9):1580–1588. doi:10.1136/ard.2010.138461 PubMedCrossRef Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69(9):1580–1588. doi:10.​1136/​ard.​2010.​138461 PubMedCrossRef
54.
go back to reference Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48PubMedCrossRef Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48PubMedCrossRef
55.
go back to reference Kay HD (1980) A new procedure to overlay diluted blood on Ficoll-hypaque gradients. J Immunol Methods 39(1–2):81–83PubMed Kay HD (1980) A new procedure to overlay diluted blood on Ficoll-hypaque gradients. J Immunol Methods 39(1–2):81–83PubMed
56.
go back to reference Lanier LL, Testi R, Bindl J, Phillips JH (1989) Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 169(6):2233–2238PubMedCrossRef Lanier LL, Testi R, Bindl J, Phillips JH (1989) Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 169(6):2233–2238PubMedCrossRef
57.
go back to reference Sarkar M, Varshney R, Chopra M, Sekhri T, Adhikari JS, Dwarakanath BS (2006) Flow-cytometric analysis of reactive oxygen species in peripheral blood mononuclear cells of patients with thyroid dysfunction. Cytometry B Clin Cytom 70(1):20–23. doi:10.1002/cyto.b.20082 PubMedCrossRef Sarkar M, Varshney R, Chopra M, Sekhri T, Adhikari JS, Dwarakanath BS (2006) Flow-cytometric analysis of reactive oxygen species in peripheral blood mononuclear cells of patients with thyroid dysfunction. Cytometry B Clin Cytom 70(1):20–23. doi:10.​1002/​cyto.​b.​20082 PubMedCrossRef
Metadata
Title
Role of cytolytic impairment of natural killer and natural killer T-cell populations in rheumatoid arthritis
Authors
Ashish Aggarwal
Aman Sharma
Archana Bhatnagar
Publication date
01-08-2014
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 8/2014
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-014-2641-z

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