外周血滤泡辅助性T细胞与B细胞在酒精性股骨头坏死患者中的作用
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摘要
目的:探讨酒精相关性股骨头坏死患者外周血滤泡辅助性T细胞、B细胞、白细胞介素(IL)-21的表达水平与疾病临床相关指标的相关性及其在酒精性股骨头坏死发病机制中的作用。方法:流式细胞仪测定酒精性股骨头坏死患者和健康对照组外周血中Tfh和B细胞的水平;ELISA法检测患者和健康对照血清中IL-21的表达水平。结果:酒精性股骨头坏死患者外周血CD19+B细胞、CD86+CD19+B细胞、CD95+CD19+B细胞Tfh细胞、PD-1+Tfh细胞和IL-21+Tfh细胞百分率高于对照组;外周血Tfh细胞百分率与CD19+B细胞百分率呈正相关,外周血IL-21+Tfh细胞百分率与CD86+CD19+B细胞百分率呈正相关,CD27+CD19+B细胞较对照组明显减少,CD86+CD19+B细胞百分率与股骨头坏死评分呈正相关。结论:酒精性股骨头坏死患者外周血Tfh细胞及B细胞水平显著增高,CD86+B细胞与疾病进展具有相关性,且Tfh细胞与B细胞的变化在疾病中具有显著的相关性,提示Tfh-B细胞相互作用在酒精性股骨头坏死的发病过程中发挥着重要作用。
Objective: To examine the roles of follicular helper T( Tfh) cells,serum IL-21 and B cells in the pathogenesis of alcohol abuse non-traumatic osteonecrosis of the femoral head( NONFH). Flow cytometry was used to measure the frequencies of peripheral blood inducible Tfh cells and B cells in alcohol abuse NONFH patients and healthy controls. The disease progression and the extent of femoral head collapse,the serum IL-21 were quantified. Methods: A significantly higher percentages of CD19+B cells( t = 3. 765,P =0. 0005),CD86+CD19+B cells( t = 5. 506,P < 0. 0001),and CD95+CD19+B cells( t = 4. 152,P = 0. 0002) in patients than those in controls was found. The percentages of CD86+CD19+B cells were positively associated with the index of femoral head collapse in alcohol abuse NONFH( P < 0. 0001,r = 0. 536). Results: The frequencies of Tfh cells( t = 7. 611,P < 0. 0001),and IL-21+Tfh cells( t =5. 281,P < 0. 0001) were higher than those in controls; The frequencies of Tfh cells were positively associated with the percentages of CD19+B cells( P = 0. 0002,r = 0. 455),IL-21+Tfh cells were positively associated with the percentages of CD86+CD19+B cells( P =0. 0002,r = 0. 447). Conclusion: Tfh cells and B cells may participate in the pathogenesis of alcohol abuse NONFH,and increased CD86+CD19+B cells may be associated with the extent of femoral head collapse,the interaction of Tfh cells and B cells may have an important role in pathogenesis of alcohol abuse NONFH.
Objective: To examine the roles of follicular helper T( Tfh) cells,serum IL-21 and B cells in the pathogenesis of alcohol abuse non-traumatic osteonecrosis of the femoral head( NONFH). Flow cytometry was used to measure the frequencies of peripheral blood inducible Tfh cells and B cells in alcohol abuse NONFH patients and healthy controls. The disease progression and the extent of femoral head collapse,the serum IL-21 were quantified. Methods: A significantly higher percentages of CD19+B cells( t = 3. 765,P =0. 0005),CD86+CD19+B cells( t = 5. 506,P < 0. 0001),and CD95+CD19+B cells( t = 4. 152,P = 0. 0002) in patients than those in controls was found. The percentages of CD86+CD19+B cells were positively associated with the index of femoral head collapse in alcohol abuse NONFH( P < 0. 0001,r = 0. 536). Results: The frequencies of Tfh cells( t = 7. 611,P < 0. 0001),and IL-21+Tfh cells( t =5. 281,P < 0. 0001) were higher than those in controls; The frequencies of Tfh cells were positively associated with the percentages of CD19+B cells( P = 0. 0002,r = 0. 455),IL-21+Tfh cells were positively associated with the percentages of CD86+CD19+B cells( P =0. 0002,r = 0. 447). Conclusion: Tfh cells and B cells may participate in the pathogenesis of alcohol abuse NONFH,and increased CD86+CD19+B cells may be associated with the extent of femoral head collapse,the interaction of Tfh cells and B cells may have an important role in pathogenesis of alcohol abuse NONFH.
引文
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[14]Linterman MA,Liston A,Vinuesa CG.T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells[J].Immunol Rev,2012,247(1):143-159.
[15]雷玲彦,郭惠芳,张明峰,等.Tfh细胞在原发性干燥综合征中的致病作用[J].中国免疫学杂志,2014,30(3):392-396.
[16]Kwok SK,Cho ml,Park MK,et al.Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis[J].Arthritis Rheum,2012,64(3):740-751.
[17]Wang J,Shan Y,Jiang Z,et al.High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis[J].Clin Exp Immunol,2013,174(2):212-220.
[18]Kotake S,Udagawa N,Hakoda M,et al.Activated human T cells directly induce osteoclastogenesis from human monocytes:possible role of T cells in bone destruction in rheumatoid arthritis patients[J].Arthritis Rheum,2001,44(5):1003-1012.
[19]张立智,蒋垚.骨的免疫学研究进展[J].中国际骨科学杂志,2009,30(4):218-221.
[2]Zalavras CG,Lieberman JR.Osteonecrosis of the femoral head:evaluation and treatment[J].J Am Acad Orthop Surg,2014,22(7):455-64.
[3]Lykissas MG,Gelalis ID,Kostas-Agnantis IP,et al.The role of hypercoagulability in the development of osteonecrosis of the femoral head[J].Orthop Rev(Pavia),2012,4(2):e17.
[4]Qi H,Chen X,Chu C,et al.Tfh cell differentiation and their function in promoting B-cell responses[J].Adv Exp Med Biol,2014,841:153-80.
[5]Mont MA,Jones LC,Hungerford DS.Nontraumatic osteonecrosis of the femoral head:ten years later[J].J Bone Joint Surg Am,2006,88:1117.
[6]Ficat RP.Idiopathic bone necrosis of the femoral head.Early diagnosis and treatment[J].J Bone Joint Surg Br,1985:67:3.
[7]Deng JC,Wang Y,Lv B,et al.Evaluation Guidelines for femoral head collapse severity[J].J Chin J Clinicians,2012,6:1570.
[8]Kim HS,Bae SC,Kim TH,et al.Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus[J].Int Orthop,2013,37(11):2289-2296.
[9]Van Vugt RM,Sijbrandij ES,Bijlsma JW.Magnetic resonance imaging of the femoral head to detect avascularnecrosis in active rheumatoid arthritis treated with methylprednisolone pulse therapy[J].JRheumatol,1996,25:74.
[10]Okazaki S,Nishitani Y,Nagoya S,et al.Femoral head osteonecrosis can be caused by disruption of the systemic immune response via the toll-like receptor 4 signalling pathway[J].Rheumatology,2009,48:227.
[11]Agematsu K.Memory B-cells and CD27[J].Histol Histopathol,2000,15:573-576.
[12]Godowski PJ.A smooth operator for LPS responses[J].Nat Immunol,2005,6:544.
[13]Dang LV,Nilsson A,Ingelman-Sundberg H,et al.Soluble CD27induces Ig G production through activation of antigen-primed B cells[J].J Intern Med,2012,271(3):282-293.
[14]Linterman MA,Liston A,Vinuesa CG.T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells[J].Immunol Rev,2012,247(1):143-159.
[15]雷玲彦,郭惠芳,张明峰,等.Tfh细胞在原发性干燥综合征中的致病作用[J].中国免疫学杂志,2014,30(3):392-396.
[16]Kwok SK,Cho ml,Park MK,et al.Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis[J].Arthritis Rheum,2012,64(3):740-751.
[17]Wang J,Shan Y,Jiang Z,et al.High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis[J].Clin Exp Immunol,2013,174(2):212-220.
[18]Kotake S,Udagawa N,Hakoda M,et al.Activated human T cells directly induce osteoclastogenesis from human monocytes:possible role of T cells in bone destruction in rheumatoid arthritis patients[J].Arthritis Rheum,2001,44(5):1003-1012.
[19]张立智,蒋垚.骨的免疫学研究进展[J].中国际骨科学杂志,2009,30(4):218-221.