腎臓移植後に産生されるHLA-DQ抗体と慢性抗体関連型拒絶反応の関係について
「I. はじめに」最新のHLA抗体検査技術や免疫抑制剤の進歩により, 急性拒絶反応の発症率の軽減, 短期の移植腎生着率は飛躍的に向上した. しかしながら, 移植腎喪失に陥ってしまった症例の主な廃絶原因は, 慢性抗体関連型拒絶反応(chronic antibody-mediated rejection : CAMR)と免疫抑制剤の怠薬が占める割合が多い傾向が現状である. 一般的にHLA抗体は, 移植や輸血, 妊娠などの自分以外の抗原に暴露された既往歴のある患者に多く認められ, HLA class I抗体陽性症例は女性, 出産, 輸血と関係が深いとされている. HLA class II抗体では,...
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| Published in | Japanese Journal of Transplantation Vol. 52; no. 1; pp. 051 - 059 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本移植学会
2017
日本移植学会 The Japan Society for Transplantation |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0578-7947 2188-0034 |
| DOI | 10.11386/jst.52.1_051 |
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| Abstract | 「I. はじめに」最新のHLA抗体検査技術や免疫抑制剤の進歩により, 急性拒絶反応の発症率の軽減, 短期の移植腎生着率は飛躍的に向上した. しかしながら, 移植腎喪失に陥ってしまった症例の主な廃絶原因は, 慢性抗体関連型拒絶反応(chronic antibody-mediated rejection : CAMR)と免疫抑制剤の怠薬が占める割合が多い傾向が現状である. 一般的にHLA抗体は, 移植や輸血, 妊娠などの自分以外の抗原に暴露された既往歴のある患者に多く認められ, HLA class I抗体陽性症例は女性, 出産, 輸血と関係が深いとされている. HLA class II抗体では, 移植腎機能の悪化と深い関係があるといわれ, HLA class I, II抗体の両方の抗体が陽性の症例では, 機能廃絶に陥る率が高いと報告されている. そして, 移植後に産生されるde novo抗体de novo donor-specific anti-HLA antibodies(dnDSA)は, CAMRと関係があり, 移植予後にも影響を与えるといわれている. |
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| AbstractList | 「I. はじめに」最新のHLA抗体検査技術や免疫抑制剤の進歩により, 急性拒絶反応の発症率の軽減, 短期の移植腎生着率は飛躍的に向上した. しかしながら, 移植腎喪失に陥ってしまった症例の主な廃絶原因は, 慢性抗体関連型拒絶反応(chronic antibody-mediated rejection : CAMR)と免疫抑制剤の怠薬が占める割合が多い傾向が現状である. 一般的にHLA抗体は, 移植や輸血, 妊娠などの自分以外の抗原に暴露された既往歴のある患者に多く認められ, HLA class I抗体陽性症例は女性, 出産, 輸血と関係が深いとされている. HLA class II抗体では, 移植腎機能の悪化と深い関係があるといわれ, HLA class I, II抗体の両方の抗体が陽性の症例では, 機能廃絶に陥る率が高いと報告されている. そして, 移植後に産生されるde novo抗体de novo donor-specific anti-HLA antibodies(dnDSA)は, CAMRと関係があり, 移植予後にも影響を与えるといわれている. 【Objective】Chronic antibody-mediated rejection (CAMR) is among the most important factors that affect the outcome of kidney allograft. de novo donor-specific anti-HLA antibodies (DSA) have been reported to be related to CAMR. However, it remains still unclear about the relationship between the characteristics of de novo DSA and CAMR.The aims of the present study were to (1) clarify the de novo incidence rate and (2) investigate the relationship between the characteristics of de novo DSA and CAMR in kidney transplant recipients 【Methods】One hundred and forty-five patients who had undergone kidney transplantation from 2000 to 2015 were screened for HLA antibodies. They were detected by using Luminex single antigen beads (One Lambda Inc.) with LABScan 100. 【Results】DSA after kidney transplantation were detected in 54 patients (37%), and de novo DSAs were demonstrated in 47 patients of these 54 (87%). In 47 patients with de novo DSA, 40 (85%) were found to have HLA-DQ DSA. Of these 40 patients, 32 (80%) were diagnosed with biopsy-proven acute AMR or CAMR 6 months or later posttransplant and 4 (12.5%) lost their kidney allografts. 【Conclusion】De novo HLA-DQ DSA were detected more frequently compared with HLA-class I or -DR DSA in kidney transplant recipients with CAMR. Screening for HLA-DQ DSA after kidney transplantation seems favorable to obtain better long-term outcomes of kidney allografts. |
| Author | 古澤, 美由紀 石田, 英樹 奥見, 雅由 清水, 朋一 田邉, 一成 |
| Author_FL | FURUSAWA Miyuki ISHIDA Hideki TANABE Kazunari OKUMI Masayoshi SHIMIZU Tomokazu |
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| References | 1) El-Zoghby ZM, Stegall MD, Lager DJ, et al. Identifying specific causes of kidney allograft loss. Am J Transplant 2009; 9: 527-535. 7) Cardarelli F, Pascual M, Tolkoff-Rubin N, et al. Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation. Transpl Int 2005; 18: 532-540. 17) Everly MJ, Everly JJ, Arend LJ, et al. Reducing de novo donor-specific antibody levels during acute rejection diminishes renal allograft loss. Am J Transplant 2009; 9: 1063-1071. 18) Lachman N, Terasaki PI, Budde K, et al. Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection or renal allografts. Transplantation 2009; 87: 1505-1513. 16) Willicombe M, Brookes P, Sergeant R, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation 2012; 94: 172-177. 3) Mahanty HD, Cherikh WS, Chanq GJ, et al. Influence of pretransplant pregnancy on survival of renal alloglaft from living donors. Transplantation 2001;72: 228-232. 19) Ginevri F, Nocera A, Comoli P, et al. Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody mediated rejection. Am J Transplant 2012; 12: 3355-3362. 13) Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12: 1157-1167. 10) Gloor JM, Sethi S, Stegall MD, et al. Transplant glomerulopathy: subclinical incidence and association with alloantibody. Am J Transplant 2007; 7: 2124-2132. 11) Issa N, Cosio FG, Gloor JM, et al. Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels. Transplantation 2008; 86: 681-685. 9) Pollinger HS, Stegall MD, Gloor JM, et al. Kidney transplantation in patients with antibodies against donor HLA class II. Am J Transplant 2007; 7: 857-863. 2) Marcén R. Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs 2009; 69: 2227-2243. 20) Ishida H, Furusawa M, Shimizu T, et al. Influence of preoperative anti-HLA antibodies on short- and long-term graft survival in recipients with or without rituximab treatment. Transpl Int 2014; 27: 371-382. 6) Hourmant M, Cesbron-Gautier A, Terasaki PI, et al. Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol 2005; 16: 2804-2812. 14) DeVos JM, Gaber AO, Knight RJ, et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int 2012; 82: 598-604. 15) Lim WH, Chapman JR, Coates PT, et al. HLA-DQ mismatches and rejection in kidney transplant recipients. Clin J Am Soc Nephrol 2016; 11: 875-883. 4) Campos EF, Tedesco-Silva H, Machado PG. Post-transplant anti-HLA ClassII antibodies as risk factor for late kidney a sllograft failure. Am J Transplant 2006; 6: 2316-2320 12) Willicombe M, Brookes P, Sergeant R, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody- mediated rejection and transplant glomerulopathy. Transplantation 2012; 94: 172-177. 5) Worthington JE, Martin S, Al-Husseini DM, et al. Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome. Transplantation 2003; 75: 1034-1040. 8) Hara S. Banff 2013 update: pearls and pitfalls in transplant renal pathology. Nephrology (Carlton) 2015; 20 (Suppl 2) : 2-8. |
| References_xml | – reference: 6) Hourmant M, Cesbron-Gautier A, Terasaki PI, et al. Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol 2005; 16: 2804-2812. – reference: 16) Willicombe M, Brookes P, Sergeant R, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation 2012; 94: 172-177. – reference: 7) Cardarelli F, Pascual M, Tolkoff-Rubin N, et al. Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation. Transpl Int 2005; 18: 532-540. – reference: 9) Pollinger HS, Stegall MD, Gloor JM, et al. Kidney transplantation in patients with antibodies against donor HLA class II. Am J Transplant 2007; 7: 857-863. – reference: 10) Gloor JM, Sethi S, Stegall MD, et al. Transplant glomerulopathy: subclinical incidence and association with alloantibody. Am J Transplant 2007; 7: 2124-2132. – reference: 18) Lachman N, Terasaki PI, Budde K, et al. Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection or renal allografts. Transplantation 2009; 87: 1505-1513. – reference: 1) El-Zoghby ZM, Stegall MD, Lager DJ, et al. Identifying specific causes of kidney allograft loss. Am J Transplant 2009; 9: 527-535. – reference: 15) Lim WH, Chapman JR, Coates PT, et al. HLA-DQ mismatches and rejection in kidney transplant recipients. Clin J Am Soc Nephrol 2016; 11: 875-883. – reference: 20) Ishida H, Furusawa M, Shimizu T, et al. Influence of preoperative anti-HLA antibodies on short- and long-term graft survival in recipients with or without rituximab treatment. Transpl Int 2014; 27: 371-382. – reference: 14) DeVos JM, Gaber AO, Knight RJ, et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int 2012; 82: 598-604. – reference: 4) Campos EF, Tedesco-Silva H, Machado PG. Post-transplant anti-HLA ClassII antibodies as risk factor for late kidney a sllograft failure. Am J Transplant 2006; 6: 2316-2320 – reference: 5) Worthington JE, Martin S, Al-Husseini DM, et al. Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome. Transplantation 2003; 75: 1034-1040. – reference: 11) Issa N, Cosio FG, Gloor JM, et al. Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels. Transplantation 2008; 86: 681-685. – reference: 8) Hara S. Banff 2013 update: pearls and pitfalls in transplant renal pathology. Nephrology (Carlton) 2015; 20 (Suppl 2) : 2-8. – reference: 2) Marcén R. Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs 2009; 69: 2227-2243. – reference: 3) Mahanty HD, Cherikh WS, Chanq GJ, et al. Influence of pretransplant pregnancy on survival of renal alloglaft from living donors. Transplantation 2001;72: 228-232. – reference: 12) Willicombe M, Brookes P, Sergeant R, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody- mediated rejection and transplant glomerulopathy. Transplantation 2012; 94: 172-177. – reference: 19) Ginevri F, Nocera A, Comoli P, et al. Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody mediated rejection. Am J Transplant 2012; 12: 3355-3362. – reference: 17) Everly MJ, Everly JJ, Arend LJ, et al. Reducing de novo donor-specific antibody levels during acute rejection diminishes renal allograft loss. Am J Transplant 2009; 9: 1063-1071. – reference: 13) Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12: 1157-1167. |
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| Snippet | 「I. はじめに」最新のHLA抗体検査技術や免疫抑制剤の進歩により, 急性拒絶反応の発症率の軽減, 短期の移植腎生着率は飛躍的に向上した. しかしながら, 移植腎喪失に陥ってしまった症例の主な廃絶原因は, 慢性抗体関連型拒絶反応(chronic antibody-mediated rejection :... 【Objective】Chronic antibody-mediated rejection (CAMR) is among the most important factors that affect the outcome of kidney allograft. de novo donor-specific... |
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| SubjectTerms | chronic antibody-mediated rejection de novo donor-specific anti-HLA-DQ antibody kidney transplantation |
| Title | 腎臓移植後に産生されるHLA-DQ抗体と慢性抗体関連型拒絶反応の関係について |
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