Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Interferon-γ and its response are determinants of antibody-mediated rejection and clinical outcomes in patients after renal transplantation

Genes & Immunity volume 25, pages 66–81 (2024)Cite this article

Subjects

Abstract

Interferon-γ (IFN-γ) is an important cytokine in tissue homeostasis and immune response, while studies about it in antibody-mediated rejection (ABMR) are very limited. This study aims to comprehensively elucidate the role of IFN-γ in ABMR after renal transplantation. In six renal transplantation cohorts, the IFN-γ responses (IFNGR) biological process was consistently top up-regulated in ABMR compared to stable renal function or even T cell-mediated rejection in both allografts and peripheral blood. According to single-cell analysis, IFNGR levels were found to be broadly elevated in most cell types in allografts and peripheral blood with ABMR. In allografts with ABMR, M1 macrophages had the highest IFNGR levels and were heavily infiltrated, while kidney resident M2 macrophages were nearly absent. In peripheral blood, CD14+ monocytes had the top IFNGR level and were significantly increased in ABMR. Immunofluorescence assay showed that levels of IFN-γ and M1 macrophages were sharply elevated in allografts with ABMR than non-rejection. Importantly, the IFNGR level in allografts was identified as a strong risk factor for long-term renal graft survival. Together, this study systematically analyzed multi-omics from thirteen independent cohorts and identified IFN-γ and IFNGR as determinants of ABMR and clinical outcomes in patients after renal transplantation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flowchart of this study.
Fig. 2: Enrichment analysis of allograft kidney and peripheral blood samples with STA, ABMR, and TCMR.
Fig. 3: Correlation of immune cell infiltration and immune-related gene expressions with IFNGR levels.
Fig. 4: Characterization of allograft kidney single-cell RNA-seq data.
Fig. 5: IFNGR levels and IFN-γ signaling analysis of allograft kidney single-cell RNA-seq data.
Fig. 6: Characterization of mononuclear phagocyte subtypes by single-cell RNA-seq data of allograft kidney.
Fig. 7: Circulating immune cell landscape of CK and ABMR recipients.
Fig. 8: IFNGR levels and IFN-γ signaling analysis of peripheral blood single-cell RNA-seq data.
Fig. 9: Mononuclear phagocyte patterns in peripheral blood of ABMR and non-ABMR patients.
Fig. 10: Immunofluorescent staining of IFN-γ and M1 macrophage in ABMR.
Fig. 11: Prognostic assessment of IFNGR and IFN-γ-related genes on kidney recipients.

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725–30.

    CAS  PubMed  Google Scholar 

  2. Hariharan S, Israni AK, Danovitch G. Long-Term Survival after Kidney Transplantation. N Engl J Med. 2021;385:729–43.

    CAS  PubMed  Google Scholar 

  3. Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transpl. 2009;9:2520–31.

    CAS  Google Scholar 

  4. Willicombe M, Roufosse C, Brookes P, Galliford JW, McLean AG, Dorling A, et al. Antibody-mediated rejection after alemtuzumab induction: incidence, risk factors, and predictors of poor outcome. Transplantation. 2011;92:176–82.

    CAS  PubMed  Google Scholar 

  5. Lucas JG, Co JP, Nwaogwugwu UT, Dosani I, Sureshkumar KK. Antibody-mediated rejection in kidney transplantation: an update. Expert Opin Pharm. 2011;12:579–92.

    CAS  Google Scholar 

  6. Schinstock CA, Mannon RB, Budde K, Chong AS, Haas M, Knechtle S, et al. Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group. Transplantation. 2020;104:911–22.

    PubMed  PubMed Central  Google Scholar 

  7. Velidedeoglu E, Cavaillé-Coll MW, Bala S, Belen OA, Wang Y, Albrecht R. Summary of 2017 FDA Public Workshop: Antibody-mediated Rejection in Kidney Transplantation. Transplantation. 2018;102:e257–64.

    PubMed  Google Scholar 

  8. Burton SA, Amir N, Asbury A, Lange A, Hardinger KL. Treatment of antibody-mediated rejection in renal transplant patients: a clinical practice survey. Clin Transpl. 2015;29:118–23.

    CAS  Google Scholar 

  9. Sautenet B, Blancho G, Büchler M, Morelon E, Toupance O, Barrou B, et al. One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial. Transplantation. 2016;100:391–9.

    CAS  PubMed  Google Scholar 

  10. Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, et al. A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection. J Am Soc Nephrol. 2018;29:591–605.

    CAS  PubMed  Google Scholar 

  11. Cornell LD, Schinstock CA, Gandhi MJ, Kremers WK, Stegall MD. Positive crossmatch kidney transplant recipients treated with eculizumab: outcomes beyond 1 year. Am J Transpl. 2015;15:1293–302.

    CAS  Google Scholar 

  12. Gill RG, Lin CM. Linking innate immunity and chronic antibody-mediated allograft rejection. Curr Opin Organ Tran. 2019;24:694–8.

    CAS  Google Scholar 

  13. Usuelli V, Loretelli C, Seelam AJ, Pastore I, D’Addio F, Ben NM, et al. Novel Soluble Mediators of Innate Immune System Activation in Solid Allograft Rejection. Transplantation. 2022;106:500–9.

    CAS  PubMed  Google Scholar 

  14. Ivashkiv LB. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nat Rev Immunol. 2018;18:545–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hu X, Ivashkiv LB. Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases. Immunity. 2009;31:539–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749–95.

    CAS  PubMed  Google Scholar 

  17. McLaren JE, Ramji DP. Interferon gamma: a master regulator of atherosclerosis. Cytokine Growth F R. 2009;20:125–35.

    CAS  Google Scholar 

  18. Famulski KS, Einecke G, Reeve J, Ramassar V, Allanach K, Mueller T, et al. Changes in the transcriptome in allograft rejection: IFN-gamma-induced transcripts in mouse kidney allografts. Am J Transpl. 2006;6:1342–54.

    CAS  Google Scholar 

  19. Kong D, Huang S, Miao X, Li J, Wu Z, Shi Y, et al. The dynamic cellular landscape of grafts with acute rejection after heart transplantation. J Heart Lung Transpl. 2023;42:160–72.

    Google Scholar 

  20. Reeve J, Böhmig GA, Eskandary F, Einecke G, Lefaucheur C, Loupy A, et al. Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes. JCI Insight. 2017;2:e94197.

    PubMed  PubMed Central  Google Scholar 

  21. Reeve J, Sellarés J, Mengel M, Sis B, Skene A, Hidalgo L, et al. Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies. Am J Transpl. 2013;13:645–55.

    CAS  Google Scholar 

  22. Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, et al. Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study. Am J Transpl. 2013;13:2352–63.

    CAS  Google Scholar 

  23. Broin P Ó, Hayde N, Bao Y, Ye B, Calder RB, de Boccardo G, et al. A pathogenesis-based transcript signature in donor-specific antibody-positive kidney transplant patients with normal biopsies. Genom Data. 2014;2:357–60.

    Google Scholar 

  24. Van Loon E, Lamarthée B, de Loor H, Van Craenenbroeck AH, Brouard S, Danger R, et al. Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology. Kidney Int. 2022;102:183–95.

    PubMed  PubMed Central  Google Scholar 

  25. Van Loon E, Gazut S, Yazdani S, Lerut E, de Loor H, Coemans M, et al. Development and validation of a peripheral blood mRNA assay for the assessment of antibody-mediated kidney allograft rejection: A multicentre, prospective study. Ebiomedicine. 2019;46:463–72.

    PubMed  PubMed Central  Google Scholar 

  26. Einecke G, Reeve J, Sis B, Mengel M, Hidalgo L, Famulski KS, et al. A molecular classifier for predicting future graft loss in late kidney transplant biopsies. J Clin Invest. 2010;120:1862–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang W, Yi Z, Wei C, Keung KL, Sun Z, Xi C, et al. Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection. JCI Insight. 2019;4:e127543.

    PubMed  PubMed Central  Google Scholar 

  28. Hrubá P, Brabcová I, Gueler F, Krejčík Z, Stránecký V, Svobodová E, et al. Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes. Kidney Int. 2015;88:785–95.

    PubMed  Google Scholar 

  29. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27:1739–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Hu FF, Liu CJ, Liu LL, Zhang Q, Guo AY. Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response. Brief Bioinform. 2021;22:bbaa176.

    PubMed  Google Scholar 

  32. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Campbell KS, Purdy AK. Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations. Immunology. 2011;132:315–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Afrache H, Gouret P, Ainouche S, Pontarotti P, Olive D. The butyrophilin (BTN) gene family: from milk fat to the regulation of the immune response. Immunogenetics. 2012;64:781–94.

    CAS  PubMed  Google Scholar 

  35. Suryawanshi H, Yang H, Lubetzky M, Morozov P, Lagman M, Thareja G, et al. Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts. Plos One. 2022;17:e0267704.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Kong F, Ye S, Zhong Z, Zhou X, Zhou W, Liu Z, et al. Single-Cell Transcriptome Analysis of Chronic Antibody-Mediated Rejection After Renal Transplantation. Front Immunol. 2021;12:767618.

    PubMed  Google Scholar 

  37. Hao Y, Hao S, Andersen-Nissen E, Mauck WR, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184:3573–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16:1289–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Zheng L, Qin S, Si W, Wang A, Xing B, Gao R, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2021;374:abe6474.

    PubMed  Google Scholar 

  40. Trapnell C, Cacchiarelli D, Grimsby J, Pokharel P, Li S, Morse M, et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat Biotechnol. 2014;32:381–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, et al. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021;12:1088.

    CAS  PubMed  PubMed Central  ADS  Google Scholar 

  42. De Benedetti F, Prencipe G, Bracaglia C, Marasco E, Grom AA. Targeting interferon-γ in hyperinflammation: opportunities and challenges. Nat Rev Rheumatol. 2021;17:678–91.

    PubMed  Google Scholar 

  43. Hidalgo LG, Sis B, Sellares J, Campbell PM, Mengel M, Einecke G, et al. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection. Am J Transpl. 2010;10:1812–22.

    CAS  Google Scholar 

  44. Montgomery RA, Zachary AA, Racusen LC, Leffell MS, King KE, Burdick J, et al. Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients. Transplantation. 2000;70:887–95.

    CAS  PubMed  Google Scholar 

  45. Rocha PN, Butterly DW, Greenberg A, Reddan DN, Tuttle-Newhall J, Collins BH, et al. Beneficial effect of plasmapheresis and intravenous immunoglobulin on renal allograft survival of patients with acute humoral rejection. Transplantation. 2003;75:1490–5.

    CAS  PubMed  Google Scholar 

  46. Böhmig GA, Wahrmann M, Regele H, Exner M, Robl B, Derfler K, et al. Immunoadsorption in severe C4d-positive acute kidney allograft rejection: a randomized controlled trial. Am J Transpl. 2007;7:117–21.

    Google Scholar 

  47. Lefaucheur C, Nochy D, Andrade J, Verine J, Gautreau C, Charron D, et al. Comparison of combination Plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transpl. 2009;9:1099–107.

    CAS  Google Scholar 

  48. Loupy A, Lefaucheur C. Antibody-Mediated Rejection of Solid-Organ Allografts. N Engl J Med. 2018;379:1150–60.

    CAS  PubMed  Google Scholar 

  49. Asderakis A, Sankaran D, Dyer P, Johnson RW, Pravica V, Sinnott PJ, et al. Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: the cytokine effect on transplantation. Transplantation. 2001;71:674–7.

    CAS  PubMed  Google Scholar 

  50. Awad M, Pravica V, Perrey C, El GA, Yonan N, Sinnott PJ, et al. CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis. Hum Immunol. 1999;60:343–6.

    CAS  PubMed  Google Scholar 

  51. Jackson SW, Jacobs HM, Arkatkar T, Dam EM, Scharping NE, Kolhatkar NS, et al. B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6. J Exp Med. 2016;213:733–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Domeier PP, Chodisetti SB, Soni C, Schell SL, Elias MJ, Wong EB, et al. IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity. J Exp Med. 2016;213:715–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, et al. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transpl. 2020;20:2318–31.

    CAS  Google Scholar 

  54. Sablik KA, Jordanova ES, Pocorni N, Clahsen-van GM, Betjes M. Immune Cell Infiltrate in Chronic-Active Antibody-Mediated Rejection. Front Immunol. 2019;10:3106.

    CAS  PubMed  Google Scholar 

  55. Lin SL, Li B, Rao S, Yeo EJ, Hudson TE, Nowlin BT, et al. Macrophage Wnt7b is critical for kidney repair and regeneration. P Natl Acad Sci USA. 2010;107:4194–9.

    CAS  ADS  Google Scholar 

  56. Schmidt IM, Hall IE, Kale S, Lee S, He CH, Lee Y, et al. Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function. J Am Soc Nephrol. 2013;24:309–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Sola A, Weigert A, Jung M, Vinuesa E, Brecht K, Weis N, et al. Sphingosine-1-phosphate signalling induces the production of Lcn-2 by macrophages to promote kidney regeneration. J Pathol. 2011;225:597–608.

    CAS  PubMed  Google Scholar 

  58. Callemeyn J, Lamarthée B, Koenig A, Koshy P, Thaunat O, Naesens M. Allorecognition and the spectrum of kidney transplant rejection. Kidney Int. 2022;101:692–710.

    CAS  PubMed  Google Scholar 

  59. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Panzer SE. Macrophages in Transplantation: A Matter of Plasticity, Polarization, and Diversity. Transplantation. 2022;106:257–67.

    PubMed  PubMed Central  ADS  Google Scholar 

  61. Schinstock CA, Stegall M, Cosio F. New insights regarding chronic antibody-mediated rejection and its progression to transplant glomerulopathy. Curr Opin Nephrol Hy. 2014;23:611–8.

    CAS  Google Scholar 

  62. Toki D, Zhang W, Hor KL, Liuwantara D, Alexander SI, Yi Z, et al. The role of macrophages in the development of human renal allograft fibrosis in the first year after transplantation. Am J Transpl. 2014;14:2126–36.

    CAS  Google Scholar 

  63. Nash WT, Okusa MD. Chess Not Checkers: Complexities Within the Myeloid Response to the Acute Kidney Injury Syndrome. Front Med-Lausanne. 2021;8:676688.

    PubMed  PubMed Central  Google Scholar 

  64. Uderhardt S, Martins AJ, Tsang JS, Lämmermann T, Germain RN. Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage. Cell. 2019;177:541–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Narasimhan PB, Marcovecchio P, Hamers A, Hedrick CC. Nonclassical Monocytes in Health and Disease. Annu Rev Immunol. 2019;37:439–56.

    CAS  PubMed  Google Scholar 

  66. Ng CT, Fong LY, Sulaiman MR, Moklas MA, Yong YK, Hakim MN, et al. Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration. J Inter Cytok Res. 2015;35:513–22.

    CAS  Google Scholar 

  67. Stolpen AH, Guinan EC, Fiers W, Pober JS. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol. 1986;123:16–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Osickova K, Hruba P, Kabrtova K, Klema J, Maluskova J, Slavcev A, et al. Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization. Front Med Lausanne. 2021;8:780636.

    PubMed  PubMed Central  Google Scholar 

  69. Turgeon NA, Kirk AD, Iwakoshi NN. Differential effects of donor-specific alloantibody. Transpl Rev Orlan. 2009;23:25–33.

    Google Scholar 

  70. Viglietti D, Lefaucheur C, Glotz D. Evidence for an important role of both complement-binding and noncomplement-binding donor-specific antibodies in renal transplantation. Curr Opin Organ Tran. 2016;21:433–40.

    CAS  Google Scholar 

  71. El-Awar N, Jucaud V, Nguyen A. HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined. J Immunol Res. 2017;2017:3406230.

    PubMed  PubMed Central  Google Scholar 

  72. Duquesnoy RJ. HLA epitope based matching for transplantation. Transpl Immunol. 2014;31:1–6.

    CAS  PubMed  Google Scholar 

  73. Konvalinka A, Tinckam K. Utility of HLA Antibody Testing in Kidney Transplantation. J Am Soc Nephrol. 2015;26:1489–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Tait BD. Detection of HLA Antibodies in Organ Transplant Recipients - Triumphs and Challenges of the Solid Phase Bead Assay. Front Immunol. 2016;7:570.

    PubMed  PubMed Central  Google Scholar 

  75. Buatois V, Chatel L, Cons L, Lory S, Richard F, Guilhot F, et al. Use of a mouse model to identify a blood biomarker for IFNγ activity in pediatric secondary hemophagocytic lymphohistiocytosis. Transl Res. 2017;180:37–52.

    CAS  PubMed  Google Scholar 

  76. Lortat-Jacob H, Baltzer F, Grimaud JA. Heparin decreases the blood clearance of interferon-gamma and increases its activity by limiting the processing of its carboxyl-terminal sequence. J Biol Chem. 1996;271:16139–43.

    CAS  PubMed  Google Scholar 

  77. Rutenfranz I, Kirchner H. Pharmacokinetics of recombinant murine interferon-gamma in mice. J Interferon Res. 1988;8:573–80.

    CAS  PubMed  Google Scholar 

  78. Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, et al. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N. Engl J Med. 2020;382:1811–22.

    PubMed  Google Scholar 

  79. Hommes DW, Mikhajlova TL, Stoinov S, Stimac D, Vucelic B, Lonovics J, et al. Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn’s disease. Gut. 2006;55:1131–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Reinisch W, de Villiers W, Bene L, Simon L, Rácz I, Katz S, et al. Fontolizumab in moderate to severe Crohn’s disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm Bowel Dis. 2010;16:233–42.

    PubMed  Google Scholar 

  81. Boedigheimer MJ, Martin DA, Amoura Z, Sánchez-Guerrero J, Romero-Diaz J, Kivitz A, et al. Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis. Lupus Sci Med. 2017;4:e000226.

    PubMed  PubMed Central  Google Scholar 

  82. Chen P, Vu T, Narayanan A, Sohn W, Wang J, Boedigheimer M, et al. Pharmacokinetic and pharmacodynamic relationship of AMG 811, an anti-IFN-γ IgG1 monoclonal antibody, in patients with systemic lupus erythematosus. Pharm Res Dordr. 2015;32:640–53.

    CAS  Google Scholar 

  83. Kobayashi T, Hibi T. Improving IBD outcomes in the era of many treatment options. Nat Rev Gastro Hepat. 2023;20:79–80.

    Google Scholar 

Download references

Funding

This work was supported by the General Program of the National Natural Science Foundation of China (NSFC) (81970645, 82000711, 82170766) and the joint fund of the Beijing Municipal Commission of Education and Natural Science Foundation of Beijing Municipality (KZ202010025036).

Author information

Author notes

  1. These authors contributed equally: Hao Zhang, Di Zhang, Yue Xu.

Authors and Affiliations

  1. Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

    Hao Zhang, Di Zhang, Yue Xu, He Zhang, Zijian Zhang & Xiaopeng Hu

  2. Institute of Urology, Capital Medical University, Beijing, China

    Hao Zhang, Di Zhang, Yue Xu, He Zhang, Zijian Zhang & Xiaopeng Hu

Authors
  1. Hao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Di Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yue Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. He Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zijian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaopeng Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the manuscript. Hao Zhang, DZ, ZZ, and XH designed the study. Hao Zhang and YX performed the bulk data analysis and DZ conducted the single-cell data analysis. Hao Zhang and DZ drew the figures. Hao Zhang and He Zhang collected the patient information. DZ conducted the immunofluorescence staining experiment. Hao Zhang drafted the manuscript. YX, DZ, ZZ, and XH revised the manuscript. YX provided clinical suggestions and feedback for the study. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Zijian Zhang or Xiaopeng Hu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All procedures were performed strictly in compliance with the Declaration of Helsinki 1964 or equivalent ethical principles. The research protocol was approved by the Ethics Committee of Beijing Chao-Yang Hospital (Approval number 2023-科-16). All patients involved in this study had given their informed consent before the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, H., Zhang, D., Xu, Y. et al. Interferon-γ and its response are determinants of antibody-mediated rejection and clinical outcomes in patients after renal transplantation. Genes Immun 25, 66–81 (2024). https://doi.org/10.1038/s41435-024-00254-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41435-024-00254-x

Search

Advanced search

Quick links