Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients
Institutional Repositories DataBase (IRDB), vol. 33, pp. 186–200
Abstract
[Background:] Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the impacts of TLTs on future graft function using our histological TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs. [Methods:] Serial protocol biopsy samples (0-hour, 1-, 6-, and 12-months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. [Results:] Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared to patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pre-transplantation rituximab treatment dramatically attenuated the development of stage II TLTs. [Conclusions:] TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.
Authors 13
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Kyoto University · CHA University Bundang Medical Center · CHA University
Affiliation as printed
Department of Nephrology, Graduate School of Medicine, Kyoto University; Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University
Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
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Affiliation as printed
Department of Nephrology, Graduate School of Medicine, Kyoto University; Medical Innovation Center TMK Project, Graduate School of Medicine, Kyoto University
Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Medical Innovation Center TMK Project, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Affiliation as printed
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University
Department of Urology, Graduate School of Medicine, Akita University
Department of Urology, Graduate School of Medicine, Akita University, Akita, Japan
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Affiliation as printed
Human Health Sciences, Graduate School of Medicine, Kyoto University
Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Affiliation as printed
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University
Department of Urology, Graduate School of Medicine, Akita University
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan
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Affiliation as printed
Department of Nephrology, Graduate School of Medicine, Kyoto University; Medical Innovation Center TMK Project, Graduate School of Medicine, Kyoto University
Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Medical Innovation Center TMK Project, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Affiliation as printed
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan
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Akita University · Akita University Hospital
Affiliation as printed
Center for Kidney Disease and Transplantation, Akita University Hospital
Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Japan
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Akita University · Akita University Hospital
Affiliation as printed
Center for Kidney Disease and Transplantation, Akita University Hospital
Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, Japan
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Affiliation as printed
Division of Nephrology, Department of Internal Medicine, Kyung Hee University
Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Republic of Korea
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Affiliation as printed
Division of Nephrology, RWTH University of Aachen; Electron Microscopy Facility, RWTH University of Aachen; Institute of Pathology, RWTH University of Aachen
Division of Nephrology, RWTH University of Aachen, Germany, Aachen, Germany
Electron Microscopy Facility, RWTH University of Aachen, Aachen, Germany
Institute of Pathology, RWTH University of Aachen, Germany, Aachen, Germany
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Affiliation as printed
Department of Urology, Graduate School of Medicine, Akita University
Department of Urology, Graduate School of Medicine, Akita University, Akita, Japan
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Motoko Yanagita corresponding
Affiliation as printed
Department of Nephrology, Graduate School of Medicine, Kyoto University; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University
Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan