*Purpose: Tertialy lymphoid organs (TLTs) are defined as inducible lymphoid tissues that arise in non-lymphoid organs, and chronic sustained inflammation is one of the most important predisposing factors for the development of TLTs. The purpose of this study was to elucidate the clinical relevance of TLTs in transplanted kidney using two novel strategies. First, to distinguish the effects of TLTs and rejection, we collected and analyzed protocol biopsy samples without evidence of rejection clinically. Second, we defined TLTs using our new TLT staging system we have recently established.

*Methods: From July 2004 to Dec 2014, 204 kidney transplant recipients who underwent living kidney transplantation (KT) at Akita University Hospital were enrolled in this study. After excluding 23 patients with known risk factors for poor graft outcomes such as acute rejection and/or BK polyoma virus associated nephropathy, 181 patients were finally included. Serial protocol biopsy samples, performed at 0-hr, and 1-, 6-, 12-month after KT, were collected and analyzed for the presence and stages of TLTs. A mean age of enrolled patients was 48. Mean eGFR after KT was 65 and 62 at 1-year and 5-year post-transplantation. About one-fourth of patients underwent ABO blood-type incompatible KT, and rituximab with 200 mg/body was administered for these patients preoperatively. TLTs were categorized into different stages; stage I TLTs, defined as the presence of lymphocyte clusters with signs of proliferation, and stage II TLTs, defined as the additional evidence of CD21+ FDCs.

*Results: Although TLTs were found in about 5% of samples in 0-hr biopsy, the prevalence increased to almost 50% at 1-month after KT, and it was maintained at the similar levels for 1-year. Meanwhile, the prevalence of stage II TLTs increased more gradually, from 2% at 1-month to 18% at 1-year post-transplantation. When patients are divided solely by the presence of TLTs, no difference was found in their late graft function between groups. In contrast, when patients are divided by their TLT staging, those with stage II TLTs in 6- or 12-month biopsies showed progressive decline in graft function over the next 5-years, while those with no or stage I TLTs did not. Patients with stage II TLTs in 6- and/or 12-month biopsies showed more severe tubulitis and tubular atrophy scores despite of comparable degree of interstitial inflammation. In subgroup analysis of patients with Banff i score of 0 or 1, the patients with stage II TLTs exhibited progressive graft dysfunction even though the overall degree of interstitial inflammation was mild.

*Conclusions: The prevalence of stage I TLTs abruptly increased in 1-month after KT, whereas that of stage II TLTs increased more gradually. Stage II TLTs predicted progressive graft dysfunction independent from Banff i scores was associated with significant reduction in stage II TLT and B cell clusters.

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