Immune Cell Subpopulations in Kidney Transplant Glomerulitis: Composition and Prognosis.

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IntroductionKidney transplant (KTx) glomerulitis (G) in presence of anti-HLA/MICA/B donor-specific antibodies (DSA) is associated with monocytes/macrophages (CD68+) intracapillar infiltration and considered to be the feature of antibody-mediated rejection. Immune cells subpopulations in DSA-negative G are still poorly investigated. The aim of the study was to assess the association of T-cell (CD3+), CD68+, B-cell (CD20+) infiltrates in glomeruli with long-term KTx survival in patients (Pts) with G including cases without DSA.Materials and methodsIn retrospective study we enrolled 97 KTx recipients with biopsy (Bx) proven G. DSA were evaluated by Luminex at the time of Bx and detected in 25,8% of Pts (DSA+; n=25). In 54,6% of Pts DSA were negative (DSA-; n=53) and unavailable for evaluation in 19 Pts (DSA?). Morphological findings were assessed by Banff 2013 criteria. Intracapillar neutrophils (Neu) were estimated as presence/absence in glomeruli. CD68+, CD3+, CD20+ cells were identified by immunohistochemistry as mean of CD+ cells per non-sclerotic glomerulus (pg) in 92, 77 and 95 available Bx samples, respectively. The Kaplan-Meier death-censored survival plots were used to analyse long-term KTx survival as well as Cox regression models. The independent prognostic variables at first were identified by univariate analysis and those that had a p-value < 0.1 were further analyzed using a multivariate Cox model. Combined graft survival endpoint was defined as return to dialysis or glomerular filtration rate assessed by MDRD formula less than 20 ml/min/1,73m2 at follow-up. Median follow-up was 51 (IQR 8; 72) months.Results and DiscussionCD68+ and CD3+ cells dominated in glomeruli (M (IQR) 4 (2; 8) and 3 (1; 7), respectively). CD20+ were registered with mean less than 1 CD20+ cell pg in 74% of Pts. The intraglomerular CD+ mean cells number was higher in DSA+ group (p=0,005) for CD68+ and did not differ between DSA subgroups for CD3+ and CD20+. Neu were present in 59% of Pts. CD68+ ≥ 8 cells pg was associated with a lower KTx survival (plog-rank=0,019) as well as CD3+ ≥ 1 (plog-rank=0,029) (Figure 1, A-B). Long-term KTx survival was similar either in Pts with and without CD20+ intraglomerular cells (Figure 1, C) or in presence/absence of Neu. In DSA- Pts the difference in KTx survival in CD68+>8 and <8 cells pg subgroups did not reach the statistical significance (plog-rank=0,057) (Figure 1, D). The intracapillar CD68+ infiltration (1 cell pg) was independent predictor of KTx loss in multivariate Cox regression models (p < 0,003) (Figure 2).ConclusionKTx G could be realized by different pathways including anti-HLA DSA independent alloimmune reactions that require further investigations. Immunomorphological evaluation of immune cells, in particular CD68+, could be crucial for long-term KTx prognosis and appropriate therapeutic approach.Key wordsrenal transplantation, glomerulitis, monocytes/macrophages, CD68+, donor-specific antibodiesMaria Khrabrova had ERA-EDTA Fellowship programm and DAAD grants.

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