Immune Cell Subpopulations in Kidney Transplant Glomerulitis: Composition and Prognosis. (July 2018)

• Record Type: Journal Article
• Authors: Nabokow, Alexander; Khrabrova, Maria; Gröne, Hermann-Josef; Kliem, Volker; Dobronravov, Vladimir; Mukhametdinova, Anastasia
• Is Part Of: Transplantation. Volume 102(2018)Supplement 7S-1
• Publication Date: 2018-07
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/01.tp.0000543293.38475.78
• Languages: English
• ISSNs: 0041-1337

Abstract

Introduction: Kidney 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 methods: In 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 Discussion: CD68+ 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 ( p log-rank =0, 019) as well as CD3+ ≥ 1 ( p log-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 ( p log-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). Figure. No caption available. Figure. No caption available. Conclusion: KTx 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 words: renal transplantation, glomerulitis, monocytes/macrophages, CD68+, donor-specific antibodies Maria Khrabrova had ERA-EDTA Fellowship programm and DAAD grants.