Relationship of donor-specific class-I anti-HLA antibodies detected by ELISA after kidney transplantation on the development of acute rejection and graft survival

Aim. Determination of diagnostic significance of pro − and anti-inflammatory cytokines in early prognosis of posttransplant renal failure in patients with chronic renal disease.Materials and methods. In the peripheral blood of patients with chronic kidney disease 6 hours before kidney transplantation, multiplex analysis using Simplex ProcartaPlex panel (Bioscience, USA) and xMAP technology (principle of flow cytometry) was used to estimate the content of 10 cytokines: 7 proinflammatory (IL-1b, IL-6, IL-12p70, IL-27, IL-17A, IL-18) and 3 antiinflammatory (IL-1RA, IL-4, IL-13). Identification of HLA-antibodies was carried out with the help of multiplex immunological analysis, using test systems (Gen-Prob, USA), flow analyzer Luminex 200 xMAP technology (bimolecular reactions on the surface of microspheres).Results. The limited diagnostic significance of HLA-antibodies is due to the fact that their detection in the posttransplantation period can be either in the development of acute graft rejection, or in the favorable course of the period after the operation. Meanwhile, the determination of a number of blood cytokines before kidney transplantation allows predicting post-transplantation rejection. In particular, certain criteria favorable course of the period after kidney transplantation by absence of HLA antibodies in patients with chronic renal failure can be considered as the initial (within 6 hours of transplantation) low levels of IL1β, IL6, IL17а. Prognostically the increase in the blood levels of proinflammatory cytokines − IL6, IL17a and anti-inflammatory IL1-RA is a significant marker of acute rejection of a transplanted kidney. Along with this, it is important to note that the appearance of HLA antibodies in patients with a favorable course of the post-transplantation period is associated with an initially elevated level of proinflammatory cytokines such as Il1ß and IL6.Conclusion. Diagnostic value of the evaluated cytokines at the pre-transplant kidney patients determines the feasibility of the inclusion of evaluation of the serum concentration of IL1β, IL6, IL17a, IL1-RA in the programme of pre-transplant laboratory tests .

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P1609HLA EPITOPE MATCHING IN KIDNEY TRANSPLANTATION AND PRACTICAL APPLICATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1609 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Irena Rambabova Bushljetikj ◽

Goce Spasovski ◽

Koco Dimitrovski

Keyword(s):

Kidney Transplantation ◽

Amino Acid ◽

Acute Rejection ◽

Amino Acid Sequences ◽

Class I ◽

Hla Dr ◽

Increased Risk ◽

Class 1 ◽

Unrelated Donors ◽

Hla Mismatches

Abstract Background and Aims HLA compatibility between donor and recipient is an important factor that influences graft outcomes after kidney transplantation. Increasing number of class I (HLA-AB) and class II (HLA-DR) mismatches are associated with an increased risk of acute rejection and graft loss. Recent developments have increased our understanding of the structural basis of HLA antigenicity and may allow accurate evaluation of the immunogenic potential of broad antigen HLA mismatches. The immunogenicity of HLA antigens is determined by continuous and discontinuous short sequences of amino acids that form the antibody-accessible regions within each HLA allele known as epitopes. HLAMatchmaker, a computer algorithm that calculates the number of epitope mismatches between donors and recipients by considering each HLA allele as a combination of distinct epitopes known as triplets (continuous amino acid sequences) or eplets (closely located contiguous amino acid sequences). Method A total number of 55 adult patients with LDKT were included in the study. The inclusion criteria: first transplantation of one organ - kidney, use of living donor related or unrelated, emotionally related (spouses) donor. Data concerning donor - sex, age of the donor, type of donation (related or unrelated donor), and data concerning the recipients: sex, age, hemodialysis vintage, underlying disease, type of immunosuppressive therapy, were analyzed. The number of eplet HLA mismatches for each recipient and donor pair at HLA class I (HLA-AB) and class II (HLA-DR) loci was calculated using HLAMatchmaker (Version 1.2) Results In our study we have included 55 patients. 44 patients have related and 11 have unrelated donors. From the group of related donors 31 patients were haploidentycal, with 3 HLA miss match, in the group of unrelated donors-recipients 5 of them have 6 miss match. According HLA MM triplets Class 1 + 2 < or> 20 we have devided 2 groups, but no statistical difference on the graft function was observed in the follow up period. Three acute rejections were reported in the group of patients with HLA miss match triplets Class 1 + 2> 20. Conclusion An increasing number of epitope HLA mismatches is associated with an increased risk of acute rejection. Triplet HLA mismatches may provide better risk stratification for acute rejection and graft survival among those who are otherwise classified as low immunological risk at the broad antigen level.

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Combined Immunotherapy With Belatacept and BTLA Overexpression Attenuates Acute Rejection Following Kidney Transplantation

Frontiers in Immunology ◽

10.3389/fimmu.2021.618737 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hengcheng Zhang ◽

Zijie Wang ◽

Jiayi Zhang ◽

Zeping Gui ◽

Zhijian Han ◽

...

Keyword(s):

Immune Response ◽

Kidney Transplantation ◽

Acute Rejection ◽

Serum Creatinine ◽

Graft Survival ◽

Rat Kidney ◽

Combined Therapy ◽

Graft Function ◽

Kidney Graft ◽

Term Survival

BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and MethodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

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BELATACEPT COMBINED WITH BTLA PROLONG ALLOGENEIC KIDNEY GRAFT SURVIVAL AND INHIBITED ACUTE REJECTION AFTER KIDNEY TRANSPLANTATION

Transplantation Journal ◽

10.1097/01.tp.0000700260.71556.f2 ◽

2020 ◽

Vol 104 (S3) ◽

pp. S342-S342

Author(s):

Hengcheng Zhang ◽

Hao Chen ◽

Li Sun ◽

Zijie Wang ◽

Zhijian Han ◽

...

Keyword(s):

Kidney Transplantation ◽

Acute Rejection ◽

Graft Survival ◽

Kidney Graft

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HLA Class I Antibodies in Patients Awaiting Kidney Transplantation and the Association With Renal Graft Survival

Transplantation Proceedings ◽

10.1016/j.transproceed.2008.07.043 ◽

2008 ◽

Vol 40 (7) ◽

pp. 2191-2194 ◽

Cited By ~ 2

Author(s):

H.-H. Wu ◽

Y.-C. Tien ◽

C.-I. Huang ◽

Y.-J. Chiang ◽

S.-H. Chu ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Survival ◽

Hla Class I ◽

Class I ◽

Renal Graft ◽

Renal Graft Survival

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Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis

AIDS Research and Therapy ◽

10.1186/s12981-019-0253-z ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 2

Author(s):

Xin Zheng ◽

Lian Gong ◽

Wenrui Xue ◽

Song Zeng ◽

Yue Xu ◽

...

Keyword(s):

Systematic Review ◽

Kidney Transplantation ◽

Antiretroviral Therapy ◽

Acute Rejection ◽

Kidney Transplant ◽

Graft Survival ◽

Patient Survival ◽

Meta Analysis ◽

Infectious Complications ◽

Hiv Positive

Abstract Background Kidney transplantation is now a viable alternative to dialysis in HIV-positive patients who achieve good immunovirological control with the currently available antiretroviral therapy regimens. This systematic review and meta-analysis investigate the published evidence of outcome and risk of kidney transplantation in HIV-positive patients following the PRISMA guidelines. Methods Searches of PubMed, the Cochrane Library and EMBASE identified 27 cohort studies and 1670 case series evaluating the survival of HIV-positive kidney transplant patients published between July 2003 and May 2018. The regimens for induction, maintenance therapy and highly active antiretroviral therapy, acute rejection, patient and graft survival, CD4 count and infectious complications were recorded. We evaluated the patient survival and graft survival at 1 and 3 years respectively, acute rejection rate and also other infectious complications by using a random-effects analysis. Results At 1 year, patient survival was 0.97 (95% CI 0.95; 0.98), graft survival was 0.91 (95% CI 0.88; 0.94), acute rejection was 0.33 (95% CI 0.28; 0.38), and infectious complications was 0.41 (95% CI 0.34; 0.50), and at 3 years, patient survival was 0.94 (95% CI 0.90; 0.97) and graft survival was 0.81 (95% CI 0.74; 0.87). Conclusions With careful selection and evaluation, kidney transplantation can be performed with good outcomes in HIV-positive patients.

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