Polymorphisms in CTLA-4 predict de novo donor specific antibody formation after kidney transplantation

Ono, Kosuke; Ide, Kentaro; Kashihara, Mayu; Yamane, Haruki; Akimoto, Shuji; Tanimine, Naoki; Tahara, Hiroyuki; Ohira, Masaichi; Tanaka, Yuka; Ohdan, Hideki

doi:10.1016/j.humimm.2022.03.008

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…These studies suggest that the consequences of these polymorphisms on CTLA-4 functions may be too tenuous to emerge as independent and significant drivers of transplant rejection. Nonetheless, a recent study performed on a small number of patients identified the association of two CTLA-4 polymorphisms with an increased risk of de novo DSA formation over time [35].…”

Section: The Role Of Immune Checkpoints and Their Ligands In Solid Or...mentioning

confidence: 99%

Immune Checkpoints in Solid Organ Transplantation

Del Bello,

Treiner

2023

Biology

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Allogenic graft acceptance is only achieved by life-long immunosuppression, which comes at the cost of significant toxicity. Clinicians face the challenge of adapting the patients’ treatments over long periods to lower the risks associated with these toxicities, permanently leveraging the risk of excessive versus insufficient immunosuppression. A major goal and challenge in the field of solid organ transplantation (SOT) is to attain a state of stable immune tolerance specifically towards the grafted organ. The immune system is equipped with a set of inhibitory co-receptors known as immune checkpoints (ICs), which physiologically regulate numerous effector functions. Insufficient regulation through these ICs can lead to autoimmunity and/or immune-mediated toxicity, while excessive expression of ICs induces stable hypo-responsiveness, especially in T cells, a state sometimes referred to as exhaustion. IC blockade has emerged in the last decade as a powerful therapeutic tool against cancer. The opposite action, i.e., subverting IC for the benefit of establishing a state of specific hypo-responsiveness against auto- or allo-antigens, is still in its infancy. In this review, we will summarize the available literature on the role of ICs in SOT and the relevance of ICs with graft acceptance. We will also discuss the possible influence of current immunosuppressive medications on IC functions.

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Section: The Role Of Immune Checkpoints and Their Ligands In Solid Or...mentioning

confidence: 99%

Immune Checkpoints in Solid Organ Transplantation

Del Bello,

Treiner

2023

Biology

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“…It is expressed on surface of activated T cells and acts as a regulator of the immune response 13 to inhibit cytokine release and down-regulate T cell proliferation 14 . Some studies showed association between CTLA-4 polymorphisms and AR and graft survival 15 , 16 while other didn᾽t 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

Impact of CD 28, CD86, CTLA-4 and PD-1 genes polymorphisms on acute renal allograft rejection and graft survival among Egyptian recipients

Ghoneim,

Sheashaa,

Wafa

et al. 2024

Sci Rep

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To study the impact of four gene polymorphisms on acute renal allograft rejection (AR) and graft survival among Egyptian population. These 4 gene polymorphisms include: (1) CD 28 (rs3116496), (2) CD86 (rs1129055), (3) CTLA-4 (rs3087243), (4) PD-1 (rs2227982). This is a non-concurrent cohort study including 50 kidney transplant recipients diagnosed histopathologically as (AR) [study group] and another 50 matched allograft recipients without AR [control group]. Blood samples were taken from both groups and subjected to genotyping for the selected four genetic polymorphisms by TaqMan genotyping assay. The difference in genotypic distribution of CD 28: rs3116496 and CD86: rs1129055 wasn't statistically significant between the study and control groups (P = 0.22 and 0.33 respectively) and also both polymorphisms had no effect on graft survival (P = 0.36 and 0.74 respectively) while the addition of C allele to IVS3 +17T/C polymorphism in CD28 gene showed a protective effect against AR (P = 0.03). CTLA-4: rs3087243 AG genotype showed a protective effect against AR as it was more frequent in no rejection group compared to those with AR (P = 0.001) with a statistically significant impact on graft survival (P < 0.001), while PD-1: rs2227982 AG genotype was equally distributed between both groups (variant of unknown significance). There was no detected association between CD86 polymorphism: rs1129055 and CD 28 polymorphism: rs3116496 with the development of AR. However, C allele of CD 28 IVS3 +17T/C polymorphism and CTLA-4 polymorphism: rs3087243AG genotype both demonstrated a protective effect against AR.

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