Effect of Fc-γ Receptor Polymorphism on Rituximab-Mediated B Cell Depletion in ABO-Incompatible Adult Living Donor Liver Transplantation

Tanaka, Yuka; Tazawa, Hirofumi; Shimizu, Seiichi; Verma, Sapana; Ohira, Masaichi; Tahara, Hiroyuki; Ide, Kentaro; Ishiyama, K.; Kobayashi, Tsuyoshi; Onoe, Takashi; Ohdan, Hideki

doi:10.1097/txd.0000000000000683

Cited by 16 publications

(19 citation statements)

References 30 publications

(44 reference statements)

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“…Studies indicated that allelic polymorphisms in CD32A may correlate with the efficacy of immunoglobulin-based therapeutics according to their variable affinity for immunoglobulins. It was also suggested that the therapeutic response to rituximab (anti-CD20 monoclonal antibody) [35][36][37] is associated with the CD32A genotype, while FcγRs may have an effect on intravenous IgG-related immunomodulation [37].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Analysis of CD32A and CD16A Polymorphisms in Relation to Autoimmune Responses in Pemphigus Diseases and Subepithelial Autoimmune Blistering Disorders

Gornowicz‐Porowska

Kowalczyk

Seraszek‐Jaros

et al. 2020

Genes

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Autoimmune blistering dermatoses (ABDs) are characterized by autoantibodies to keratinocyte surface antigens and molecules within the dermal–epidermal junction causing disruption of skin integrity. The affinity of Fc receptors (FcRs) causing an autoimmune response in ABDs may vary based on single-nucleotide polymorphisms (SNPs) in FcRs determining the course of disease. This study aimed to explore the effects of CD16A and CD32A SNPs on the autoimmune response in several ABDs. In total, 61 ABDs patients were investigated. ELISA tests, direct immunofluorescence (DIF), TaqMan SNP Genotyping Assays, and statistical analyses were performed. The CA genotype (composed of allele C and A) of rs396991 in CD16A had a higher affinity for tissue-bound IgG1 in pemphigus and for C3 in subepithelial ABDs, showing statistical significance. The greatest relative risk (odds ratio) was reported for AA (rs396991 of CD16A) and CC (rs1801274 of CD32A) homozygotes. There were no statistically significant differences between certain genotypes and specific circulating autoantibodies (anti-DSG1, anti-DSG3 IgG in pemphigus; anti-BP180, anti-BP230 IgG) in subepithelial ABDs. Our findings indicated that rs396991 in CD16A may be of greater importance in ABDs development. Moreover, FcR polymorphisms appeared to have a greater impact on tissue-bound antibodies detected using DIF than circulating serum antibodies in ABDs.

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Section: Discussionmentioning

confidence: 99%

A Comparative Analysis of CD32A and CD16A Polymorphisms in Relation to Autoimmune Responses in Pemphigus Diseases and Subepithelial Autoimmune Blistering Disorders

Gornowicz‐Porowska

Kowalczyk

Seraszek‐Jaros

et al. 2020

Genes

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“…20-22 In organ transplantation, to our knowledge, only one study reported the effect of Fc-γ receptor polymorphism on rituximab-mediated B-cell depletion for complications after ABO-incompatible liver transplantation. 23 The analysis of gene polymorphism also in kidney transplant recipients before desensitization using rituximab may be useful for prediction of the AMR risk after kidney transplantation.…”

Section: Discussionmentioning

confidence: 99%

Association Between Peripheral Blood CD19-Positive Rate and Antibody-Mediated Rejection Following Rituximab Administration in Kidney Transplant Recipients

Nanmoku

Shinzato

Kubo

et al. 2019

Transplantation Direct

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Background. Rituximab is used widely for desensitization in ABO-incompatible and donor-specific antibody-positive kidney transplantation. However, data about the effects of individual differences in rituximab-induced B-cell suppression on antibody-mediated rejection (AMR) remain unknown. We aimed to assess the association between CD19-positive rate and AMR following rituximab administration after kidney transplantation. Methods. Overall, 42 patients who underwent rituximab therapy for pretransplant desensitization in ABO-incompatible (n = 33) and donor-specific antibody-positive (n = 15) kidney transplantation were observed retrospectively. To predict AMR incidence, the peripheral blood CD19-positive rate was determined and classified into short- and long-acting groups. AMR incidence, allograft function, complications, and rituximab dose were compared. Results. Eight patients (19%) had AMR within 39.2 months after transplantation. The CD19-positive rate cutoff value to predict AMR incidence was 4.4%, 6.4%, and 7.7% at 6, 12, and 18 months after transplantation, respectively. When comparing the short- and long-acting groups stratified according to the CD19-positive rate cutoff value, AMR incidence was significantly higher in the short-acting group than in the long-acting group at 6 (71.4% vs 8.6%), 12 (70.0% vs 3.1%), and 18 (58.3% vs 3.3%) months after transplantation. The CD19-positive rate for all patients with AMR exceeded the cutoff value 6, 12, or 18 months. Conversely, serum creatinine level, tacrolimus trough-level, cytomegalovirus antigenemia-positive rate, neutropenia incidence rate, and total dose of rituximab before transplantation showed no significant differences between the 2 groups. Conclusions. The risk of AMR was higher in patients with short-term B-cell suppression following rituximab administration. Additional rituximab administration after transplantation may prevent AMR in patients with a CD19-positive rate higher than the cutoff value.

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“…It has been shown in ABO-incompatible living donor liver transplantation that SNPs of the Fc fragment of IgG receptor (FCGR) gene may influence the risk of infection following Rituximab in this setting. 95 Indeed certain genotypes in this region have also been shown to correlate with clinical and molecular responses to Rituximab in non-Hodgkins lymphoma. 96 The significance of this phenomena on B-cell depletion in renal transplant induction has yet to be established.…”

Section: Induction Therapymentioning

confidence: 99%

Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?

Nobakht

Jagadeesan

Paul

et al. 2021

Transplantation Direct

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Abstract. Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and using prophylactic antimicrobial medications. Graft survival depends on factors beyond human leukocyte antigen matching such as the level of immunosuppression, infections, and management of other comorbidities. Risk stratification of transplant patients based on predisposing genetic modifiers and applying precision pharmacotherapy may help improving the transplant outcomes. Unlike certain fields such as oncology in which consistent attempts are being carried out to move away from the “error and trial approach,” transplant medicine is lagging behind in implementing personalized immunosuppressive therapy. The need for maintaining a precarious balance between underimmunosuppression and overimmunosuppression coupled with adverse effects of medications calls for a gene-based guidance for precision pharmacotherapy in transplantation. Technologic advances in molecular genetics have led to increased accessibility of genetic tests at a reduced cost and have set the stage for widespread use of gene-based therapies in clinical care. Evidence-based guidelines available for precision pharmacotherapy have been proposed, including guidelines from Clinical Pharmacogenetics Implementation Consortium, the Pharmacogenomics Knowledge Base National Institute of General Medical Sciences of the National Institutes of Health, and the US Food and Drug Administration. In this review, we discuss the implications of pharmacogenetics and potential role for genetic variants-based risk stratification in kidney transplantation. A single score that provides overall genetic risk, a polygenic risk score, can be achieved by combining of allograft rejection/loss-associated variants carried by an individual and integrated into practice after clinical validation.

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Effect of Fc-γ Receptor Polymorphism on Rituximab-Mediated B Cell Depletion in ABO-Incompatible Adult Living Donor Liver Transplantation

Abstract: Supplemental digital content is available in the text.

Cited by 16 publications

References 30 publications

A Comparative Analysis of CD32A and CD16A Polymorphisms in Relation to Autoimmune Responses in Pemphigus Diseases and Subepithelial Autoimmune Blistering Disorders

A Comparative Analysis of CD32A and CD16A Polymorphisms in Relation to Autoimmune Responses in Pemphigus Diseases and Subepithelial Autoimmune Blistering Disorders

Association Between Peripheral Blood CD19-Positive Rate and Antibody-Mediated Rejection Following Rituximab Administration in Kidney Transplant Recipients

Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope?

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