Association Between HLA Antibodies and Different Sensitization Events in Renal Transplant Candidates

Akgül, Sebahat; Çiftçi, Hayriye Şentürk; Temurhan, Sonay; Çalışkan, Yaşar; Bayraktar, Adem; Tefik, Tzevat; Kaya, İlyas; Canitez, I.O.; Demir, Erol; Yazıcı, Halil; Bakkaloglu, H.; Aydın, Alper; Türkmen, Aydın; Nane, I.; Aydın, Filiz; Oğuz, Fatma

doi:10.1016/j.transproceed.2017.02.004

Cited by 33 publications

(16 citation statements)

References 20 publications

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“…In addition, disease course (7.5 months or more) were related to higher MFI of PRAs for class I; while PLT transfusions (7 or more) were related to higher MFI of PRA for class II. The results were consistent with the findings of previous studies [19][20][21]23 and are useful for haplo-SCT donor selection.…”

Section: Discussionsupporting

confidence: 92%

Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates

Cao

et al. 2020

Sci Rep

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The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) has been recognized as a factor in graft failure (GF) in patients who underwent umbilical cord blood transplantation (UBT), matched unrelated donor transplantation (MUDT), or haploidentical stem cell transplantation (haplo-SCT). Presently, we know little about the prevalence of and risk factors for having anti-HLA antibodies among older transplant candidates. Therefore, we analyzed 273 older patients with hematologic disease who were waiting for haplo-SCT. Among all patients, 73 (26.7%) patients had a positive panelreactive antibody (PRA) result for class I, 38 (13.9%) for class II, and 32 (11.7%) for both. Multivariate analysis showed that females were at a higher risk for having a PRA result for class II (P = 0.001) and for having antibodies against HLA-C and HLA-DQ. Prior pregnancy was a risk factor for having a PRA result for class I (P < 0.001) and for having antibodies against HLA-A, HLA-B and HLA-DQ. Platelet transfusions were risk factors for the following: having a positive PRA result for class I (P = 0.014) and class II (P < 0.001); having antibodies against HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, and HLA-DR; and having higher mean fluorescence intensity (MFI) of PRA for class I (P = 0.042). In addition, previous total transfusions were at high risk for having higher numbers of antibodies to specific HLA loci (P = 0.005), and disease course (7.5 months or more) (P = 0.020) were related to higher MFI of PRAs for class I. Our findings indicated that female sex, prior pregnancy, platelet transfusions and disease courses are independent risk factors for older patients with hematologic disease for having anti-HLA antibodies, which could guide anti-HLA antibody monitoring and be helpful for donor selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recognized as an effective therapy for the majority of malignant hematologic diseases 1-4. However, primary and secondary graft failure (GF) remain a serious complication of allo-HSCT. Multiple factors have been implicated in GF, such as the primary diagnosis, advanced disease status, conditioning regimens, and stem cell dose 5-8. In recent years, the effects of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) have been recognized as a factor in GF 9-11 , either in patients who underwent umbilical cord blood transplantation (UBT), matched unrelated donor transplantation (MUDT), or haploidentical stem cell transplantation (haplo-SCT) 10-16. Therefore, DSAs can influence who is the best donor in HLA-mismatched allo-HSCT settings 17,18. Given the importance of anti-HLA antibodies, there have been many studies focusing on the prevalence and risk factors that may lead to the development of anti-HLA antibodies. Hung et al. 19 found that pregnancy and recent transfusion are independent risk factors for HLA sensitization in patients with end-stage renal disease. Akgul et al. 20 showed that in patients who are waiting for kidney transplantation, sensitiz...

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Section: Discussionsupporting

confidence: 92%

Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates

Cao

et al. 2020

Sci Rep

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“…Several studies, in the transplantation field, have shown that anti-HLA antibody profiles correlate to the rate of allograft rejection [12,55], however, these studies have not explored the role it performs in autoimmune diseases. Between the potential sources of anti-HLA antibodies are blood transfusions, since a probable complication is transfusion-related acute lung injury (TRALI), caused by the anti-HLA Class I and Class II antibodies pre-existents in the plasma donors, where the infused blood stimulates pulmonary endothelial cells and therefore increased capillary permeability [56].…”

Section: Discussionmentioning

confidence: 99%

“…The generation of anti-HLA antibodies is due to different conditions, such as those that have a pathological origin (multiple blood transfusions, kidney, and other organ transplants) [12]. Some studies have found that anti-HLA antibodies, a product of blood transfusion, increases the risk of lung injury and is one of the causes of transfusion-related mortality [13]; moreover, they can also be considered as a product of common physiological conditions (maternal-fetal alloimmunization in multiparous women) [14,15], resulting in microchimerism, which is the persistence of foreign cells in an individual [16].…”

Section: Introductionmentioning

confidence: 99%

Anti-HLA Class II Antibodies Correlate with C-Reactive Protein Levels in Patients with Rheumatoid Arthritis Associated with Interstitial Lung Disease

Ángel-Pablo

Buendía-Roldán

Mejía

et al. 2020

Cells

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The pathogenesis of Rheumatoid Arthritis (RA) is not fully understood, probably influenced by genetic and environmental factors. Interstitial Lung Disease (ILD) is an extra-articular manifestation of RA, which contributes significantly to morbidity and mortality. The identification of anti-HLA antibodies has been useful in the transplantation field; however, its contribution to autoimmune diseases as RA has not been fully studied. We aimed to determine the presence of anti-HLA antibodies in RA patients with and without ILD and its possible association with clinical and biochemical markers. One-hundred and forty-seven RA patients, of which 65 had ILD (RA-ILD group), were included. Sera samples for Anti-HLA Class II LABScreen panel-reactive antibodies (PRA) were analyzed. In both groups, women predominated, and lung function was worse in patients with ILD. The anti-CCP+ (UI/mL) was higher in the RA group in comparison to RA-ILD (p < 0.001). Expositional risk factors (tobacco smoking and biomass-burning smoke) were higher in RA-ILD patients. PRA+ was identified in ~25% RA-ILD patients, while ~29% in the RA group. The CRP levels have a positive correlation with the percentage of reactivity (%PRA, p = 0.02, r2 = 0.60) in the RA-ILD group. In conclusion, anti-HLA antibodies correlate with C-reactive protein levels in RA patients with ILD.

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“…Studies showed that the risk of large increases in donor-specific antibody was greatest when antibodies were originally stimulated by pregnancy than transplant antigens [ 58 ]. Similarly, it has been also reported that the prevalence of anti-HLA antibodies was higher in pregnant women than transplant and transfusion events [ 57 ].…”

Section: Introductionmentioning

confidence: 94%

“…Sensitization by pregnancy has a significant impact on the development of HLA class I and class II antibodies. The rate of developing HLA-B antibodies in patients sensitized by pregnancy was higher compared with sensitization after transfusion [ 57 ]. Studies showed that the risk of large increases in donor-specific antibody was greatest when antibodies were originally stimulated by pregnancy than transplant antigens [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

Alelign

Ahmed

Bobosha

et al. 2018

Journal of Immunology Research

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Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

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Association Between HLA Antibodies and Different Sensitization Events in Renal Transplant Candidates

Cited by 33 publications

References 20 publications

Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates

Prevalence and risk factors of having antibodies to class I and II human leukocyte antigens in older haploidentical allograft candidates

Anti-HLA Class II Antibodies Correlate with C-Reactive Protein Levels in Patients with Rheumatoid Arthritis Associated with Interstitial Lung Disease

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

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