Anti-human Leukocyte Antigen Antibodies Research Articles

Acute mixed-lineage leukemia treated with desensitization therapy prior to HLA-haploidentical transplantation with high donor-specific antibodies.

A 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, who had a 5/8 HLA haploidentical match. However, the patient had donor-specific antibodies against the donor's HLA-B 0702 and HLA-C 0702. To address this issue, after rituximab therapy, the patient was given platelet transfusions from B0702- and C0702-positive donors on day - 1 and day 0, and immunoglobulin on day 0, followed by PBSCT. Donor-specific antibodies decreased by over 90%, and engraftment was confirmed on day 13. Since then, the patient has remained relapse-free and healthy. This case suggests that appropriate management of donor-specific antibodies can enable safe transplantation, even in donors who test positive for these antibodies.

Lymphocyte Crossmatch Testing or Donor HLA-DP and -DQ Allele Typing Effectiveness in Single Cord Blood Transplantation for Patients With Anti-HLA Antibodies Other Than Against HLA-A, -B, -C, and -DRB1

Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT). The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and -DQ typing of CB units in improving transplant outcomes. We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n = 58), lymphocyte crossmatch testing (n = 32) or additional HLA-DP/-DQ alleles typing of CB (n = 15) was performed to avoid the use of units with corresponding alleles. The median patient age was 57 years (16 to 77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and >80% were heavily transfused. Two hundred twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (Group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, -C, and -DRB1 (Group B). No patients in both Groups A and B exhibited donor-specific anti-HLA antibodies against HLA-A, -B, -C, and -DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% versus 94.1%), whereas nonrelapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% versus 4.9%). In patients who received 2 or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% versus 93.8%) (P = .049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to 2-year overall survival (OS) (43.1% versus 52.3%) and NRM (44.0% versus 30.7%) than in the antibody-negative patients. In contrast, the results of Group B were comparable to those of the antibodies-negative patients, while the results of Group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%). The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be useful strategies to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

Antibody-mediated rejection (AMR) in pediatric lung transplantation-Current state and future directions.

Lung transplantation is considered as the ultimate therapy for children with advanced pulmonary disease. International data show a median conditional 1-year post-transplantation survival of 9.1 years. Recently, antibody-mediated rejection (AMR) has increasingly been recognized as an important cause of allograft dysfunction although pediatric reports are still scarce. Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) are known to play a role in AMR development post-transplant but AMR pathogenesis is still poorly understood. Central to the concept of pulmonary AMR is immune activation with the production of allo-specific B-cells and plasma cells directed against donor lung antigens. The frequency of pulmonary AMR in children is currently unknown. Due to the lack of AMR data in children, the diagnostic approach for pediatric pulmonary AMR is solely based on adult literature. This personal viewpoint article evaluates the rational for the creation of age-based thresholds for different diagnostic categories of pulmonary AMR and data on the management of pulmonary AMR in children. To the authors' knowledge, there have been no randomized controlled trials comparing different management regimes in pulmonary AMR, and thus, management and treatment algorithms for pulmonary AMR in children are only extrapolated from adults. To advance the knowledge of AMR in children, the authors propose that children be included in collaborative, multi-center trials. It is vital that future decisions on internationally agreed upon guidelines for pulmonary AMR take its impact on children into consideration. Research is needed to fill the current knowledge gaps in the field of pulmonary AMR in children focused on optimizing outcomes.

Dynamics of HLA and angiotensin II type 1 receptor antibodies during pregnancy

BackgroundAlloantibodies, especially anti-human leukocyte antigen antibodies (HLA antibodies), and autoantibodies, as angiotensin II type 1 receptor antibodies (AT1R antibodies), may complicate the access and the course of transplantation. Pregnancy is a known source of HLA antibodies, with most studies evaluating pregnancy-induced sensitization by complement-dependent cytotoxicity assays, mainly after childbirth. AT1R antibodies have been evaluated in the context of preeclampsia. We aimed to evaluate pregnancy as a natural source of HLA antibodies and AT1R antibodies, their dynamics along gestation and the potential factors involved in antibody appearance. MethodsSerum samples from pregnant women were collected during the three trimesters of pregnancy (1T, 2T, 3T). Presence of HLA antibodies was assessed by screening beads on Luminex and AT1R antibodies by ELISA. ResultsA cohort of 138 pregnant women were included. Samples from all were tested in 1T, 127 in 2T and 102 in 3T. HLA antibodies increased from 29.7 % (1T) to 38.2 % (3T). AT1R antibodies were stable around 30 % along pregnancy. Up to 43.2 % multiparous women had HLA antibodies, with a similar proportion of class I and class II antibodies. In primiparous women HLA antibodies increased along pregnancy (from 17.6 % to 34.1 %), with predominance of class II HLA antibodies. AT1R antibodies were not different in primiparous and multiparous women. ConclusionsPregnancy is a relevant source of HLA antibodies sensitization, but not of AT1R antibodies. HLA antibodies increased clearly in primiparous women with predominance of class II. The use of newer solid-phase techniques on Luminex evidence a higher degree of HLA sensitization during pregnancy.

The Effect of Preformed Anti-Human Leukocyte Antigens Antibodies on Graft and Patient Outcomes in Kidney Transplantation

The Effect of Preformed Anti-Human Leukocyte Antigens Antibodies on Graft and Patient Outcomes in Kidney Transplantation

Difficulties in diagnosing and predicting possible complications in patients after heart transplantation: single-center experience in the Krasnodar region

Aim. To evaluate the early and long-term outcomes of heart transplantation (HT) at the Research Institute of the S. V. Ochapovsky Regional Clinical Hospital № 1.Material and methods. On the basis of the Research Institute of the S. V. Ochapovsky Regional Clinical Hospital № 1 from March 2010 to March 2023, 230 HTs were carried out. Among the patients, men predominated 86% (n=198), women — 14% (n=32). The mean age was 48,3±11,7 years. The reason for HT in 42,6% (n=98) was ischemic cardiomyopathy (ICM), in 40% (n=92) — dilated cardiomyopathy (DCM), while 17,4% were operated on for another cardiac pathology (n=40). All recipients underwent immunological examination, endomyocardial biopsy (EMB), 2D-speckle-tracking echocardiography (2D-STE), transthoracic echocardiography (TTE), coronary angiography (CAG), as well as a number of studies for early diagnosis of possible cancer complications.Results. Acute rejection during the first three years was detected in 77 recipients (42,5%), of which cellular rejection (grade ≥2, 3) and humoral rejection was verified in 49 and 28 recipients, respectively. During the entire follow-up period, de novo anti-human leukocyte antigen (HLA) antibodies were detected in 34 recipients in the posttransplantation period, of which 50% (n=17) and 35% (n=12) were diagnosed with humoral and cellular rejection, respectively. Of the 34 patients with anti-HLA antibodies, 11 (32%) died. All of them died due to a humoral rejection. The survival rate of patients with antibodies was lower (59%) than in patients without antibodies (66%), p=0,023. The annual survival rate of all patients after transplantation in our center was 83,1% (during the first year after transplantation, 30 and 9 patients died due to an acute rejection and infectious complications, respectively).Conclusion. Since the introduction and modification of immunosuppressive therapy regimens, tremendous progress has occurred, and the incidence of acute cellular rejection has decreased. However, the risk of humoral rejection and long-term complications remains one of the main reasons for graft failure.

Clinical significance of late onset antibody-mediated rejection without donor-specific anti-human leukocyte antigen antibodies in kidney transplantation

Clinical significance of late onset antibody-mediated rejection without donor-specific anti-human leukocyte antigen antibodies in kidney transplantation

Pretransplant immunologic risk assessment in high baseline ABO antibody titers and donor-specific anti-human leukocyte antigen antibodies in ABO incompatible kidney transplantation

Pretransplant immunologic risk assessment in high baseline ABO antibody titers and donor-specific anti-human leukocyte antigen antibodies in ABO incompatible kidney transplantation

IgM marks persistent IgG anti-human leukocyte antigen antibodies in highly sensitized heart transplant patients

Sensitization to human leukocyte antigens (HLA) is a persistent problem in heart transplant (HT) candidates. We sought to characterize the anti-HLA antibody and circulating B cell repertoire in a cohort of highly sensitized HT candidates. We assessed IgG and IgM anti-HLA antibodies using luminex single antigen bead assays in a cohort of 11 highly sensitized (HS; calculated panel reactive antibody ≥ 90%) and 3 mildly sensitized (MS) candidates. We also performed B cell receptor repertoire sequencing (BCRseq) in HS candidates and 33 non-candidate controls. HLA antibody strength was measured by mean fluorescence intensity (MFI). We found that IgM anti-HLA antibodies were present in all HS candidates, but with a lower breadth and strength as compared to IgG. When anti-HLA IgG specificities intersected with IgM, binding strength was higher. In contrast, there were IgM but no intersecting IgG specificities for the MS group. In four candidates in the HS group, IgG anti-HLA antibodies decreased in both breadth and strength after HT, but the decrease in strength was smaller if the IgG possessed a specificity that intersected with pre-transplant IgM. BCRseq revealed larger B cell clonotypes in HS candidates but similar diversity as compared to controls. IgM marks IgG anti-HLA antibodies with higher strength before HT and persistence after HT. The presence of IgM intersecting IgG for an anti-HLA specificity may be useful approach to determine which donor HLA should be avoided for a sensitized candidate.

P619 Serum reduction, a cost effective and efficient treatment to reduce non-specific binding in screening for anti-human leukocyte antigen (HLA) antibodies

P619 Serum reduction, a cost effective and efficient treatment to reduce non-specific binding in screening for anti-human leukocyte antigen (HLA) antibodies

TNF-α -308A/G SNP association with kidney allograft rejection in Algerian population: A retrospective case-control study

No consensus has been reached regarding the association beween the -308A/G single nucleotide polymorphism (SNP) in the tumor necrosis factor-α gene (TNFA) and kidney allograft rejection (KAR). Our retrospective case-control study aimed to assess the association of the SNP with KAR in Algerian patients who underwent kidney transplantation. The study enrolled 313 Algerian patients: 58 kidney-transplant recipients without rejection events (PWoR); 58 kidney-transplant recipients with at least one rejection event, with or without graft loss (PWR); and 197 healthy individuals (HI). The TNFA -308A/G SNP was genotyped using a real-time polymerase chain reaction. The results demonstrated that, the frequencies of TNFA -308A allele and AA genotype were higher in the PWR than in the HI groups (p = 0.001, OR = 2.26, CI = 1.33‐3.77 and p = 0.0004, OR = 5.53, CI-1.89-16.6, respectively). Furthermore, the frequencies were higher among the PWR than among the PWoR groups (p = 0.001, OR = 3.29, CI = 1.56‐7.21 and p = 0.0006, OR = 28.26, CI = 1.62‐493.2, respectively), particularly among PWR patients with de novo anti-human leukocyte antigens (HLA) antibodies (PG-a-HLA-Ab). However, the frequency of TNFA -308G allele was lower in the PWR group than in the PWoR group (p = 0.001, OR = 0.3, CI = 0.1‐0.64) and the HI group (p = 0.001, OR = 0.44, CI = 0.27‐0.44). Our results suggest an association of the TNFA -308A/G alleles with KAR in Algerian patients who underwent kidney transplantation. Carriers of TNFA -308A allele who have PG-a-HLA-Ab might have a higher risk, whereas TNFA -308G allele carriers could have a lower risk of KAR. Thus, therapeutic strategies can be adapted to minimize KAR risk in patients who have a genetic proclivity for increased pro-inflammatory TNF-α activity.

Living Donor Liver Transplantation in Patients with Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies Using Preoperative Desensitization Therapy According to Intensity of Donor-Specific Antibodies: A Single-Center Study.

BACKGROUND In liver transplantation (LT), preoperative desensitization therapy is considered necessary in patients positive for donor-specific anti-human leukocyte antigen antibodies (DSAs). However, the relationship between DSA intensity and the necessary desensitization therapy is unclear. MATERIAL AND METHODS A total of 37 adult living donor (LD) LTs performed between January 2016 and March 2022 were examined. Mycophenolate mofetil (MMF) was administered preoperatively in DSA-positive cases with positive lymphocyte cross-matching who underwent LDLT. In those with strongly positive DSA (mean fluorescence intensity 10 000), rituximab was administered 2 weeks before LDLT in addition to MMF. Cross-reactive epitope group antigen (CREG)-alone-positive cases were also treated with preoperative MMF when lymphocyte cross-matching was positive. RESULTS Of the 37 patients, 9 were DSA-positive, 7 were CREG-alone-positive, and the others were double-negative. Of 9 DSA-positive cases, desensitization therapy was performed in 7, among which rituximab administration was performed in 3 strongly DSA-positive cases. Of 7 CREG-alone-positive cases, 2 were lymphocyte cross-match-positive and underwent desensitization therapy. The 1-year survival rate was 100% in both DSA- and CREG-alone-positive cases. The frequency of T-cell mediated rejection in DSA-positive, CREG-alone-positive, and double-negative cases was 22%, 43%, and 29%, respectively, with no significant difference. Antibody-mediated rejection occurred in only 1 patient, who was strongly DSA-positive and blood-group incompatible. There was also no significant difference among the 3 groups in terms of the frequency of biliary complications or 90-day mortality. CONCLUSIONS Satisfactory LDLT results were achieved in DSA- and CREG-alone-positive cases following desensitization therapy.

Dual Antibody Treatment for Simultaneous Acute Cellular Rejection and Antibody-Mediated Rejection After Liver Transplantation: A Case Report

Antibody-mediated rejection (AMR) after liver transplantation is uncommon but sometimes has a grave prognosis. We herein describe a 40-year-old man who developed simultaneous acute cellular rejection and acute AMR due to de novo donor-specific anti-human leukocyte antigen antibodies after living donor liver transplantation. He underwent living donor liver transplantation with his brother-in-law as the donor. Hepatic function deteriorated on postoperative day 6, and a liver biopsy revealed histologic findings of typical acute cellular rejection. However, steroid pulse therapy and thymoglobulin did not produce a clinical response, and his liver function dramatically deteriorated on postoperative day 13 (aspartate aminotransferase, 2787 IU/L; total bilirubin, 14.1 mg/dL). We diagnosed acute AMR based on positive immunohistochemical staining for C4d in portal areas and added plasma exchange and high-dose intravenous immunoglobulin after rituximab. The patient's clinical state improved and ultimately resolved. To our knowledge, this is the first report of dual antibody treatment for simultaneous acute cellular rejection and acute AMR induced by de novo donor-specific anti-human leukocyte antigen antibodies. Despite his fulminant clinical course, we successfully rescued the recipient with immediate anti-humoral therapy. The rapid treatment decision and adequate understanding of the mechanisms of anti-humoral therapy were crucial to overcoming acute AMR in this case.

Heart transplantation and anti-HLA antibodY: myocardial dysfunction and prognosis - HeartLAy study.

The presence of anti-human leucocyte antigen (HLA) antibodies has been implicated in a higher incidence of complications as well as mortality rate in heart transplantation. The aim of the study was to identify through non-invasive parameters early signs of myocardial dysfunction in the presence of anti-HLA antibodies but without evidence of antibody-mediated rejection (AMR) and its possible prognostic impact. A total of 113 heart-transplanted patients without acute cellular rejection (ACR) and AMR or cardiac allograft vasculopathy (CAV) were prospectively enrolled and divided into two groups ['HLA+' (50 patients) and 'HLA-' (63 patients)], based on the presence of anti-HLA antibodies. Each patient was followed for 2years after the enrolment, recording episodes of AMR, ACR, CAV, and mortality. Clinical characteristics were similar between the two groups. Among laboratory data, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin values were significantly higher in the presence of anti-HLA antibodies (P<0.001 and P=0.003, respectively). The echocardiographic parameters that showed a statistically significant difference between the two groups were deceleration time of E wave (DecT E, P<0.001), left ventricular global longitudinal strain (P<0.001), tricuspid annular plane systolic excursion (P=0.011), tricuspid S' wave (P=0.002), and free wall right ventricular longitudinal strain (fwRVLS, P=0.027), whereas left atrial strain did not differ significantly (P=0.408). Univariate analysis showed that anti-HLA antibodies were associated with the development of CAV at both 1 and 2year follow-up [odds ratio (OR) 11.90, 95% confidence interval (CI) 1.43-90.79, P=0.022 and OR 3.37, 95% CI 1.78-9.67, P=0.024, respectively]. Bivariate analysis demonstrated that both fwRVLS and DecT E were predictors of CAV development independently from HLA status. The presence of circulating anti-HLA antibodies is correlated with a mild cardiac dysfunction, even in the absence of AMR, and CAV development. Interestingly, reduced values of DecT E and fwRVLS were predictors of future development of CAV, independently from anti-HLA antibody.

[Discussion on two common problems in renal transplantation donor-specificity discrimination of anti-human leukocyte antigen antibody].

Antibody-mediated rejection (AMR) is a key factor affecting the long-term survival of renal allografts. Donor-specific antibody (DSA) is the etiology of AMR. So it is very important to accurately detect DSA. The single antigen bead (SAB) method, which is widely used in clinical practice, is prone to miss DSA detection and underestimate its mean fluorescence intensity (MFI). In this paper, the probability of missed detection of two SAB reagents was calculated by comparing common HLA alleles in China population, and the in vitro effect of antibody cross reaction on MFI value of DSA was revealed. The authors emphasized the clinical significance of the above two problems, tried to manage them by using functional epitope (eplet) analysis and give some clinical examples. Finally, the limitations of this correction method were analyzed.

Lung transplantation despite preformed donor-specific antihuman leukocyte antigen antibodies: a 9-year single-center experience

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient’s waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P = .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P = .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients.

MP31-17 LOW-DOSE RITUXIMAB INDUCTION THERAPY IN IMMUNOLOGIC HIGH-RISK RENAL TRANSPLANTATION PROVIDES FAVORABLE GRAFT OUTCOMES WITHOUT INCREASING CYTOMEGALOVIRUS INFECTION: A 5-YEAR FOLLOW-UP

You have accessJournal of UrologyCME1 Apr 2023MP31-17 LOW-DOSE RITUXIMAB INDUCTION THERAPY IN IMMUNOLOGIC HIGH-RISK RENAL TRANSPLANTATION PROVIDES FAVORABLE GRAFT OUTCOMES WITHOUT INCREASING CYTOMEGALOVIRUS INFECTION: A 5-YEAR FOLLOW-UP Kasumi Yoshinaga, Yuki Maruyama, Tomoaki Yamanoi, Shingo Nishimura, Yusuke Tominaga, Satoshi Katayama, Takehiro Iwata, Kohei Edamura, Tomoko Kobayashi, Yasuyuki Kobayashi, Toyohiko Watanabe, and Motoo Araki Kasumi YoshinagaKasumi Yoshinaga More articles by this author , Yuki MaruyamaYuki Maruyama More articles by this author , Tomoaki YamanoiTomoaki Yamanoi More articles by this author , Shingo NishimuraShingo Nishimura More articles by this author , Yusuke TominagaYusuke Tominaga More articles by this author , Satoshi KatayamaSatoshi Katayama More articles by this author , Takehiro IwataTakehiro Iwata More articles by this author , Kohei EdamuraKohei Edamura More articles by this author , Tomoko KobayashiTomoko Kobayashi More articles by this author , Yasuyuki KobayashiYasuyuki Kobayashi More articles by this author , Toyohiko WatanabeToyohiko Watanabe More articles by this author , and Motoo ArakiMotoo Araki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003264.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We previously reported that low-dose rituximab induction therapy in immunologic high-risk patients for living donor renal transplantation did not increase CMV infections when preemptive therapy was performed. We now report additional long-term outcomes. METHODS: One-hundred thirty-one recipients undergoing living-donor renal transplantation in our institution from May 2009 to September 2021 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: 1. ABO major mismatch, 2. ABO minor mismatch, 3. donor-specific anti-human leukocyte antigen antibody (DSA)-positive, 4. Focal segmental glomerulosclerosis (FSGS). RESULTS: There were 83 patients in the rituximab group and 34 in the non-rituximab group. Groups differed significantly in age (median age, 51 vs 42 years, respectively; P=0.03), but not in sex (male, 66% vs 68% P=1.00), FSGS (4% vs 0%, P=0.56). Estimated glomerular filtration rate did not differ significantly between groups until 5 years after transplantation (Figure 1). CMV clinical symptoms (14% vs 26%, P=0.18), including fever over 38 degrees (8% vs 12%, P=0.73) and gastrointestinal symptoms (7% vs 12%, P=0.06), and the 5-year survival rates of death-censored graft loss (95% vs 96%, P=0.52) did not differ significantly between two groups (Figure 2). CONCLUSIONS: As in our previous study, low-dose rituximab induction therapy was effective in immunologically high-risk recipients without increasing CMV infection without valganciclovir prophylaxis. Furthermore, the graft survival rate and renal function at 5 years after transplantation were equivalent to those in the non-rituximab group. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e436 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kasumi Yoshinaga More articles by this author Yuki Maruyama More articles by this author Tomoaki Yamanoi More articles by this author Shingo Nishimura More articles by this author Yusuke Tominaga More articles by this author Satoshi Katayama More articles by this author Takehiro Iwata More articles by this author Kohei Edamura More articles by this author Tomoko Kobayashi More articles by this author Yasuyuki Kobayashi More articles by this author Toyohiko Watanabe More articles by this author Motoo Araki More articles by this author Expand All Advertisement PDF downloadLoading ...

Anti-human leukocyte antigen and anti-ABO antibodies after SARS-CoV-2 mRNA vaccination in kidney transplant recipients.

In this study, we evaluated whether SARS-CoV-2 mRNA vaccines induce anti-human leukocyte antigen (HLA) antibodies and anti- ABO blood type antibodies (ABOAb) in kidney transplant recipients (KTRs). Sixty-three adult KTRs with functioning grafts who received two doses of the SARS-CoV-2 mRNA vaccine were enrolled in this cohort. Changes in anti-ABO blood type immunoglobulin IgM and IgG antibody titers, flow panel reactive antibody (PRA), de novo donor-specific anti-human leukocyte antigen antibodies (DSA), and kidney allograft function before and after vaccination were evaluated. Only one patient experienced conversion from negative to positive flow PRA after vaccination. However, there was no DSA in single antigen flow-bead assays. The mean fluorescence intensity (MFI) in the eight DSA-positive recipients did not significantly change before and after vaccination (p=.383), and no additional DSA was produced after vaccination in those patients. No significant elevation of ABOAb titer was observed for either IgM (p=.438) or IgG (p=.526) after vaccination. There was no significant deterioration in estimated glomerular filtration rate (eGFR) after vaccination (p=.877) or elevation of the urine protein-to-creatinine ratio (p=.209) after vaccination. One episode of AMR was observed in addition to a preexisting acute cellular rejection. The SARS-CoV-2 mRNA vaccine did not induce anti-HLA antibody or ABOAb production in KTRs.

Human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes are important in transplant immunology in the liver

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance, which is described by eventual imbalances or deregulation in the balance of cytokines, mediators, effectors, and regulatory cells in the complex milieu of the liver. In this section, we will comment on the importance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor (KIR) genotypes in the evolution of liver transplantation. Thus, HLA compatibility, viral infections, and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival. There have been reports of increased risk of acute and chronic rejection with ductopenia, faster graft fibrosis, biliary problems, poorer survival, and even de novo autoimmune hepatitis when DSAs are present in the recipient. Higher mean fluorescence intensity (MFI) values of the DSAs and smaller graft size were associated with poorer patient outcomes, implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods, according to the investigators. Similarly, in a combined kidney-liver transplant, a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment. The renal graft was lost owing to antibody-mediated rejection (AMR). The HLA antigens expressed by the transplanted liver graft influenced antibody elimination. Pathologists are increasingly diagnosing AMR in liver transplants, and desensitization therapy has even been employed in situations of AMR, particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex. In conclusion, after revealing the negative impacts of DSAs with high MFI, pretransplant virtual crossmatch techniques may be appropriate to improve evolution; however, they may extend cold ischemia periods by requiring the donor to be typed.