HLA-B*51 Frequency in Transplant Patients and Donors.

OBJECTIVES: HLA molecules play a crucial role in transplantation. The best treatment modality in patients with end-stage renal disease is renal transplant. HLA mismatches between patients and donors can prolong time for renal transplant therapy, reduce graft survival, and increase mortality. HLA region is the most polymorphic genetic region and is essential for antigen presentation. The main target of the recipient's immune system is HLA molecules on the surface of donor cells. HLA-B*51 is associated with Behcet disease, a rare multisystemic disease characterized by autoimmunity and inflammatory processes. In transplant recipients, inflammation and vasculitis are immunologic mechanisms that are responsible for damage of graft tissue. In this retrospective study, we aimed to investigate the frequency of HLA-B*51 in patients diagnosed with end-stage renal disease and in controls and to investigate correlations with rejection episodes. MATERIALS AND METHODS: Patients who applied to Baskent University Adana Dr. Turgut Noyan Research and Medical Center (between 2010 and 2022) with end-stage renal disease (n = 1732) and a control group (n = 5277) received HLA typing for class I (HLA-A, HLA-B). Sequence-specific primers or sequencespecific oligonucleotides were used. Among patients diagnosed with end-stage renal disease, 321 had kidney transplant. RESULTS: Frequency of HLA-B*51 was 25.92% in patients and 25.22% in controls. No significant differences were found between patients and controls in the frequency of HLA-B*51. Among kidney transplant recipients with HLA-B*51 (n = 72), 38.89% had rejection episodes and 61.11% had no rejection. No significant association was found between HLA-B*51 allele positivity and rejection. CONCLUSIONS: No significant relationship was shown between patients diagnosed with end-stage renal disease and HLA-B*51 positivity. Previous studies support frequency of the HLA-B*51 allele in the control group. Although Behçet disease is known to cause renal vasculitis, HLA-B*51 positivity alone was not associated with vasculitis or inflammation.

Relationship Between Angiotensin II Type 1 Receptor Antibody Positivity and Cytokine Gene Polymorphism in Renal Transplant Patients When Organ Rejection Occurs.

OBJECTIVES: Kidney transplant remains the gold standard for the treatment of end-stage renal disease. Relationships between the presence of non-HLA antibodies, antibodies to AT1R, and cytokine gene polymorphisms with rejection have recently been shown. We sought to determine whether the presence of antibodies to AT1R and cytokine gene polymorphisms affected the development of rejection in pediatric and adult patients, whether a relationship is present between cytokine polymorphism and level of antibodies to AT1R, and whether their presence can be a biomarker pretransplant. MATERIALS AND METHODS: Our study included 100 pediatric and adult kidney transplant patients plus 50 healthy controls. Levels of AT1R antibodies (by enzyme-linked immunosorbent assay) and gene polymorphisms of the cytokines transforming growth factor ß, tumor necrosis factor α, interleukins 6 and 10, and interferon gamma cytokines (by sequence- specific primer-polymerase chain reaction) were studied retrospectively and evaluated with the SPSS statistical program. RESULTS: We found no statistically significant relationship between levels of antibodies to AT1R and gene polymorphisms among the studied cytokines in patients with rejection compared with the healthy controls and patients with uneventful courses posttransplant. However, higher levels of antibodies to AT1R were observed in pediatric compared with adult transplant recipients (P < .001). A statistically significant relationship was also observed between transforming growth factor ß1 C/C G/C low-release and interleukin 6 G/C high-release gene polymorphism and levels of antibodies to AT1R (P < .001). CONCLUSIONS: Because we observed that some gene polymorphisms among the studied cytokines may affect AT1R antibody levels, future studies are needed to understand the mechanism of the relationship. In addition, studies with larger groups are required to sufficiently confirm that higher antibody levels are present in pediatric versus adult patients.

Determination of Cytokine Gene Polymorphisms in a Heart Transplant Patient Resistant to Desensitization Therapy: Case Report.

Heart transplant is the best treatment option for end-stage heart failure. The major goals in solid-organ transplant are organ survivability and functionality. The effects of anti-HLA antibodies and cytokines are important for immune response. Cytokine gene polymorphisms are also effective during cytokine release. Here, we report a heart transplant recipient who was diagnosed with antibody-mediated rejection posttransplant and had an antibody response resistant to desensitization therapy. After transplant, panel reactive antibody screening and identification class I and II tests and Luminex single antigen class I and II tests were performed. Desensitization treatment included intravenous immunoglobulin, plasmapheresis, rituximab, and bortezomib. Because of these reasons, cytokine gene polymorphism tests (consistent with low, intermediate, and high expression levels for tumor necrosis factor α, transforming growth factor ß1, interleukin 6 and 10, and interferon γ) were conducted. We found polymorphic regions compatible with the high-release, proinflammatory action of tumor necrosis factor α and interleukin 6, which induced inflammation and B-cell activation, and polymorphic regions compatible with the intermediate release of the potent immunosuppressive effects of transforming growth factor ß1 and interleukin 10, suggesting that the patient may not be able to effectively suppress the activation of the immune system. The influence of cytokine gene polymorphism on the formation of a resistant antibody response in a patient, despite desensitization, contributed to the proinflammatory response in which these cytokines were involved.

Investigation of the Relationship Between BK Virus and Human Leukocyte Antigens in Kidney Transplant Recipients.

OBJECTIVES: The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been found to be related to HLA molecules. In renal transplant, the main target of the recipient's immune system is the HLA molecules on the surface of donor cells. HLA also plays a role in the development of an immune response to viral infections. After renal transplant, BK virus infections may occur due to immunosuppression. Here, we investigated the relationship between HLA and BK virus in renal transplant recipients. MATERIALS AND METHODS: This retrospective study investigated HLA-A, HLA-B, and HLA-DR tissue typing before renal transplant. DNA was isolated from whole blood, and tissue typing tests were performed based on polymerase chain reaction. Patients were tested for BK virus posttransplant using DNA isolated from urine and/or plasma samples. RESULTS: We found HLA-B*13 allele to be a protective factor (P < .049; odds ratio: 0.131; 95% confidence interval, 0.017-1.029) and HLA-DRB1*03 allele to be a possible risk factor (P < .029; odds ratio: 2.521; 95% confidence interval, 1.157-5.490) against BK virus. No significant relationships were found between BK virus and age, sex, donor type, and HLA mismatch. CONCLUSIONS: HLA class I molecules are known to be effective against viruses with the help of cytotoxic T cells. HLA-B*13 alleles within the HLA class I molecules were identified as protective factors against BK virus. HLA class II is associated with CD4-positive T cells that help secrete immune system cytokines, playing a role in stimulating and suppressing the immune system. We demonstrated that HLA-DRB1*03 allele could be a risk factor against BK virus. This allele may be associated with immunomodulatory cytokine secretion of the immune system.

Anti-HLA Antibody Levels Are Associated With the Risk of Graft Failure After Allogeneic Hematopoietic Stem Cell Transplant.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant provides a curative treatment for a considerable amount of hematologic diseases, and it is widely used today. Successful allogeneic stem cell transplant can be compromised by treatment-related toxicity, graft-versus-host disease, infectious complications, disease relapse, and graft failure. Primary graft failure is an important cause of hematopoietic stem cell transplant failure. Primary graft failure correlates with the level of complement-binding, donor-specific anti-HLA antibodies prior to transplant. MATERIALS AND METHODS: We evaluated 15 patients who underwent hematopoietic stem cell transplant using peripheral blood stem cells in terms of graft failure and anti-HLA antibody levels before transplant. All were treated between January 2015 and June 2016. Pretreatment serum anti-HLA class I and anti-HLA class II antibody levels were measured in all patients. RESULTS: Anti-HLA class I antibodies were present in 7 patients (46.6%) and anti-HLA class II antibodies in 8 (53.3%). All three patients who developed primary graft failure were anti-HLA-positive. CONCLUSIONS: Anti-HLA antibodies are a significant cause of graft failure. It is a situation that must be understood with caution. Our results support the considerations that allogeneic hematopoietic stem cell transplant, especially when a fully compatible sibling donor is not present, should include screening of donor-specific antibodies of alternative donors and desensitization therapy for allosensitized patients before transplant.

The Most Common HLA Alleles and Anti-HLA Antibodies to Know for Virtual Cross-Match.

OBJECTIVES: Human leukocyte antigens and HLAspecific antibodies are important before and after transplant treatment. The determination of the alloantibodies before transplant is useful for the estimation of risk for antibody-mediated rejection. Virtual crossmatch uses solid-phase assay to detect anti-HLA antibodies and allows exclusion of donors with unacceptable HLA antigens. The aim of our retrospective study was to investigate HLA class I and class II alleles and panel reactive antibody and Luminex Corporation (Austin, TX, USA) single-antigen bead assay positivity frequencies in the Southeastern region of Turkey. MATERIAL AND METHODS: Tissue typing results for HLA class I (HLA-A, HLA-B, HLA-C) and class-II (DRB1and DQB1 haplotypes) in 1756 patients and 2951 donors who were at Baskent University Adana Research and Medical Center between 2010 and 2015 for transplant were studied using sequence-specific primers and/or sequence-specific oligonucleotides. Serum samples were analyzed by Luminex bead technology for antibody detection. RESULTS: We found that, for class I, HLA-A*02,HLA-B*35, and HLA-A*24 and, for class II, DRB*11, DRB*01, and DRB*04 were the 4 most common antigens and HLAA02, B49, A68, B7 were the 3 most common anti-HLA antibodies, with mean fluorescence intensity values ≥ 2000 in our population group. Human leukocyte antigen alleles and anti-HLA antibodies were compared with each other except HLA-A*02, A2, with no correlations between allele and panel reactive antibody frequencies identified. However, there was a weak correlation between panel reactive antibodymean fluorescence intensity scores of 5000 and above with Luminex single-antigen bead assay. CONCLUSIONS: This study is the first to conduct such a mass screening of a Turkish population. Our study results show that there is no correlation between HLA frequencies and anti-HLA antibody frequencies. However, there was a weak correlation between panel reactive antibody mean fluorescence intensity scores of 5000 and above with Luminex single-antigen bead assay. Of note, this pattern is important to know for virtual cross-match.