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.

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.

Association between panel reactive antibody and antiendothelial cell antibody positivity in kidney transplant patients.

OBJECTIVES: Endothelium is the major tissue for hyperacute and acute rejection. Binding of antibody to endothelium activates several immunologic mechanisms. Antiendothelial cell antibodies are a group of nonhuman leukocyte antigen antibodies that may play a role in the induction of an immunologic reaction that triggers inflammation. The aim of this study was to investigate whether there was an association between antiendothelial cell antibody positivity and panel reactive antibody positivity in renal transplant patients. MATERIALS AND METHODS: In this study, we investigated the association between antiendothelial cell antibodies and panel reactive antibody Class I class II crossmatch positivity in patients, and compared these results with results from 100 healthy volunteers. All serum samples were analyzed by bead-based technology for calculated panel reactive antibody positivity; in addition, slides were used, each containing human umbilical vein endothelial cells and capillary-rich tissue for antiendothelial cell antibody positivity. RESULTS: Antiendothelial cell antibodies was positive in 48 of 89 patients (panel reactive antibody Class I class II negative), 22 of 35 patients (class I-positive), 25 of 39 patients (class II-positive), 26 of 40 (class I class II positive), and 37 of 57 serologic and flow cytometry crossmatch-positive patients (P ≤ .016), and ultimately, in 122 of 205 patients and 25 of 100 volunteers (P ≤ .001). Antiendothelial cell antibody positivity was more frequent in panel reactive antibody-positive than negative patients and the control group. CONCLUSIONS: Binding of antiendothelial cell antibodies to endothelial cells may activate complement by the classical pathway and cause upregulation of adhesion molecules. This study questioned the antigenic specificity of antiendothelial cell antibodies. Our study results showed that antiendothelial cell antibodies may play an important role for graft destruction, independent of panel reactive antibody and crossmatch positivity.