The Association Between Hla-B40, Hla-Dqa1*01 and Hla-Dqb1*05 Alleles and Antibody Response to Hepatitis B Vaccination in Turquish Hemodislysis Patients / Asociación entre los Alelos Hla-B40, Hla-Dqa1*01 y Hla-Dqb1*05 y Respuesta de Anticuerpos a la Vacuna contra la Hepatitis B en Pacientes Turcos en Hemodiálisis

Abstract Introduction: Hepatitis B virus (HepB) infection is a global health problem with increasing cause of morbidity and mortality.Hemodialysis patients are especially vulnerable to HepB infection due to uremia-related immune dysfunction, frequent interventions they exposed, and health-care personnel's unsafe care. The vaccination against HepB confers the primary preventive measure. However, unresponsiveness to vaccination constitutes a major problem. Several factors can influence the immune response to vaccines but human genetic variations are thought to strongly militate the variability in vaccine responsiveness. We aimed to determine the association with specific HLA alleles and response to HepB vaccination in hemodialysis patients. Methods: The study included in-center hemodialysis patients. We retrospectively collected data regarding demographic, clinical, and laboratory features including anti-HBs antibody, antibody to hepatitis C (anti-HCV), anti-HIV, and specific HLA class I and II alleles (HLA-A, HLB, HLA-DR) from electronical medical record system. The frequencies of HLA class I and II antigens in nonresponders and responders were analyzed. Results: The most commonly observed HLA alleles in patients were DQA1*01 (%73.7), DQA1*05 (%57.9), DQB1*03 (%53.8), DQB1*05 (%38.5), and DRB1*11 (%37.3), respectively. The frequency of HLA-B40 allel was significantly higher in nonresponders (p=0.02, OR=6.25, 95%CI =1.33-29.3). HLA-DQA1*01 and HLA-DQB1*05 alleles were observed significantly more in responders (p=0.019, OR =6.9, 95% CI=1.40-33.91, andp=0.028, OR =10, 95% CI=1.12-88.91, respectively). Conclusion: This is the first study to our knowledge demonstratingthe association between antibody response to HBsAg and HLA-B40, HLA-DQA1*01, and HLA-DQB1*05 alleles in Turkish hemodialysis patients.

Resumen Introducción: La infección por el virus de la hepatitis b (VHB) constituye un problema de salud mundial con una morbimortalidad cada vez mayor.Los pacientes que reciben hemodiálisis están particularmente expuestos a una infección por el virus de la hepatitis b debido a una disfunción del sistema inmunitario relacionada con la uremia, las intervenciones a las que se someten frecuentemente y prácticas poco seguras por parte del personal de salud. La vacuna contra el VHB constituye la medida preventiva principal. Sin embargo, la falta de respuesta a la vacuna supone un gran problema. Existen varios factores que pueden influir sobre la respuesta inmunitaria a la vacuna, pero se cree que las variaciones genéticas humanas tienen una gran incidencia sobre la variación en la respuesta a la vacuna. El objetivo de este trabajo fue determinar la relación entre alelos HLA específicos y la respuesta a la vacuna contra el VHB en pacientes que reciben hemodiálisis. Material y métodos: El estudio incluyó pacientes en hemodiálisis hospitalaria. Se recopilaron datos retrospectivamente del sistema electrónico de registros médicos sobre características demográficas, clínicas y de laboratorio, incluidos anticuerpos anti-HBs, anticuerpos contra la hepatitis C (anti-VHC), anti-VIH y alelos HLA específicos de clase I y II (HLA-A, HLA-B, HLA-DR). Se analizaron las frecuencias de los antígenos HLA clase I y II en pacientes que no respondían y en aquellos que sí lo hacían. Resultados: Los alelos HLA más comúnmente observados en pacientes fueron DQA1 * 01 (73,7%); DQA1 * 05 (57,9%); DQB1 * 03 (53,8%); DQB1 * 05 (38,5%), y DRB1 * 11 (37.3%), respectivamente. La frecuencia del alelo HLA-B40 fue significativamente mayor en los que no respondieron (p=0,02; OR = 6,25; IC 95% = 1,33-29,3). Se observó que los alelos HLA-DQA1*01 y HLA-DQB1*05 aparecían mayormente en los pacientes que respomdían (p=0,019; OR = 6,9; IC 95% = 1,40-33,91, y p=0,028; OR=10; IC 95% = 1,12- 88,91, respectivamente). Conclusión: Este es el primer estudio que conocemos que demuestra la asociación entre la respuesta de anticuerpos a HBsAg y a alelos HLA-B40, HLA-DQA1*01 y HLA-DQB1*05 en pacientes turcos en hemodiálisis.

De novo produced anti-human leukocyte antigen antibodies relation to alloimmunity in patients with chronic renal failure.

AIMS: Chronic renal failure causes patients to become dialysis dependent, which is exhausting for them both financially and psychologically. However, the definitive treatment of chronic renal failure is transplantation. One of the crucial factors affecting success in transplantation is the presence of anti-human leukocyte antigen (HLA) antibodies in patients. HLA alloimmunization is caused by various sensitization events such as blood transfusion, pregnancy, and transplantation. In this study, different sensitization events were compared to determine the effectiveness on the panel-reactive antibody status in female solid organ transplantation candidates based upon pregnancy. RESULTS: When results were evaluated in terms of alloimmunization rates, 62.8%, 73.4%, and 14.9% of the patients were found to have blood transfusion, pregnancy, and rejection history, respectively. Three hundred twenty-six of the 444 women had had at least one pregnancy. Panel-reactive antibody (PRA) (class I and/or II)-positive rates were significantly higher among patients with pregnancy and blood transfusion history (43.7%) than patients with only pregnancy history (27.5%) and pregnancy and transplantation history (40%). While transplantation history significantly affects class II anti-HLA levels, blood transfusion raises class I levels. CONCLUSIONS: Solid organ transplantation appears to have the strongest HLA alloimmunization effect followed by pregnancy and blood transfusion, especially for class II HLA antigens. Patients who were sensitized by more than one sensitization event have a lower chance to have a solid organ transplantation. In this case, identification of donor-specific antibodies and the results of the cross-match tests play an important role both before and postrenal transplantation.

Effect of cyclosporin A and tacrolimus on sister chromatid exchange frequency in renal transplant patients.

Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients.