Türk Fanconi anemili hastalarda HLA alellerinin sıklığı ve ilişkisi

Yıl 2024, Cilt: 49 Sayı: 3, 607 - 613, 30.09.2024

Behnoush Nasr Zanjani , Hayriye Şentürk Çiftçi , Çiğdem Kekik Çınar , Tülin Tiraje Celkan , Nevin Yalman , Fatma Savran Oğuz

https://doi.org/10.17826/cumj.1443687

Öz

Amaç: Fanconi anemisi (FA), kemik iliği yetmezliği, çeşitli konjenital fiziksel anomaliler, kansere yatkınlık, kromozomal instabilite ve çapraz bağlayıcı ajanlara karşı aşırı duyarlılık ile karakterize otozomal resesif geçişli bir çocukluk çağı hastalığıdır. Bu çalışmanın amacı, Türk hastalarda HLA Sınıf I ve Sınıf II alellerinin Fanconi anemisine genetik yatkınlıktaki rolünü belirlemektir.
Gereç ve Yöntem: Bu çalışmada, 2010-2021 yılları arasında hematopoietik kök hücre nakli gerçekleşen Fanconi anemisi hastalarının HLA-A, -B, -DRB1 alel frekanslarını retrospektif olarak değerlendirdik. Tüm hastalara HLA tiplemesi yapıldı ve ayrıca sağlıklı Türk bireylerde de alelleri genotiplendirdik.
Bulgular: Çalışmaya 86 Fanconi anemili hasta ve 300 sağlıklı control dahil edilmiştir. Fanconi hastalarında en yaygın antijenler HLA-A*02, HLA-B*35 ve DRB1*11 idi. Ayrıca, hasta grubunda HLA-A*23 aleli kontrol grubuna göre anlamlı derecede düşüktü. Hasta grubunu cinsiyete göre değerlendirdiğimizde, HLA-A*01 aleli kadın hasta grubunda anlamlı olarak daha yüksekti.
Sonuç: Çalışmamız, HLA Sınıf I ve Sınıf II alellerinin rolüne odaklanarak, türk hastalarda Fanconi anemisi'nin genetik duyarlılığı hakkında değerli öngörüler sunmaktadır. HLA-B*14, Fanconi anemisi için bir risk faktörü olabilirken, HLA-A*23 koruyucu olabilir. Bu sonuçlar, Fanconi anemisi'nin karmaşık genetik faktörlerini anlamamıza katkıda bulunmakla beraber, etkilenen bireyler için daha iyi teşhis, prognoz ve potansiyel tedavi müdahaleleri açısından önemli olabilir.

Anahtar Kelimeler

Fanconi anemisi, HLA, genotipleme, homozigotluk

Etik Beyan

The study protocol was approved by the ethical committee of Istanbul Faculty Medicine (No: 2021/38)

Frequency and relationship of HLA allele in Turkish patients with Fanconi anemia

Öz

Purpose: Fanconi anemia (FA) is a childhood disorder inherited in an autosomal recessive manner. It is characterized by bone marrow failure, a range of congenital physical abnormalities, increased susceptibility to cancer, chromosomal instability, and heightened sensitivity to cross-linking agents. The aim of this study was to determine the role of the HLA Class I and Class II alleles in genetic susceptibility to Fanconi anemia in Turkish patients.
Materials and Methods: In this study, we retrospectively evaluated the HLA-A, -B, and -DRB1 allele frequencies of patients with Fanconi anemia who underwent hematopoietic stem cell transplantation between 2010 and 2021. HLA-A, -B, -DR of all patients and healthy Turkish individuals were genotyped.
Results: The study included 86 patients with Fanconi anemia and 300 healthy controls. The most common antigens in patients with Fanconi were HLA-A*02, HLA-B*35 and DRB1*11. Moreover, in the patient group, the HLA-A*23 allele was significantly lower than the control group. When we evaluated the patient group according to gender the HLA-A*01 allele was significantly higher in the female patient group.
Conclusion: Our study provides valuable insights into the genetic susceptibility of Turkish patients with Fanconi anemia, focusing on the role of HLA Class I and Class II alleles. HLA-B*14 may be a risk factor and HLA-A*23 may be protective for Fanconi anemia. These results contribute to our understanding of the complex genetic factors underlying Fanconi anemia and may have implications for improved diagnosis, prognosis, and potential therapeutic interventions for affected individuals.

Anahtar Kelimeler

Fanconi anemia, HLA, genotyping, homozygosity

Kaynakça

• Che R, Zhang J, Nepal M, Han B, Fei P. Multifaceted Fanconi anemia signaling. Trends Genet. 2018;34:171-83.
• Peake, J.D., Noguchi, E. Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair. Hum Genet 2022;141, 1811–36.
• Gueiderikh A, Rosselli F, Neto JBC. A never-ending story: the steadily growing family of the FA and FA-like genes. Genet Mol Biol. 2017;40:398-407.
• Kottemann MC, Smogorzewska A. Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature. 2013;493:356-63.
• Bhattacharjee S, Nandi S. DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway. Cell Commun Signal. 2017;15:41.
• Kee Y, D’Andrea AD. Molecular pathogenesis and clinical management of Fanconi anemia. J Clin Invest. 2012;122:3799-806.
• Cancio, M., Troullioud Lucas, A.G., Bierings, M. Klein E, Witte MA., Smiers FJ et al. Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia. Bone Marrow Transplant. 2024;59, 34–40.
• Ebens CL, MacMillan ML, Wagner JE. Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations. Expert Rev Hematol. 2017;10:81-97.
• Dendrou CA, Petersen J, Rossjohn J, Fugger L. HLA variation and disease. Nat Rev Immunol. 2018;18:325-39.
• Angaswamy N, Tiriveedhi V, Sarma NJ, Subramanian V, Klein C, Wellen J et al. Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection. Hum Immunol. 2013;74:1478-85.
• Akıllı R, Emre C, Kaypaklı CO, Kanadaşı M, Demirtaş M. New genetic risk factors for myocardial infarction at young patients in southern Turkey. Cukurova Medical Journal. 2020;45:1-8.
• Agarwal RK, Kumari A, Sedai A, Parmar L, Dhanya R, Faulkner L. The case for high resolution extended 6-loci HLA typing for identifying related donors in the Indian subcontinent. Biol Blood Marrow Transplant. 2017;23:1592-6.
• Wagner JE, Eapen M, MacMillan ML, Harris RE, Pasquini R, Boulad F et al. Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia. Blood. 2007;109:2256-62.
• Gluckman E, Rocha V, Ionescu I, Bierings M, Harris RE, Wagner J et al. Results of unrelated cord blood transplant in fanconi anemia patients: risk factor analysis for engraftment and survival. Biol Blood Marrow Transplant. 2007;13:1073-82.
• Naranbhai V, Viard M, Dean M, Groha S, Braun DA, Labaki C et al. HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study. Lancet Oncol. 2022;23:172-84.
• Dausset J, Gluckman E, Lemarchand F, Nunez-Roldan A, Contu L, Hors J et al. Excess of HLA-A2 and HLA-A2 homozygotes in patients with aplastic and Fanconi's anemias. Nouv Rev Fr Hematol Blood Cells.. 1977;18:315-24.
• Sayad A, Dehaghi MO, Taheri M, Fallah H, Arsang-Jang S, Shadnoush M et al. Identification of HLA-A/B/DRB1 alleles in Iranian patients with Fanconi anemia. Hum Antibodies. 2020;28:221-6.
• Grewal SS, Kahn JP, MacMillan ML, Ramsay NK, Wagner JE. Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype–identical sibling selected using preimplantation genetic diagnosis. Blood. 2004;103:1147-51.
• Fu RT, Xue HM, Zhang BH, Wang J, Lin SF, Chen C et al. Correlation analysis of severe aplastic anemia immunosuppressive therapy and human leukocyte antigen alleles in pediatric patients. Exp Ther Med. 2015; 10:2396-402