MHC Class II Deficiency: Clinical, Immunological, and Genetic Insights in a Large Multicenter Cohort
Makaleler > Tam Makale · 2024
Yazarlar: Zeynep Gulec Koksal, Sevgi Bilgic Eltan, Ezgi TOPYILDIZ, Ahmet Sezer, Sevgi Keles, Figen Celebi Celik, Aylin Ozhan Kont, Betul Gemici Karaaslan, Asena Pinar Sefer, Zuhal Karali, Elif Arik, Esra Ozek Yucel, Omer Akcal, Leman Tuba Karakurt, Melek Yorgun Altunbas, Koray Yalcin, Koray Yalcin, Vedat Uygun, Gülcihan ÖZEK, Royala Babayeva, Cigdem Aydogmus, Dilek Ozcan, Ozlem Cavkaytar, Ozlem Keskin, Sara Sebnem Kilic, Ayca Kiykim, Tugba Arikoglu, Ferah Genel, Nesrin Gulez, Sukru Nail Guner, Neslihan KARACA, Ismail Reisli, Necil KÜTÜKÇÜLER, Derya Ufuk Altintas, Ahmet Ozen, Elif Karakoc Aydiner, Safa Baris
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, SCI Expanded İndekslerine Giren Dergi, Uluslararası, IM: Index Medicus , 2024, cilt 12, ss 2490-2502.e6
DOI: 10.1016/j.jaip.2024.06.046
Özet
Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored. Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates. Methods: In this multicenter retrospective analysis, we gathered data from 35 patients with a diagnosis of MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes. Results: Predominant symptoms observed were pneumonia (n = 29; 82.9%), persistent diarrhea (n = 26; 74.3%), and severe infections (n = 26; 74.3%). The RFXANK gene mutation (n = 9) was the most frequent, followed by mutations in RFX5 (n = 8), CIITA (n = 4), and RFXAP (n = 2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared with those with RFX5 mutations (P =.0008 and .0006, respectively), alongside a more significant diagnostic delay (P = .020). A notable founder effect was observed in five patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n = 10), showing a significantly higher proportion in individuals with hematopoietic stem cell transplantation (n = 8; 80%). Early death and higher CD8+ T-cell counts were observed in patients with the RFX5 mutations compared with RFXANK-mutant patients (P = .006 and .009, respectively). Conclusions: This study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency.