MHC class II deficiency: Clinical, immunological, and genetic insights in a large multicenter cohort.

CD4(+) T lymphocytopenia Combined immunodeficiency MHC-II deficiency clinical outcomes hematopoietic stem cell transplantation

Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
10 Jul 2024
Historique:
received: 08 04 2024
revised: 13 06 2024
accepted: 30 06 2024
medline: 13 7 2024
pubmed: 13 7 2024
entrez: 12 7 2024
Statut: aheadofprint

Résumé

Major Histocompatibility Complex Class II (MHC-II) deficiency, a combined immunodeficiency, results from loss of Human Leukocyte Antigen class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation (HSCT) stands as the sole curative approach, though factors influencing patient outcomes remain insufficiently explored. Our aim was to elucidate the clinical, immunological, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates. In this multicenter retrospective analysis, we gathered data from 35 patients diagnosed with 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. 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 to those with RFX5 mutations (p=0.0008 and p=0.0006, respectively), alongside a more significant diagnostic delay (p=0.020). A notable founder effect was observed in 5 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 HSCT (n=8, 80%). Early demise (p=0.006) and higher CD8 The 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.

Sections du résumé

BACKGROUND BACKGROUND
Major Histocompatibility Complex Class II (MHC-II) deficiency, a combined immunodeficiency, results from loss of Human Leukocyte Antigen class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation (HSCT) stands as the sole curative approach, though factors influencing patient outcomes remain insufficiently explored.
OBJECTIVE OBJECTIVE
Our aim was to elucidate the clinical, immunological, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates.
METHODS METHODS
In this multicenter retrospective analysis, we gathered data from 35 patients diagnosed with 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 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 to those with RFX5 mutations (p=0.0008 and p=0.0006, respectively), alongside a more significant diagnostic delay (p=0.020). A notable founder effect was observed in 5 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 HSCT (n=8, 80%). Early demise (p=0.006) and higher CD8
CONCLUSION CONCLUSIONS
The 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.

Identifiants

pubmed: 38996837
pii: S2213-2198(24)00688-3
doi: 10.1016/j.jaip.2024.06.046
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Zeynep Gulec Koksal (ZG)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey; Department of Pediatric Allergy and Immunology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.

Sevgi Bilgic Eltan (SB)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Ezgi Topyildiz (E)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Ege University, Izmir, Turkey.

Ahmet Sezer (A)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Cukurova University, Adana, Turkey.

Sevgi Keles (S)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.

Figen Celebi Celik (FC)

Department of Pediatric Allergy and Immunology, Dr. Behcet Uz Children's Education and Research Hospital, University of Health Sciences, Izmir, Turkey.

Aylin Ozhan Kont (AO)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey.

Betul Gemici Karaaslan (BG)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Asena Pinar Sefer (AP)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Zuhal Karali (Z)

Department of Pediatric Immunology and Rheumatology, Faculty of Medicine, Uludag University, Bursa, Turkey.

Elif Arik (E)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.

Esra Ozek Yucel (EO)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey; Department of Pediatric Allergy and Immunology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Omer Akcal (O)

Department of Pediatric Allergy and Immunology, Gaziantep Cengiz Gokcek Gynecology and Pediatrics Hospital, Gaziantep, Turkey.

Leman Tuba Karakurt (LT)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.

Melek Yorgun Altunbas (MY)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Koray Yalcin (K)

Department of Pediatric Hematology and Oncology, Pediatric Bone Marrow Transplant Unit, Medical Park Goztepe Hospital, Bahcesehir University, Istanbul, Turkey; Department of Medical Biotechnology, Institute of Health Science, Acibadem University, Istanbul, Turkey.

Vedat Uygun (V)

Department of Pediatric Hematology and Oncology, Pediatric Bone Marrow Transplant Unit, Medical Park Antalya Hospital, Istinye University, Antalya, Turkey.

Gulcihan Ozek (G)

Department of Pediatric Hematology and Oncology, Pediatric Bone Marrow Transplant Unit, Ege University, Izmir, Turkey.

Royala Babayeva (R)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Cigdem Aydogmus (C)

Department of Pediatric Allergy and Immunology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, Istanbul, Turkey.

Dilek Ozcan (D)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Cukurova University, Adana, Turkey.

Ozlem Cavkaytar (O)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.

Ozlem Keskin (O)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.

Sara Sebnem Kilic (SS)

Department of Pediatric Immunology and Rheumatology, Faculty of Medicine, Uludag University, Bursa, Turkey.

Ayca Kiykim (A)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Tugba Arikoglu (T)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Mersin, Turkey.

Ferah Genel (F)

Department of Pediatric Allergy and Immunology, Dr. Behcet Uz Children's Education and Research Hospital, University of Health Sciences, Izmir, Turkey.

Nesrin Gulez (N)

Department of Pediatric Allergy and Immunology, Dr. Behcet Uz Children's Education and Research Hospital, University of Health Sciences, Izmir, Turkey.

Sukru Nail Guler (SN)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.

Neslihan Edeer Karaca (NE)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Ege University, Izmir, Turkey.

Ismail Reisli (I)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.

Necil Kutukculer (N)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Ege University, Izmir, Turkey.

Derya Ufuk Altintas (DU)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Cukurova University, Adana, Turkey.

Ahmet Ozen (A)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Elif Karakoc Aydiner (EK)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Safa Baris (S)

Department of Pediatric Allergy and Immunology, Faculty of Medicine, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey; The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey. Electronic address: safabaris@hotmail.com.

Classifications MeSH