ABSTRACT
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: 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: 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: 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+ T-cell counts were observed in patients with the RFX5 mutations compared to RFXANK-mutant patients (p=0.006 and p=0.009, respectively). CONCLUSION: 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.
Subject(s)
Allergens , Pyroglyphidae , Animals , Child , Humans , Dermatophagoides pteronyssinus , Immunotherapy , Dust , Antigens, Dermatophagoides , Desensitization, ImmunologicABSTRACT
AIM: This study aimed to present the results of newborns who were referred to advanced audiology centers after newborn hearing screening, and to determine concordance of our results with the American Academy of Pediatrics guidelines about the ages of hearing loss, aid fitting, and cochlear implantation. MATERIALS AND METHODS: A total of 7502 newborns were screened in Gaziosmanpasa Taksim Research and Training Hospital between March 2014 and June 2016 using the transient otoacustic emissions test as the first two steps and automated auditory brainstem response test for the third step. Newborns who had risk factors were screened using the automated auditory brainstem response only. Newborns who failed the screening tests were referred to advanced audiology centers. RESULTS: Of the 7502 newborns, 6736 (90%) completed the screening. The ratio of hearing loss was 0.08%. Six of 62 newborns who failed auditory brainstem response test and were referred to advanced audiology centers had severe bilateral hearing loss. One of the patients was not fitted with a hearing aid because the family refused it. The other one was not fitted an aid and did not undergo cochlear implantation because of severe and treatment-resistant acute otitis media. The age of diagnosis for the rest was before three months, and except for one patient, hearing aid fitting was before six months. The age of cochlear implantation was 12 months for two patients and 14 months for two patients. CONCLUSION: Ninety percent of patients completed the screening, the age of diagnosis for hearing loss was before three months and aid fitting was before six months, except for one patient. The results of the study were compatible with the diagnosis and treatment guidelines of the American Academy of Pediatrics.
