Clinical and Immunological Spectrum of MHC Class I Deficiency: Insights from a Long-Term Cohort with Two Novel Mutations

Şule Haskologlu^1*Kamile Aydan Ikinciogullari¹Candan Islamoglu¹Sevgi Kostel Bal²Deniz Bayrakoglu¹Serife Erdem³Ceren Karahan⁴Omur Ardeniz⁵Caner Aytekin⁶Aylin Heper⁷Serdar Ceylaner⁸Figen Dogu¹

• ¹Department of Pediatric Immunology and Allergy, Ankara Universitesi Tip Fakultesi, Ankara, Türkiye
• ²Department of Pediatric Immunology and Allergy, TC Saglik Bakanligi Ankara Gulhane Egitim ve Arastirma Hastanesi, Ankara, Türkiye
• ³Betul-Ziya Eren Genome and Stem Cell Center, Erciyes Universitesi Tip Fakultesi, Kayseri, Türkiye
• ⁴Department of Medical Microbiology, Ankara Universitesi Tip Fakultesi, Ankara, Türkiye
• ⁵Department of Internal Medicine, Division of Allergy and Immunology, Ege Universitesi Tip Fakultesi, Izmir, Türkiye
• ⁶Department of Pediatric Immunology and Allergy, SBU Ankara Dr Sami Ulus Kadin Dogum Cocuk Sagligi ve Hastaliklari Egitim ve Arastirma Hastanesi, Ankara, Türkiye
• ⁷Department of Medical Pathology, Ankara Universitesi Tip Fakultesi, Ankara, Türkiye
• ⁸Intergen Genetik Hastaliklar Tani Merkezi, Ankara, Türkiye

Background: Major histocompatibility complex (MHC) Class I deficiency is a rare form of primary immunodeficiency that typically presents with recurrent sinopulmonary infections, bronchiectasis, and granulomatous skin lesions during late childhood or adolescence. Methods: This retrospective study describes the clinical, immunological, and long-term follow-up data of 11 patients diagnosed MHC Class I deficiency. Results: The cohort included 11 patients (6 males, 5 females) with a median age of 26 years (range 19–44). The median age at diagnosis was 19 years, with a diagnostic delay of 14 years. Bronchiectasis was seen in 10 patients, granulomatous skin lesions in 6, uveitis in 5, and nasal septum perforation in 3. All but one patient survived during a median follow-up of 11 years. HLA-ABC expression ranged from 0% to 73%, with persistently low mean fluorescence intensity (0.4–3.8). IgM levels were reduced in 7 patients. Ten patients were persistently positive for anti-rubella IgM, including all six with granulomatous skin lesions. Immunophenotyping revealed reduced CD3⁺ (n=2), CD4⁺ (n=3), CD8⁺ (n=3), CD19⁺ (n=5), CD3⁻CD16⁺CD56⁺ (n=3), CD19+ IgM-27+ IgD- (switched memory B cells) (n=7), and CD19+ IgM-27+ IgD+ (marginal zone B cells) (n=8). All patients had elevated γδ+ T cells, and NK cells were reduced in three. Seven patients had TAP1 and four had TAP2 mutations, with no significant genotype–phenotype differences. Conclusion: MHC Class I deficiency presents a broad clinical spectrum from asymptomatic to life-threatening disease. Granulomatous tissue damage and uveitis contributed to morbidity. Persistent rubella-specific IgM in most patients, including those without granulomas, is a novel serologic finding that may reflect altered antiviral immunity. Its clinical significance remains uncertain and, further studies with tissue-based viral detection are needed to clarify this observation.