Variable clinical presentation of hypomorphic DCLRE1C deficiency from childhood to adulthood
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Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
John Wiley and Sons Inc
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Background: In this study, we aimed to report long-term follow-up of our pediatric and adult patients with DCLRE1C (DNA cross-link repair 1C) hypomorphic mutation who were diagnosed leaky severe combined immunodeficiency (SCID). Methods: Eighteen patients (13 children and five adults), aged between 6 and 29 years were included. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, regulator T (Treg) cell ratios/markers, and cytokines, were assessed before and after hematopoietic stem cell transplantation (HSCT) and compared with healthy controls. Results: Recurrent infections (78%) and skin manifestations (61%) such as granulomatous skin lesions, warts, and vitiligo were the most common clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17%. Most patients had low serum IgA and B- and T-cell lymphopenia at the first admission. Recent thymic emigrants (RTE), T<inf>naive</inf>, B<inf>naive</inf>, CD56dimCD16+ cell ratios were significantly lower in the patients than in control; however, follicular helper T T<inf>FH</inf> and Th1 [interferon gamma (IFN-?)] cell ratios were significantly higher than the control. Although, Treg ratio and its functional receptors tend to be high but not significant. Eleven patients (61.1%) were treated with HSCT. Median follow-up times of transplant patients was 56 (9–67) months. Conclusion: Patients with hypomorphic DCLRE1C mutations may present with variable clinical and laboratory findings at different ages. Our study showed a helper T (Th)1-dominant immune response before and after HSCT. Increased IFN-? and T<inf>FH</inf> cells ratio could be a reason of chronic inflammation and autoimmunity developing before and after HSCT. Long-term follow-up of these patients after HSCT will help to better understand the disease and its pathophysiology. © 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Açıklama
Anahtar Kelimeler
artemis, combined immune deficiency, DCLRE1C, leaky severe combined immunodeficiency, severe combined immune deficiency
Kaynak
Pediatric Allergy and Immunology
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
35
Sayı
10
