Variable Clinical Presentation of DCLRE1C Deficiency from Childhood to Adulthood

Abstract

Abstract In this study, we aimed to report long term follow up of our patients with DCLRE1C hypomorphic mutation including children and adults with leaky SCID. Eighteen patients, aged 6–29 (11 children, 7 adults), were enrolled in the study. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, Treg cell ratios/markers, and cytokines, were assessed pre- and post-HSCT and compared with healthy controls. Recurrent infections (78%) and skin findings including granulomatous skin lesions, warts, vitiligo (61%) were the most frequently observed clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17% of the patients. Most patients had low serum IgA and B and T cell lymphopenia at the first admission. RTE, Tnaive, Bnaive, CD56dimCD16+ cell ratios were significantly lower in the patients compared to control, however, TFH and Th1 (IFN-γ) 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. Mean follow-up times of transplant patients was 46.41± 25.77 months. Patients with hypomorphic DCLRE1C mutations can present with variable clinical and laboratory findings at different ages. Our study showed a Th1 dominant immune response in patients before and after HSCT. Increased IFN-γ and TFH cells ratio could be a reason for chronic inflamation and autoimmunity developing before and after HSCT. Long term follows up of those patients after HSCT will help to better understanding of the disease and its pathophysiology.