Revisiting double-negative T cells in autoimmune lymphoproliferative immunodeficiencies: a case series

• Mahnaz Jamee ^[1] ; Samin Sharafian ^[1] ; Narges Eslami ^[1] ; Shideh Namazi Bayegi ^[4] ; Mohammad Keramatipour ^[2] ; Mohamad Nabavi ^[3] ; Sima Shokri ^[3] ; Marjan Shakiba ^[1] ; Bibi Shahin Shamsian ^[1] ; Hassan Abolghasemi ^[1] ; Kurosh Vahidshahi ^[1] ; Ghamartaj Khanbabaee ^[1] ; Shahnaz Armin ^[1] ; Zahra Chavoshzadeh ^[1] ; Mehrnaz Mesdaghi ^[1]
  1. [1] Shahid Beheshti University of Medical Sciences

     Shahid Beheshti University of Medical Sciences

     Irán

     
  2. [2] Tehran University of Medical Sciences

     Tehran University of Medical Sciences

     Irán

     
  3. [3] Iran University of Medical Sciences

     Iran University of Medical Sciences

     Irán

     
  4. [4] Department of Allergy and Immunodeficiency, Massoud Medical Laboratory, Tehran, Iran

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• Localización: Allergologia et immunopathologia: International journal for clinical and investigate allergology and clinical immunology, ISSN-e 1578-1267, ISSN 0301-0546, Vol. 52, Nº. 5, 2024, págs. 6-14
• Idioma: inglés
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  • Background: Elevated level of double-negative T (DNT) cells is a historical hallmark of autoimmune lymphoproliferative syndrome (ALPS) diagnosis. However, the peripheral blood level of DNT cells might also be compromised in autoimmune lymphoproliferative immunodeficiencies (ALPID) other than ALPS, inattention to which would increase the delay in diagnosis of the underlying genetic defect and hinder disease-specific treatment.

    Materials and Methods: This cross-sectional study recruited patients suffering from ALPID (exclusion of ALPS) with established genetic diagnosis. Following thorough history taking, immunophenotyping for lymphocyte subsets was performed using flowcytometry.

    Results: Fifteen non-ALPS ALPID patients (60% male and 40% female) at a median (interquartile range: IQR) age of 14.0 (7.6–21.8) years were enrolled. Parental consanguinity and family history of immunodeficiency were present in 8 (53.3%) patients. The median (IQR) age at first presentation, clinical and molecular diagnosis were 18 (4–36) months, 8.0 (4.0–17.0) years, and 9.5 (5.0–20.9) years, respectively. Molecular defects were observed in these genes: LRBA (3, 20%), CTLA-4 (2, 13.3%), BACH2 (2, 13.3%), AIRE (2, 13.3%), and FOXP3, IL2Rβ, DEF6, RASGRP1, PIK3CD, and PIK3R1 each in one patient (6.7%). The most common manifestations were infections (14, 93.3%), autoimmunity (12, 80%), and lymphoproliferation (10, 66.7%). The median (IQR) count of white blood cells (WBCs) and lymphocytes were 7160 (3690–12,600) and 3266 (2257–5370) cells/mm3, respectively. The median (IQR) absolute counts of CD3+ T lymphocytes and DNTs were 2085 (1487–4222) and 18 (11–36) cells/mm3, respectively. Low lymphocytes and low CD3+ T cells were observed in 3 (20%) patients compared to normal age ranges. Only one patient with FOXP3 mutation had DNT cells higher than the normal range for age.

    Conclusions: Most non-ALPS ALPID patients manifested normal DNT cell count. For a small subgroup of patients with high DNT cells, defects in other IEI genes may explain the phenotype and should be included in the diagnostic genetic panel.