Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 1;52(5):6-14.
doi: 10.15586/aei.v52i5.1115. eCollection 2024.

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

Mahnaz Jamee  1   2 , Samin Sharafian  2 , Narges Eslami  2 , Shideh Namazi Bayegi  3   4 , Mohammad Keramatipour  5 , Mohamad Nabavi  6 , Sima Shokri  6 , Marjan Shakiba  7 , Bibi Shahin Shamsian  8 , Hassan Abolghasemi  8 , Kurosh Vahidshahi  9 , Ghamartaj Khanbabaee  10 , Shahnaz Armin  11 , Zahra Chavoshzadeh  12 , Mehrnaz Mesdaghi  1   2   13
Affiliations

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

Mahnaz Jamee et al. Allergol Immunopathol (Madr). .

Abstract

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 BD FACS CaliburTM 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.

Keywords: ALPID; ALPS; flowcytometry; immune dysregulation; inborn error of immunity; primary immune -regulatory disorder.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. 1. Shajari A, Zare Ahmadabadi A, Ashrafi MM, Mahdavi T, Mirzaee M, Mohkam M, et al. Inborn errors of immunity with kidney and urinary tract disorders: a review. Int Urol Nephrol. 2024; 56(6):1965–72. 10.1007/s11255-023-03907-4 - DOI
    1. 2. Consonni F, Gambineri E, Favre C. ALPS, FAS, and beyond: from inborn errors of immunity to acquired immunodeficiencies. Ann Hematol. 2022; 101(3):469–84. 10.1007/s00277-022-04761-7 - DOI
    1. 3. Magerus A, Rensing-Ehl A, Rao VK, Teachey, DT, Rieux-Laucat F, Ehl S. Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders. J Allergy Clin Immunol. 2024; 153(1):67–76. 10.1016/j.jaci.2023.11.004 - DOI
    1. 4. Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. J Clin Immunol. 2022; 42(7):1508–20. 10.1007/s10875-022-01352-z - DOI
    1. 5. Cox F, Bigley V, Irvine A, Leahy R, Conlon N. PAMI syndrome: two cases of an autoinflammatory disease with an ALPS-like phenotype. J Clin Immunol. 2022; 42(5):955–8. 10.1007/s10875-022-01265-x - DOI

LinkOut - more resources