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Review Article

Double-negative T cells in pediatric rheumatic diseases

Dimitri Poddighe^1,2  , Tilektes Maulenkul^1,2, Kuanysh Dossybayeva¹, Gulsamal Zhubanova¹, Zaure Mukusheva³, Lyudmila Akhmaltdinova¹

¹Department of Medicine, Nazarbayev University School of Medicine (NUSOM), Astana, Kazakhstan
²Clinical Academic Department of Pediatrics, National Research Center for Maternal and Child Health, University Medical Center, Astana, Kazakhstan
³Program of Pediatric Rheumatology, Clinical Academic Department of Pediatrics, University Medical Center, Astana, Kazakhstan

Correspondence Dimitri Poddighe ,Email: dimitri.poddighe@nu.edu.kz

Received: December 23, 2023; Revised: June 5, 2024   Accepted: June 11, 2024.

Abstract

Double-negative (CD4-CD8-) T (DNT) cells have been implicated in Autoimmune Lymphoproliferative Syndrome (ALPS), where their expansion inside the circulating pool of T cells represents a diagnostic criterion. Recent experimental evidence has supported the immunomodulatory roles of DNT cells, and studies in adult patients have suggested that they may be altered in some immune-mediated conditions. This study aimed to retrieve available data on circulating DNT cells in pediatric rheumatic disorders that do not arise in the context of ALPS through a systematic literature review of three scientific databases (PubMed, Scopus, and Web of Science). The final output of the systematic literature search consisted of eight manuscripts, including cross-sectional (n=6) and longitudinal (n=2) studies. Overall, the pooled population of patients includes children affected with pediatric Systemic Lupus Erythematosus (n=104), Juvenile Idiopathic Arthritis (n=92), Behçet's disease (n=15), mixed connective tissue disease (n=8), Juvenile Dermatomyositis (n=6), and Kawasaki disease/multisystem inflammatory disease in children (n=1 and n=14, respectively); moreover, one study also included 11 children with a high titer of antinuclear antibody but no diagnosis of rheumatic disease. All studies except one included a control group. The number of DNT cells were increased in most studies of children with rheumatic diseases. Even if such a limited number of studies and their great heterogeneity in several methodological aspects do not allow for reliable conclusions about the relevance of DNT cells in specific rheumatic conditions in children, this cell population deserves further investigation in this pathological setting through well-designed clinical studies.

Keywords :Double-negative T cells, Child, Rheumatic disorders, Juvenile idiopathic arthritis, Systemic lupus erythematosus, unconventional T lymphocytes