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Regulatory T and B cells in pediatric Henoch-Schonlein purpura: friends or foes?


ABSTRACT:

Background and objectives

Henoch-Schönlein purpura (HSP) is the most common immunoglobulin A-mediated systemic vasculitis in childhood. We studied immune dysregulation in HSP by analyzing regulatory T (Treg), T helper 3 (Th3), and regulatory B cell (Breg) subpopulations that might intervene in immune activation, IgA production, and HSP clinical manifestations.

Methods

This prospective study included 3 groups of children: 30 HSP on acute phase, 30 HSP on remission, and 40 healthy controls (HCs) matched on age. Treg, Breg, and Th3 were analyzed by flow cytometry. Serum immunoglobulin and cytokine levels were quantified by ELISA and Luminex.

Results

Treg frequencies were higher in acute HSP than in remitting HSP and HCs (6.53% [4.24; 9.21] vs. 4.33% [3.6; 5.66], p = 0.002, and vs. 4.45% [3.01; 6.6], p = 0.003, respectively). Activated Th3 cells (FoxP3 + Th3 cells) tend to be more abundant in HSP than in HCs (78.43% [50.62; 80.84] vs. 43.30% [40.20; 49.32], p = 0.135). Serum IgA, IL-17, and latency-associated peptide (a marker of the anti-inflammatory cytokine TGF-beta production) were significantly and inflammatory cytokines TNF-alpha, IL-1-beta, and IL-6 were non-significantly higher in HSP than HCs. Bregs were identical between the groups, but, in patients with renal impairment, Breg percentage was lower compared to those without. Treg removal in PBMC culture resulted in an increase in IgA production in HSP proving a negative regulatory role of Tregs on IgA production.

Conclusions

In pediatric HSP, immune activation persists in spite of an increase in Th3 and Tregs. Th3 could be involved in IgA hyperproduction, inefficiently downregulated by Tregs. Lack of Bregs appears linked to renal impairment.

SUBMITTER: Filleron A 

PROVIDER: S-EPMC10870453 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Regulatory T and B cells in pediatric Henoch-Schönlein purpura: friends or foes?

Filleron Anne A   Cezar Renaud R   Fila Marc M   Protsenko Nastassja N   Van Den Hende Kathleen K   Jeziorski Eric E   Occean Bob B   Chevallier Thierry T   Corbeau Pierre P   Tran Tu Anh TA  

Arthritis research & therapy 20240216 1


<h4>Background and objectives</h4>Henoch-Schönlein purpura (HSP) is the most common immunoglobulin A-mediated systemic vasculitis in childhood. We studied immune dysregulation in HSP by analyzing regulatory T (Treg), T helper 3 (Th3), and regulatory B cell (Breg) subpopulations that might intervene in immune activation, IgA production, and HSP clinical manifestations.<h4>Methods</h4>This prospective study included 3 groups of children: 30 HSP on acute phase, 30 HSP on remission, and 40 healthy c  ...[more]

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