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Peer reviewedOpen accessRheumatic fever

CXCR3 is associated with T-cell-induced heart damage in acute rheumatic fever.

Nature communications·

Middleton FM, McGregor R, Lorenz N, Kilian S, Brooks AES, Park SM, Ramiah C, Tresidder J, Barnett TC, Serralha M, Martin WJ, Chan Mow F, Pearson G, Mayo M, Broadhurst DI, Bennett J, Brink J, Wilson NJ, Ralph AP, Webb RH, Dunbar PR, Carapetis J, Moreland NJ

DOI
10.1038/s41467-026-71094-8
PMID
41916981
PMCID
PMC13201666
OpenAlex
W7146956073
Study type
Case-control study
Publisher
Publisher unavailable
Article type
journal-article
Integrity
current

Why this research matters now

The findings identify a perturbed T cell compartment in acute rheumatic fever and provide a mechanistic rationale for exploring currently available immune-modulating therapies to treat the disease and prevent progressive cardiac damage.

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Structured evidence summary

Research question

The study aimed to identify circulating immune markers and cells that distinguish acute rheumatic fever from other severe pediatric inflammatory conditions and healthy controls, and to inform potential therapeutic targets.

Study design

Case-control study comparing participants with definite acute rheumatic fever to children with other severe acute pediatric conditions and matched healthy controls. Circulating immune molecules and cells were profiled, and immunofluorescence imaging was performed on rheumatic valve tissue.

Population and setting

Pediatric participants with definite acute rheumatic fever, compared to children with other severe acute inflammatory conditions and healthy matched controls.

Main findings

Acute rheumatic fever showed elevated serum IL-6 and increased circulating CD4+ T cells similar to other inflammatory conditions, but was distinguished by elevated CCL5 and IgG3, reduced CXCR3 expression in T cells, and reduced circulating regulatory T cells. Immunofluorescence confirmed CXCR3-mediated T cell tissue homing in rheumatic valve tissue.

Public-health relevance

The findings identify a perturbed T cell compartment in acute rheumatic fever and provide a mechanistic rationale for exploring currently available immune-modulating therapies to treat the disease and prevent progressive cardiac damage.

Important limitations

This summary is limited to the supplied single-article abstract and metadata. Complete interpretation of study limitations, including sample size, generalizability, and methodological constraints, requires access to the full paper.

GIDS interpretation

The study characterizes immune pathways in acute rheumatic fever for potential therapeutic targeting. The case-control design aids in understanding disease mechanisms but does not establish causality or connect to surveillance trends.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 5 auditable classifier relationships to diseases, places, topics, and study design.

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