Research Article: Transcriptomic analysis identifies STAT1 as a potential key transcriptional regulator of T-cell dysfunction in AIHA
Abstract:
Autoimmune hemolytic anemia (AIHA) is characterized by antibody-mediated red blood cell destruction. T-cell dysfunction is implicated in its pathogenesis, but the underlying transcriptional mechanisms remain poorly understood.
We analyzed peripheral CD4+ and CD8+ T cells from patients with primary warm AIHA and healthy controls by flow cytometry and RNA sequencing. Transcription factor enrichment, ChEA3, an external AIHA Treg dataset, immune-function scores, and clinical correlations were examined. LDH was measured after ex vivo treatment with resveratrol or fludarabine. In an AIHA mouse model, we assessed LDH, spleen weight, erythrocyte-bound IgG, and peripheral T-cell STAT1 and pSTAT1 fluorescence after treatment with resveratrol or fludarabine.
The AIHA group had a higher proportion of peripheral CD8+ T cells and altered CD4+ and CD8+ T cell transcriptional profiles. Transcription factor analysis identified STAT1 as a shared regulatory candidate in both CD4+ and CD8+ T cells. In the mouse experiment, LDH, spleen weight, erythrocyte-bound IgG fluorescence, and peripheral CD4+ and CD8+ T cell STAT1 and pSTAT1 fluorescence were higher in the AIHA group than in controls and lower in the resveratrol and fludarabine groups than in untreated AIHA mice.
Our study identifies STAT1 as a potential transcriptional regulator associated with T-cell dysfunction and hemolytic activity in AIHA. These findings support further investigation of STAT1-associated signaling as a possible therapeutic target.
Introduction:
Autoimmune hemolytic anemia (AIHA) is characterized by antibody-mediated red blood cell destruction. T-cell dysfunction is implicated in its pathogenesis, but the underlying transcriptional mechanisms remain poorly understood.
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