暖性自身免疫性溶血性贫血（wAIHA）是一种罕见的后天性自身免疫性疾病，其主要通过抗体靶向红细胞介导。CD4 T辅助（Th）细胞的参与并未充分研究，大多数结果来自动物模型的推测。在这里，我们对人体wAIHA中的效应T淋巴细胞（Teff）和调节性T细胞（Treg）进行了定量化，并结合功能和转录组学分析了Treg。我们观察到，Teff向Th17极化转变，与增加的血清IL-17浓度相一致，该浓度与红细胞破坏参数（即LDH和胆红素水平）呈正相关。我还观察到循环中Treg的减少，尤其是效应Treg，并伴随着功能缺陷，如其抑制Teff增殖功能的减弱。Treg缺陷与Foxp3的减少表达相关，Foxp3是维持Treg表型稳定性和抑制功能的主要转录因子。Treg的转录组学分析显示激活了TNF-α通路，并且与增加的血清TNF-α浓度相关，这种浓度是对照组的两倍。Treg的转录组学分析还提示，翻译后修饰机制可能导致了Foxp3的下调和Treg的功能异常。由于TNF-α参与了AIHA期间免疫耐受的破裂，抑制TNF-α可能具有一定的意义。因此，我们在体外研究了fostamatinib，一种SYK抑制剂的影响，并且我们显示出除了抑制单核细胞对红细胞的吞噬作用外，fostamatinib还能减弱TNF-α的产生，因此在wAIHA中可能作为一种有希望的多靶向治疗方法。

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T helper (Th) cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA. We observed a shift of Teff toward a Th17 polarization concordant with an increase in serum IL-17 concentration that correlates with RBC destruction parameters, namely LDH and bilirubin levels. A decrease in circulating Treg, notably effector Treg, associated with a functional deficiency, as represented by their decrease capability to inhibit Teff proliferation, were also observed. Treg deficiency was associated with a reduced expression of Foxp3, the master transcription factor known to maintain the Treg phenotype stability and suppressive functions. Transcriptomic profiling of Tregs revealed activation of the TNF-α pathway, which was linked to increased serum TNF-α concentrations that were twice as high as in controls. Treg transcriptomic profiling also suggested that post-translational mechanisms possibly accounted for Foxp3 downregulation and Treg dysfunctions. Since TNF-α participates in the rupture of immune tolerance during AIHA, its inhibition could be of interest. To this end, the effects of fostamatinib, a SYK inhibitor, were investigated in vitro, and we showed that besides the inhibition of erythrocyte phagocytosis by monocytes, fostamatinib is also able to dampen TNF-α production, thus appearing as a promising multitargeting therapy in wAIHA.