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. 2022 Sep 5;7(10):2166–2170. doi: 10.1182/bloodadvances.2021006797

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Figure 2. — Hypothetical schematic representation of proposed interplay between cytokine biomarkers and immune cells in wAIHA. Activated macrophages in spleen and/or liver produce wAIHA biomarkers IL-6, IL-8/CXCL8, IL-10, MCP-1/CXCL2, IP-10/CXCL10, TNFα, and MDC/CCXL22. IL-6, TNFα, and IL-10 dysregulate the humoral immune response in GC. TNFα downregulates T regulatory (Treg) cells in the periphery and Tfr cells in the GC. IL-10 is essential for generation of GC B-cell response; IL-6, produced by activated macrophages and plasmablast B cells, enhances gene transcription and function of Tfh cells that pushes and maintains autoantibody production. IL-8/CXCL8 may play a pivotal role in inducing autoantigens on the RBC because of ROS-induced oxidative stress. MCP-1 and IP-10 may indicate severity of wAIHA as MCP-1 is produced from macrophages owing to antibody-sensitized RBCs binding to FcRs, and IP-10 is necessary for effector T-cell generation and may influence Tfh effector cells as well. Down regulation of MDC may help to shift the T_H2 response to a more inflammatory T_H1 response and help drive the wAIHA. Cytokine/chemokines in red are potential biomarkers of wAIHA.