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. 2023 May 23;7(10):2166-2170.
doi: 10.1182/bloodadvances.2021006797.

The chemokines IP-10/CXCL10 and IL-8/CXCL8 are potential novel biomarkers of warm autoimmune hemolytic anemia

Affiliations

The chemokines IP-10/CXCL10 and IL-8/CXCL8 are potential novel biomarkers of warm autoimmune hemolytic anemia

Donald R Branch et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Identification of plasma cytokines altered in wAIHA. Cytokines found significantly changed between HC (n = 36) and wAIHA patients (n = 54) are shown. HC are also compared with nontransfused (nt-wAIHA, n = 24) or transfused (t-wAIHA, n = 24) patient subsets (transfusion status was not available for 6 patients). Transfusion status did not affect significance with the exception of IL-6, which was not different from HC in nt-wAIHA patients. Shown here for visual comparison are the original data plotted on log scale. The geographic mean (equivalent to mean of log-transformed data) and 95% confidence intervals of the mean is shown for each cytokine. Significance bars above data indicate the degree of difference between HC and wAIHA; ∗P <.05; ∗∗P <.01; ∗∗∗P <.001; ∗∗∗∗P <.0001 were determined using t-test for log-normal cytokines, and Mann Whitney nonparametric analysis for nonlog normal cytokines. Supplemental Methods provides the details of statistical analysis of log-transformed cytokine data.
Figure 2.
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 TH2 response to a more inflammatory TH1 response and help drive the wAIHA. Cytokine/chemokines in red are potential biomarkers of wAIHA.

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