Abstract
IntroductionIdentifying T-cell activation, the hallmark of multiple hyperinflammatory diseases like HLH and immune dysregulation disorders (IDS) like LRBA deficiency, is critical for diagnosis, management, and monitoring treatment response for patients with immune activation driven disease processes. Soluble Interleukin 2 Receptor (sIL2R) is an established systemic marker for T-cell activation but the clinical availability of sIL2R testing is limited. sIL2R is also not a reliable marker of T-cell activation in patients with eosinophilia or T-cell lymphoma. A recent study by Chaturvedi et.al has demonstrated the utility of flow-based T-cell activation assessment in differentiating HLH from sepsis. However, its utility in defining and quantifying T-cell activation across the hyperinflammatory spectrum and its correlation with sIL2R has not yet been established. MethodsA total of 125 samples were collected either at disease onset (n = 81) or at follow-up (n = 44) from 85 human subjects. Paired plasma sIL2R and T-cell activation markers were prospectively evaluated in patients with suspected HLH (n = 79) or IDS (n = 46). Flow cytometry-based T-cell activation was evaluated in different T-cell sub-compartments by the coexpression of HLA-DR and CD38 surface markers. ResultsEvaluation of T-cell activation measured by HLADR+CD38high in healthy controls (HCs) and different hyperinflammatory/ immune regulatory disorders revealed that HCs have less than 8% of T-cell activation in CD8 + Teffector memory (TEM) and less than 4% for activation in the CD4+ TEM compartments. In patients with suspected hyperinflammatory/ immune regulatory disorders, we identified significant correlation of direct T-cell activation with plasma sIL2R level in different T-cell subsets, CD3 (r = 0.44, p < 0.0001), CD4 (r = 0.41, p < 0.0001), CD8 (r = 0.45, p < 0.001), CD4 TEM (Teffector memory) (r = 0.53, p < 0.001), and CD8 TEM (r = 0.53, p < 0.0001).The strongest correlation between HLADR+CD38high with sIL2R level was noted in CD4+ TEM and CD8+ TEM compartments (Figure 1). [Display omitted] [Display omitted] ConclusionsFlow cytometry-based direct assessment of HLADR+ CD38high in T cells subsets can reliably quantify T-cell activation and strongly correlate with sIL2R level across a spectrum of different hyperinflammatory and immune dysregulation disorders.
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