A predictive model for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a severe hyperinflammatory disorder induced by overactivation of macrophages and T cells. This study aims to identify the risk factors for the progression from infectious mononucleosis (EBV-IM) to EBV-HLH, by analyzing the laboratory parameters of patients with EBV-IM and EBV-HLH and constructing a clinical prediction model. The outcome of this study carries important clinical value for early diagnosis and treatment of EBV-HLH.
A retrospective analysis was conducted on 60 patients diagnosed with EBV-HLH and 221 patients diagnosed with EBV-IM at our hospital between November 2018 and January 2024. Participants were randomly assigned to derivation and internal validation cohorts in a 7:3 ratio. LASSO regression and logistic regression analyses were employed to identify risk factors and construct the nomogram.
Ferritin (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001), CD3-CD16+CD56+% (OR, 0.011; 95% CI, 0-0.467; P=0.011), anti-EBV-NA-IgG (OR, 57.370; 95%CI, 2.976-1106.049; P=0.007), IL-6 (OR, 71.505; 95%CI, 2.118-2414.288; P=0.017), IL-10 (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001) were identified as independent predictors of EBV-HLH. The prediction model demonstrated excellent discriminatory capability evidenced by an AUC of 0.997 (95% CI,0.993-1.000). When visualized using a nomogram, the ROC curves for the derivation and validation cohorts exhibited AUCs of 0.997 and 0.993, respectively. These results suggested that the model was highly stable and accurate. Furthermore, calibration curves and clinical decision curves indicated that the model possessed good calibration and offered significant clinical benefits.
The nomogram, which was based on these five predictors, exhibited robust predictive value and stability, thereby can be used to aid clinicians in the early detection of EBV-HLH.
Huang R
，Wu D
，Wang L
，Liu P
，Zhu X
，Huang L
，Chen M
，Lv X
... -
《Frontiers in Immunology》
Effect of Epstein-Barr virus on macrophage M2/M1 migration and EphA2 expression in adverse drug reactions.
This study aims to investigate the effect of Epstein-Barr virus (EBV) reactivation or EBV reactivation with dexamethasone (DXM) in patients with adverse drug reactions (ADRs) through evaluating the levels of monocyte, macrophage M2/M1, and cytokines, and investigating whether expression of EBV receptor EphA2 could specifically influence EBV activation in ADRs. We performed a prospective longitudinal study to analyze the monocytes, macrophages, M2/M1 ratio, and cytokines, including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IFN-β, C-X-C motif chemokine ligand (CXCL)9, and CXCL10, in patients with maculopapular exanthema (MPE) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and control groups after disease onset. Skin biopsy samples from these patients were subjected to hematoxylin and eosin (H&E) staining to examine tissue architecture and inflammatory cell infiltration, as well as Epstein-Barr virus-encoded RNA (EBER) staining to detect the presence of EBV within the skin lesions. Peripheral blood mononuclear cells collected from these patients were co-cultured with EBV or EBV combined with DXM to assess the impact on monocytes, macrophages, the M2/M1 ratio, and the associated cytokine profile. Furthermore, we sought to identify which cytokines might be crucial in mediating the interaction between the M2/M1 ratio and EBV. EPhA2 expression was evaluated to determine its role in the reactivation of EBV and its correlation with increased viral load in MPE and SJS/TEN patients. Selective depletion of macrophages occurred during the acute stage of SJS/TEN, while a shift towards M2 macrophages was observed in MPE. Both IFN-β and CXCL9 levels were elevated in MPE and SJS/TEN. Additionally, our study demonstrated the presence of EBV in the skin lesions of SJS/TEN and MPE patients through H&E and EBER staining, confirming EBV's involvement in these conditions. Activation of EBV and EBV combined with DXM led to a shift from M1 to M2 macrophages, accompanied by increased levels of IL-4, IFN-γ, and CXCL9 in MPE and SJS/TEN, compared to healthy individuals. Specifically, EBV combined with DXM primarily drove IFN-γ and IL-4 expansions in MPE, while CXCL9 was predominantly elevated in SJS/TEN. The increased IL-4 levels were associated with the relative rise in EBV viral loads after EBV combined with DXM stimulation. Furthermore, EphA2 expression in monocytes was significantly higher in SJS/TEN and MPE patients compared to controls, with further increases on EBV stimulation. This elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients. The gradual shift from M1 to M2 cell development observed during the clinical course of MPE and SJS/TEN is mediated by the predominance of EBV and EBV with DXM at the acute stage, leading to elevated IL-4, IFN-γ, and CXCL9 levels, which may exacerbate allergic reactions. The elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients, suggesting that adverse drug reactions may induce EPhA2 expression, facilitating EBV replication and activation. EphA2 could thus serve as an indicator of EBV activation and a marker for assessing the risk of EBV in patients with adverse drug reactions.
An R
，Sun DJ
，Lei HX
，He AR
，Tu Y
，Tang JT
... -
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ResearchGate
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钛学术
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