Cytokine profiles as novel diagnostic markers of Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis in children

Han, Xiucui; Ye, Qing; Zhang, Weiying; Tang, Yuanyue; Xu, Xiao‐Jun; Zhang, Ting

doi:10.1016/j.jcrc.2017.02.018

Cited by 35 publications

(25 citation statements)

References 27 publications

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“…No report has described the changes in serum cytokine levels in cases of bacteria-associated HLH; therefore, we measured the serial changes in serum cytokines that have been reported previously in cases of virus-associated HLH. In the present case as well, the levels of IL-6, IL-10, IL-18, and IFN-γ in the serum were elevated in the acute phase, similar to the cytokine pattern reported in virus-associated HLH [20][21][22]. The kinetics of the cytokines in our patient were consistent with those in previous studies that analyzed patients with pediatric HLH, suggesting that the cytokine pattern in serum of HLH cases might be similar even though the susceptibility to HLH varies depending on the pathogen.…”

Section: Discussionsupporting

confidence: 89%

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

et al. 2020

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Background: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). Case presentation: An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. Conclusions: It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

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Section: Discussionsupporting

confidence: 89%

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

et al. 2020

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“…42 The pattern of inflammatory cytokines (elevated levels of interferon-g [IFN-g] and IL-10, with only modestly elevated IL-6 levels) has high diagnostic accuracy for sHLH and may be a useful approach to differentiate HLH from infection and to monitor patients; however, the utility of this pattern of changes needs to be verified in children and adults outside of China. [43][44][45] For diagnosis using functional assessment of cytotoxicity and genetics, see Statement 4.…”

Section: Other Diagnostic Toolsmentioning

confidence: 99%

Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

Rosée

Horne

Hines

et al. 2019

Blood

734

713

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Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome induced by aberrantly activated macrophages and cytotoxic T cells. The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults. Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory/autoimmune disorders, in which case it is called macrophage activation syndrome (MAS; or MAS-HLH). Most information on the diagnosis and treatment of HLH comes from the pediatric literature. Although helpful in some adult cases, this raises several challenges. For example, the HLH-2004 diagnostic criteria developed for children are commonly applied but are not validated for adults. Another challenge in HLH diagnosis is that patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome. Treatment algorithms targeting hyperinflammation are frequently based on pediatric protocols, such as HLH-94 and HLH-2004, which may result in overtreatment and unnecessary toxicity in adults. Therefore, dose reductions, individualized tailoring of treatment duration, and an age-dependent modified diagnostic approach are to be considered. Here, we present expert opinions derived from an interdisciplinary working group on adult HLH, sponsored by the Histiocyte Society, to facilitate knowledge transfer between physicians caring for pediatric and adult patients with HLH, with the aim to improve the outcome for adult patients affected by HLH.

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“…Cytokine imbalance also exists in patients infected with EBV. Recently, significantly higher serum concentrations of IFN-γ, TNF-α, and IL-6 were found in chronic active Epstein-Barr virus infection (CAEBV) patients [10]. EBV infection is an important factor influencing the incidence of graft-versus-host disease (GVHD) in SAA patients receiving allogeneic hematopoietic stem-cell transplantation (allo-HSTC) treatment.…”

Section: Introductionmentioning

confidence: 99%

T-lymphocyte subsets and Th1/Th2 cytokines in convalescent patients with Epstein–Barr virus-associated aplastic anemia

Chen

Bao

et al. 2019

Hematology

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Objective: The aim of this study was to analyze T-lymphocyte subsets and Th1/Th2 cytokines in convalescent patients with Epstein-Barr virus (EBV)-associated aplastic anemia (AA). Methods: Sixty AA patients were enrolled, who were in remission following immunosuppressive therapy, including 34 EBV-negative cases and 26 EBV-positive cases. Their complete blood count (CBC), T-lymphocyte subsets, Th1/Th2 cytokines were analyzed. The correlation between EBV-DNA and T-lymphocyte subsets was evaluated, as well as the relationship between EBV-DNA and Th1/Th2 cytokines. The presence of EBV-DNA in peripheral blood mononuclear cells (PBMCs) was also assessed in 60 normal controls. Results: EBV-DNA was detected in 26/60 (43.33%) patients and 21/60 (35.00%) controls. EBV-DNA copy number in AA patients was higher than in controls (Z = −2.138, P = 0.033). The percentage of CD3 + CD4 + T-lymphocytes and the ratio of CD4 + /CD8 + T-lymphocytes in the EBV-negative group were higher than in the EBV-positive group (P = 0.001 and 0.001, respectively). EBV was positively correlated with CD3 + CD8 + T-lymphocyte percentages (Pearson R: 0.496, P = 0.009). Moreover, EBV was positively correlated with IL-10 and IFN-γ levels (Pearson R: 0.559, P = 0.002 and Pearson R: 0.621, P = 0.001, respectively). Conclusions: EBV-DNA copy number in AA patients was higher than in normal controls. Both AA and EBV infection may cause changes in the levels of T-lymphocyte subsets. We recommend monitoring the changes in the immune function and EBV infection simultaneously in AA patients, especially following immunosuppressive therapy.

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Cytokine profiles as novel diagnostic markers of Epstein-Barr virus–associated hemophagocytic lymphohistiocytosis in children

Cited by 35 publications

References 27 publications

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

Recommendations for the management of hemophagocytic lymphohistiocytosis in adults

T-lymphocyte subsets and Th1/Th2 cytokines in convalescent patients with Epstein–Barr virus-associated aplastic anemia

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