Biomarker and morphological characteristics of Epstein‐Barr virus‐related hemophagocytic lymphohistiocytosis

Abstract

Background. Viruses may induce primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), but it may not be possible to discriminate between these two in patients with a negative family history. Among these HLH cases, fulminant and fatal virus-associated hemophagocytic syndrome (VAHS) occurs mostly in relation to Epstein-Barr virus (EBV) infection. Although the immunological characteristics of EB-VAHS were previously reported, data on non-EB-VAHS were sporadic and fragmentary. This study has compared the clearly distinguishable groups of EBV-positive vs. EBVnegative HLH cases. Procedure. Among 26 patients with EBV-related HLH and 12 patients with non-EBV HLH, peripheral blood mononuclear cell (PBMC) subsets and serum concentrations of cytokines at the active phase of the disease were compared. Blood and bone marrow smears were also compared. Results and Conclusions. The frequency of the CD3 + HLADR + subset in PBMC (median 34.3% vs. 4.8%), of serum concentrations of interferon (IFN)-␥ (median 105 U/ml vs. 2.4 U/ml), and of soluble interleukin-2-receptor (sIL-2R) (median 14,700 U/ml vs. 3,412 U/ml) were significantly different between these two groups. Morphological characteristics were noted for EBVrelated HLH cases. Mortality also differed between these two groups, 9/26 vs. 0/12 (P = 0.05). Data indicate pronounced immunological imbalance and poor prognosis in EBVrelated HLH cases. These parameters could be useful for determining an EBV involvement as well as risk factors in the early care and treatment of HLH patients. Med. Pediatr. Oncol. 31: 131-137, 1998.

High levels of IL-10 and determination of other cytokines and chemokines in HIV-associated haemophagocytic syndrome

“…The starting point of this study was that both HPS and HIV infection are cytokine diseases, that are associated with high levels of cytokines in the patients' sera and plasma. As expected, the levels of IFN-g [2,7,8,10,12,17,18] and IL-10 [10] were higher in the plasma of the HPS patient than in that of the control patients, as previously reported. However, MIP-1b levels were also higher, and that has never been reported before.…”

Infections associated with haemophagocytic syndrome

“…In EBV-associated haemophagocytic syndrome, EBV infects primary CD8+ cells 30 with a failure to produce a suffi cient number of EBV-specifi c cytotoxic T cells, suggesting a NK T-cell dysfunction. 31 The typical cytokine storm seen in haemophagocytic syndrome is more pronounced in EBV-associated disease, 32 causing haemophagocytosis and organ dysfunction.…”

Debate around infection-dependent hemophagocytic syndrome in paediatrics

“…The distinction between the monoclonal proliferation of T lymphocytes seen in EBV-related HPS and EBV-positive T cell lymphomas may describe the extremes of a spectrum of disordered T lymphocyte proliferation following EBV infection. The inflammatory cytokine over-production seen in patients with EBV-related HPS tends to be much more pronounced than that observed in patients with other forms of HPS [35]. Of all of the infections associated with HPS, EBV infection has the worst prognosis in the presence of underlying hereditary disorders, diffuse intravascular coagulation, neutropenia, or central nervous system involvement [36].…”