Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma‐associated hemophagocytic lymphohistiocytosis

Abstract

Summary Lymphoma‐associated haemophagocytic lymphohistiocytosis (L‐HLH) is characterized by excessively activated macrophages and cytotoxic T lymphocytes, but few reliable markers for activated macrophages are available clinically. This study, designed to discover novel biomarkers for the diagnosis of lymphoma patients with L‐HLH, was initiated between 2016 and 2018. Fifty‐seven adult lymphoma patients were enrolled — 39 without HLH and 18 with HLH. The differential serum protein expression profile was first screened between lymphoma patients with and without L‐HLH by a quantitative mass spectrometric approach. Soluble V‐set and immunoglobulin domain‐containing 4 (sVSIG4), specifically expressed by macrophages, was significantly upregulated in the L‐HLH group. Subsequently, sVSIG4 concentration was confirmed by enzyme‐linked immunosorbent assay to be significantly increased in lymphoma patients with L‐HLH. When it was exploited for the diagnosis of lymphoma patients with L‐HLH, the area under a receiver operating characteristic curve was 0·98 with an optimal cut‐off point of 2195 pg/ml and the corresponding sensitivity and specificity were 94·44% and 94·87% respectively. In addition, the one‐year overall survival was significantly worse in patients with a sVSIG4 concentration above 2195 pg/ml compared with those below 2195 pg/ml (5·3% vs. 72·2%, P < 0·0001). sVSIG4 may be a surrogate marker of activated macrophages for the diagnosis of lymphoma patients with L‐HLH.

Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction

“…We investigated whether IFNγ, CXCL9, and other markers associated with MAS could distinguish different SARS-CoV-2 outcomes (Fig. 4a ) 28 , 30 , 31 . Unsupervised hierarchical clustering showed two distinct groups of MIS-C patients that had elevations in most MAS markers.…”

Image‐guided core needle biopsy as the first‐line diagnostic approach in lymphoproliferative disorders—A review of the current literature

“…These biomarkers may have the potential to aid clinical diagnosis. For instance, diagnostic markers in blood or cerebrospinal fluid (CSF) such as CXCL‐13, beta‐2‐microglobulin and neopterin could facilitate early diagnosis of CNS lymphoma 23 and sVSIG4 may be a surrogate marker of activated macrophages for the diagnosis of lymphoma patients with lymphoma‐associated haemophagocytic lymphohistiocytosis (L‐HLH) 24 . Although non‐invasive biomarkers are clearly no substitute for tissue, they can help aid the diagnostic process, particularly in diseases that notoriously elude diagnosis, such as intravascular B‐cell lymphoma 25 …”

Immunomodulatory receptor VSIG4 is released during spontaneous bacterial peritonitis and predicts short-term mortality

“… 21 In addition to its role in bacterial clearance, VSIG4 limits excessive inflammation from classically activated macrophages 22 and suppresses cytokine production by T cells. 23 Soluble VSIG4 (sVSIG4), which is released under conditions of tissue macrophage activation, 24 inhibits complement activation through the alternative pathway. 25 , 26 …”