Acute-phase ITIH4 levels distinguish multi-system from single-system Langerhans cell histiocytosis via plasma peptidomics

Table 1 Clinical manifestations, treatment, outcome and proposed relationship between LCH classification, MCPyV and ITIH4 based on both our and others’ data

Classification			Prevalence (approximate)	Clinical manifestaions	Treatment	Outcome	MCPyV-DNA		Mutations		ITIH4
Present		Former					PBMC	LCH tissue	PBMC	LCH tissue	Plasma
LCH-RO (+)	MS^a	Letterer–Siwe disease	10 %	Serious anemia, Thrombocytopenia	Multi-agent chemotherapy and Salvage therapy	Mortality rates: 16–38 %	+	NA	+	+	NA
LCH-RO (−)	MS	Hand–Schüller–Christian disease	20 %	Bone pain, Skin rash	Multi-agent chemotherapy	Excellent survival rate	-	+	-	+	high
LCH-RO (−)	SS	Eosinophilic granuloma	70 %	Asymptomatic or Bone pain	Wait-and-see strategy^b or Chemotherapy	Excellent prognosis		+		+	low

ITIH4 inter-alpha-trypsin inhibitor heavy chain 4, LCH Langerhans cell histiocytosis, LCH-RO (+) LCH with involvement of at least one high-risk organ (spleen, liver, and bone marrow), LCH-RO (−) LCH with no involvement of high-risk organ, MCPyV Merkel cell polyomavirus, MS-LCH multisystem LCH, SS-LCH single-system LCH, NA not available
^aNearly all LCH-risk organ (RO) (+) type is MS-LCH-RO (+), although SS-LCH-RO (+) type has been reported [15, 16]
^bLocalized LCH may resolve spontaneously [2], which might be related to oncogene-induced senescence [45] relayed by interleukin-dependent inflammatory network [46]. We detected MCPyV-DNA in the peripheral blood mononuclear cells (PBMC) of patients with LCH-RO (+) but not those with LCH-RO (−); this difference was significant. In patients with LCH-RO (−), MCPyV-DNA sequences were present in LCH tissues

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