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Journal articles
Acute-phase ITIH4 levels distinguish multi-system from single-system Langerhans cell histiocytosis via plasma peptidomics
Abstract : Background:
Langerhans cell histiocytosis (LCH) is a proliferative disorder in which abnormal Langerhans cell (LC)-like
cells (LCH cells) intermingle with inflammatory cells. Whether LCH is reactive or neoplastic remains a controversial
matter. We recently described Merkel cell polyomavirus (MCPyV) as a possible causative agent of LCH and proposed
interleukin-1 loop model: LCH is a reactive disorder with an underlying oncogenic potential and we now propose to
test this theory by looking for acute markers of inflammation. We detected MCPyV-DNA in the peripheral blood cells of
patients with high-risk organ-type (LCH-risk organ (RO) (+)) but not those with non
–
high-risk organ-type LCH (LCH-RO
(
−
)); this difference was significant. LCH-RO (
−
) is further classified by its involvement of either a single organ system
(SS-LCH) or multiple organ systems (MS-LCH). In patients with LCH-RO (
−
), MCPyV-DNA sequences were present in LCH
tissues, and significant differences were observed between LCH tissues and control tissues associated with conditions
such as dermatopathic lymphadenopathy and reactive lymphoid hyperplasia. Although MCPyV causes subclinical
infection in nearly all people and 22 % of healthy adults will harbor MCPyV in their buffy coats, circulating monocytes
could serve as MCPyV reservoirs and cause disseminated skin lesions.
Methods:
Plasma sample from 12 patients with LCH-RO (
−
) (5 MS-LCH and 7 SS-LCH) and 5 non-LCH patients were
analyzed by peptidomics. Mass spectrometry (MS) spectra were acquired and peptides exhibiting quantitative
differences between MS-LCH and SS-LCH patients were targeted.
Results:
One new candidate biomarker, m/z 3145 was selected and identified after obtaining a MS/MS fragmentation
pattern using liquid chromatography-MS/MS. This peak was identified as a proteolytic fragment derived from inter-
alpha-trypsin inhibitor heavy chain 4 (ITIH4, [PDB: Q14624]).
Conclusions:
Peptidomics of LCH have revealed that the level of
acute-phase ITIH4 distinguishes MS-LCH-RO (
−
)
from SS-LCH-RO (
−
). Acute-phase proteins serve non-specific, physiological immune functions within the innate
immune system. LCH may be a reactive disorder with both underlying neoplastic potential of antigen presenting
cells harboring
BRAF
mutations and hyper-immunity of other inflammatory cells against MCPyV infection. Among
LCH-RO (
−
), MCPyV-DNA sequences were present in both MS-LCH tissues and SS-LCH tissues without significant
differences. ITIH4 may show that LCH activity or LCH subt
ypes correlates with the systemic or localized reactions
of MCPyV infection.
Cited literature [43 references]
https://www.hal.inserm.fr/inserm-01170002
Contributor : Mireille Bos <>
Submitted on : Tuesday, June 30, 2015 - 4:34:20 PM
Last modification on : Thursday, April 9, 2020 - 11:56:43 AM
Long-term archiving on: : Tuesday, April 25, 2017 - 8:34:05 PM
Contributor : Mireille Bos <>
Submitted on : Tuesday, June 30, 2015 - 4:34:20 PM
Last modification on : Thursday, April 9, 2020 - 11:56:43 AM
Long-term archiving on: : Tuesday, April 25, 2017 - 8:34:05 PM
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