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.
Type de document :
Article dans une revue
Clinical Proteomics, BioMed Central, 2015, 12 (1), pp.16. 〈10.1186/s12014-015-9089-2〉
Liste complète des métadonnées

Littérature citée [43 références]  Voir  Masquer  Télécharger
Contributeur : Mireille Bos <>
Soumis le : mardi 30 juin 2015 - 16:34:20
Dernière modification le : jeudi 11 janvier 2018 - 06:23:10
Document(s) archivé(s) le : mardi 25 avril 2017 - 20:34:05


Fichiers éditeurs autorisés sur une archive ouverte




Ichiro Murakami, Yukiko Oh, Akira Morimoto, Hitoshi Sano, Susumu Kanzaki, et al.. Acute-phase ITIH4 levels distinguish multi-system from single-system Langerhans cell histiocytosis via plasma peptidomics. Clinical Proteomics, BioMed Central, 2015, 12 (1), pp.16. 〈10.1186/s12014-015-9089-2〉. 〈inserm-01170002〉



Consultations de la notice


Téléchargements de fichiers