IL-17A in LCH: Systemic Biomarker, Local Factor, or None of the Above?

Abstract

Langerhans cell histiocytosis (LCH) is an enigmatic disease characterized by the infiltration of monocytes, macrophages, and dendritic cells, including Langerhans cells, into affected tissues. These immune cells traffic aberrantly, leaving inflammatory sequelae, organ dysfunction, endocrine deficits, and in rare cases a devastating neurodegenerative process in their wake. There remains much to learn about LCH, as debate persists as to whether it is a reactive disease of deregulated immune function or a bona fide neoplastic process; moreover, a molecular understanding of its pathobiology is lacking. Therefore, the finding from the Delprat group that interleukin (IL)-17A is elevated in the serum of LCH patients and may be involved in its pathogenesis was very welcome.1 However, in this issue, Peters et al. report that they have been unable to validate this finding, having failed to identify IL-17A at either the RNA or the protein level in a large number of LCH lesions.2 Just as independent validation of a novel biological finding is of principal importance in its garnering acceptance, so too should we value conflicting data and try to understand the discrepancies at hand.