High levels of plasma interleukin-17A are associated with severe neurological sequelae in Langerhans cell histiocytosis.

OBJECTIVE:Langerhans cell histiocytosis (LCH) is a granulomatous inflammatory myeloid neoplasia associated with a cytokine storm in both serum and lesions. Increased levels of plasma interleukin-17A (IL-17A) in LCH patients have been reported, but this finding was not confirmed in all studies. Neurodegeneration is a devastating complication of LCH (ND-LCH). We aimed to revisit the issue of plasma IL-17A levels in LCH, by using a larger number of patients, and also to investigate the relationship between IL-17A and LCH sequelae, especially ND-LCH. METHODS:Plasma samples from 68 LCH patients and 127 controls were analyzed for IL-17A levels by two ELISAs with different anti-IL-17A capture antibodies: either polyclonal or neutralizing monoclonal antibodies in 17polyAb-ELISA or 17mAb-ELISA, respectively. RESULTS:Both ELISAs had a similar capacity to specifically detect recombinant or native human IL-17A, as well as plasma IL-17A from LCH patients. We confirmed the finding of higher levels of plasma IL-17A in LCH patients compared to controls (p < 0.0001). The association of IL-17A with LCH was independent of the ELISA used, and of gender, age, disease class activity, and pattern of tissue-organ involvement (single-system versus multi-system). ROC analyses (p < 0.0001) allow to discriminate LCH patients from the control group, supporting the notion that IL-17A may be a potential biomarker for LCH. More interestingly, high IL-17A levels were significantly associated with LCH patients having sequelae, with the highest plasma levels in patients with ND-LCH (p < 0.0001). CONCLUSION:The association between high levels of IL-17A and LCH was confirmed. IL-17A may be associated with ND-LCH development. This might have therapeutic implications, offering a novel target for precision therapy of ND-LCH.