CCR4 agonists CCL22 and CCL17 are elevated in pediatric OMS sera: rapid and selective down-regulation of CCL22 by ACTH or corticosteroids

J Clin Immunol. 2013 May;33(4):817-25. doi: 10.1007/s10875-013-9867-4. Epub 2013 Jan 23.

Abstract

Purpose: To study the role of Th2-attracting chemokines in opsoclonus-myoclonus syndrome (OMS), a serious neurological paraneoplastic disorder in need of better immunological understanding and therapy.

Methods: The CCR4 agonists CCL22 and CCL17 were measured in serum by ELISA in children with OMS (238 and 260, respectively), pediatric controls (115 and 143), and other inflammatory neurological disorders (33 and 24).

Results: Both CCL22 (+55 %) and CCL17 (+121 %) were significantly elevated in untreated OMS compared to controls and inter-correlated (p < 0.0001). Their concentrations in untreated OMS also were higher than in OIND (21 %, 41 %). The concentration of CCL22 in ACTH and steroids groups (not IVIg) was 51 % lower than in controls, but only a smaller effect of ACTH on CCL17 was found. Prospective longitudinal studies revealed a precipitous 81 % drop in CCL22 even by the first week of high-dose ACTH therapy, staying below control mean for at least 12 weeks, and a 34 % reduction after 8 months of combined treatment. Response to ACTH was dose-related (r = -0.50, p < 0.0001). Luminex detection confirmed the ELISA results for CCL22, which were about 200 % higher.

Conclusions: These data reveal an elevated serum concentration of Th2-attracting chemokines CCL22 and CCL17 in OMS. Marked and rapid reduction in CCL22, not CCL17, with either ACTH or steroid therapy suggests differential regulation and cellular sources of CCR4 ligands, and CCL22 as a potential candidate biomarker for ACTH or corticosteroid effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Adrenocorticotropic Hormone / administration & dosage
  • Adrenocorticotropic Hormone / adverse effects
  • Chemokine CCL17 / blood*
  • Chemokine CCL17 / genetics
  • Chemokine CCL17 / metabolism
  • Chemokine CCL22 / blood*
  • Chemokine CCL22 / genetics
  • Chemokine CCL22 / metabolism
  • Child
  • Child, Preschool
  • Down-Regulation
  • Female
  • Humans
  • Infant
  • Male
  • Opsoclonus-Myoclonus Syndrome / blood
  • Opsoclonus-Myoclonus Syndrome / drug therapy
  • Opsoclonus-Myoclonus Syndrome / immunology*
  • Prospective Studies
  • Receptors, CCR4 / agonists
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Up-Regulation

Substances

  • Adrenal Cortex Hormones
  • CCR4 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • Receptors, CCR4
  • Adrenocorticotropic Hormone