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Journal of Clinical Immunology

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01-05-2013 | Original Research

CCR4 Agonists CCL22 and CCL17 are Elevated in Pediatric OMS Sera: Rapid and Selective Down-Regulation of CCL22 by ACTH or Corticosteroids

Authors: Michael R. Pranzatelli, Elizabeth D. Tate, Nathan R. McGee, Jerry A. Colliver, Richard M. Ransohoff

Published in: Journal of Clinical Immunology | Issue 4/2013

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.

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Title: CCR4 Agonists CCL22 and CCL17 are Elevated in Pediatric OMS Sera: Rapid and Selective Down-Regulation of CCL22 by ACTH or Corticosteroids
Authors: Michael R. Pranzatelli
Elizabeth D. Tate
Nathan R. McGee
Jerry A. Colliver
Richard M. Ransohoff
Publication date: 01-05-2013
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 4/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-013-9867-4

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Abstract

Purpose

Methods

Results

Conclusions

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