Abstract |
Identifying and blocking chemokine inflammatory mediators in pediatric opsoclonus-myoclonus syndrome (OMS) is critical to the treatment of this autoimmune, paraneoplastic, neurological disorder. In a prospective, case-control, clinico-scientific study of children with OMS compared to non-inflammatory neurological controls and other inflammatory neurological disorders, CCL19 (n=369) and CCL21 (n=312) were quantified in CSF and serum, respectively, by ELISA. Both cross-sectional and longitudinal effects of OMS and various immunotherapies were evaluated. Significant upregulation of CCL21 concentration (mean ± SD) (+32%) was found in serum of untreated OMS (630 ± 133 pg/mL), compared to controls (478 ± 168 pg/mL), (p<0.0001). Both corticosteroids and ACTH ( corticotropin) significantly lowered CCL21 to control levels, as they did in combination with IVIg, rituximab, cyclophosphamide or other treatments, without additional reduction attributable to the other agents. In a pilot longitudinal study of ACTH-based triple therapy, the mean serum CCL21 concentration fell 59% from elevated to less than 1 SD below controls 1 week after high-dose ACTH, gradually returning to the control mean with ACTH tapering by 3 weeks and out to 12 weeks (p<0.0001). In contrast, CCL19, detectable in CSF, was not significantly altered by OMS or various immunotherapies. In the "high" CCL21 subgroup, higher serum concentrations of CCL22 (+57%) and CXCL13 (+40%), as well as the CSF concentration of BAFF (+64%), also were found. Elevated serum CCL21, not CSF CCL19, correlates with OMS severity and duration in pediatric OMS. Corticosteroids and ACTH were the only immunotherapies evaluated that down-regulated CCL21 production. Validation studies are needed to assess treatment biomarker status.
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Authors | Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee, Richard M Ransohoff |
Journal | Cytokine
(Cytokine)
Vol. 64
Issue 1
Pg. 331-6
(Oct 2013)
ISSN: 1096-0023 [Electronic] England |
PMID | 23764550
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Adrenal Cortex Hormones
- Antibodies, Monoclonal, Murine-Derived
- B-Cell Activating Factor
- Biomarkers
- CCL19 protein, human
- CCL21 protein, human
- CCL22 protein, human
- CCR7 protein, human
- CXCL13 protein, human
- Chemokine CCL19
- Chemokine CCL21
- Chemokine CCL22
- Chemokine CXCL13
- Immunoglobulins, Intravenous
- Immunologic Factors
- Immunosuppressive Agents
- Receptors, CCR7
- TNFSF13B protein, human
- Rituximab
- Cyclophosphamide
- Adrenocorticotropic Hormone
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Topics |
- Adolescent
- Adrenal Cortex Hormones
(metabolism, therapeutic use)
- Adrenocorticotropic Hormone
(metabolism, therapeutic use)
- Antibodies, Monoclonal, Murine-Derived
(pharmacology)
- B-Cell Activating Factor
(cerebrospinal fluid)
- Biomarkers
(blood)
- Case-Control Studies
- Chemokine CCL19
(cerebrospinal fluid)
- Chemokine CCL21
(blood, metabolism)
- Chemokine CCL22
(blood)
- Chemokine CXCL13
(blood)
- Child
- Child, Preschool
- Cross-Sectional Studies
- Cyclophosphamide
(pharmacology)
- Down-Regulation
- Female
- Humans
- Immunoglobulins, Intravenous
(pharmacology)
- Immunologic Factors
(pharmacology)
- Immunosuppressive Agents
(pharmacology)
- Immunotherapy
- Infant
- Inflammation
- Male
- Opsoclonus-Myoclonus Syndrome
(blood, drug therapy, metabolism)
- Prospective Studies
- Receptors, CCR7
(blood, metabolism)
- Rituximab
- Young Adult
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