TY - JOUR
T1 - Therapeutic down-regulation of central and peripheral B-cell-activating factor (BAFF) production in pediatric opsoclonus-myoclonus syndrome
AU - Pranzatelli, Michael R.
AU - Tate, Elizabeth D.
AU - Hoefgen, Erik R.
AU - Swan, Jennifer A.
AU - Colliver, Jerry A.
N1 - Funding Information:
This study was supported by grants to M.R.P. from the Chicago Institute of Neurosurgery and Neuroresearch (CINN) Foundation (Chicago, IL), the William E. McElroy Charitable Foundation (Springfield, IL), the Spastic Paralysis and Allied Diseases of the Central Nervous System Research Foundation (Illinois-Eastern Iowa District, Kiwanis International), Ronald McDonald House Charities (Central Illinois), Questcor Pharmaceuticals (Union City, CA), and donations from parents and their families. We thank Joanne Hunter and Peggy Bloomfield, as well as Adam and Donna Turtle, for their remarkable recruitment of healthy children to provide control serum samples, Dr. Donald S. Torry for use of the microplate reader, and Dr. Andrzej Bartke for use of the ELISA washer, Tammy A. Boyd for typing the manuscript, all referring physicians, and participating children and their families. We appreciate Miracle Flights for Kids (Green Valley, NV) and Air Charity Network (formerly known as Angel Flight America) (Addison, TX) for flying indigent families to our center, Ronald McDonald House for so willingly giving our families food and lodging during their stay with us, and the services of the anesthesia departments at Memorial Medical Center and St. John’s Hospital.
PY - 2008/10
Y1 - 2008/10
N2 - Opsoclonus-myoclonus syndrome (OMS) is an autoimmune, paraneoplastic, central nervous system disorder, characterized by cerebrospinal fluid (CSF) B-cell expansion and various putative autoantibodies. To investigate the role of B-cell activating factor (BAFF) in OMS and the effect of disease-modifying immunotherapies used to treat it, BAFF was measured by enzyme-linked immunoadsorbent assay in the CSF and serum of 161 children with OMS and 116 pediatric controls. The mean concentration of CSF BAFF and the CSF/serum BAFF ratio were significantly higher in untreated OMS compared to neurological controls. CSF and serum BAFF levels were significantly lower in children treated with ACTH or corticosteroids, as was the CSF/serum BAFF ratio. There was a strong, negative correlation between CSF or serum BAFF levels and ACTH dose. Monthly IVIg infusions had no net impact on BAFF levels, and the combination of IVIg with ACTH or steroids did not reduce or enhance their anti-BAFF effects. These data indicate that BAFF production is increased centrally, not peripherally, in OMS, implying astrocytic over production. The novel dose-related central and peripheral anti-BAFF properties of ACTH, especially, have implications for other BAFF-related autoimmune disorders, infectious diseases, and cancers.
AB - Opsoclonus-myoclonus syndrome (OMS) is an autoimmune, paraneoplastic, central nervous system disorder, characterized by cerebrospinal fluid (CSF) B-cell expansion and various putative autoantibodies. To investigate the role of B-cell activating factor (BAFF) in OMS and the effect of disease-modifying immunotherapies used to treat it, BAFF was measured by enzyme-linked immunoadsorbent assay in the CSF and serum of 161 children with OMS and 116 pediatric controls. The mean concentration of CSF BAFF and the CSF/serum BAFF ratio were significantly higher in untreated OMS compared to neurological controls. CSF and serum BAFF levels were significantly lower in children treated with ACTH or corticosteroids, as was the CSF/serum BAFF ratio. There was a strong, negative correlation between CSF or serum BAFF levels and ACTH dose. Monthly IVIg infusions had no net impact on BAFF levels, and the combination of IVIg with ACTH or steroids did not reduce or enhance their anti-BAFF effects. These data indicate that BAFF production is increased centrally, not peripherally, in OMS, implying astrocytic over production. The novel dose-related central and peripheral anti-BAFF properties of ACTH, especially, have implications for other BAFF-related autoimmune disorders, infectious diseases, and cancers.
KW - Ataxia
KW - Cerebrospinal fluid
KW - Corticotropin
KW - Neuroblastoma
KW - Paraneoplastic syndrome
UR - http://www.scopus.com/inward/record.url?scp=53149103899&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2008.06.001
DO - 10.1016/j.cyto.2008.06.001
M3 - Article
C2 - 18675552
AN - SCOPUS:53149103899
VL - 44
SP - 26
EP - 32
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 1
ER -