Clinical and experimental immunology 2017 07 15() doi 10.1111/cei.13015
The purpose was to evaluate the capacity of 6-mercaptopurine (6-MP), a known immunosuppressant, to normalize cerebrospinal fluid (CSF) lymphocyte frequencies in opsoclonus-myoclonus syndrome (OMS) and function as a steroid sparer. CSF and blood lymphocytes were immunophenotyped in 11 children with OMS (without CSF B cell expansion), using a comprehensive panel of cell surface adhesion, activation, and maturation markers by flow cytometry, and referenced to 18 pediatric controls. Drug metabolites, lymphocyte counts, and liver function tests were used clinically to monitoring therapeutic range and toxicity. In CSF, adjunctive oral 6-MP was associated with a 21% increase in the low percentage of CD4(+) T-cells in OMS, restoring the CD4/CD8 ratio. The percentage of CD4(+) T-cells that were IFN-γ(+) was reduced by 66%, shifting the cytokine balance away from Th1 (proinflammatory) predominance. The percentage of NK cells decreased significantly in CSF (-32%) and blood (-67 to -82%). Low blood absolute lymphocyte count was more predictive of improvement in CSF lymphocyte proportions (correlated with % CD4(+) T cells) than the 6-thioguanine level (no correlation). 6-MP was difficult to titrate: 50% achieved the target absolute lymphocyte count (<1.5 K/mm); 20%, the 'therapeutic' 6-thioguanine level; and 40% the non-toxic 6-methylmercaptopurine level. Side effects and transaminase elevation were mild and reversible. Clinical steroid-sparing properties and lowered relapse frequency were demonstrated. 6-MP displayed unique pharmacodynamic properties that may be useful in OMS and other autoimmune disorders. Its steroid sparer capacity is limited to children in whom the therapeutic window can be reached without limiting pharmacokinetic factors or side effects. This article is protected by copyright. All rights reserved.