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Immunophenotype of Blood Lymphocytes in Neuroblastoma-Associated Opsoclonus-Myoclonus

Objective: To determine whether the distribution of peripheral blood mononuclear cells (PBMCs) is altered in paraneoplastic opsoclonus-myoclonus (POM). Methods: PBMCs from 17 children with POM, 17 children with OM but no tumor, and 17 controls were immunophenotyped using a comprehensive panel of surface markers by dual-laser flow cytometry. All groups were matched for age and gender; POM and OM patients were matched for treatment. Results: In the POM patients, the CD4+ T-cell subset was smaller in both relative size (−18%, P = 0.02) and absolute size (−41%, P = 0.03) compared with controls. The CD4/CD8 ratio also was less (−29% to −44%) and was related to POM duration (P = 0.03). The absolute but not relative size of the γδ T-cell subset was reduced (−44%, P = 0.02). There were no significant abnormalities of CD19+ B-cells, CD3− or CD3+ NK cells, HLA-DR+ or CD25+ T-cells, or CD45RA+ or CD45RO+ T-cells. Prior tumor chemotherapy, which was associated with a higher percentage but not number of CD8+ T-cells, did not restore the CD4+ T-cell subset. When the POM and OM groups, which were not significantly different, were combined, chemotherapy decreased both the relative and absolute size of the CD19+ B-cell pool and had small effects on other lymphocyte subsets. Conclusions: POM is characterized by T-cell abnormalities of PBMCs, the most robust of which is reduction of the CD4+ T-cell subset and the CD4/CD8 ratio. Although this reduction was found previously in cerebrospinal fluid in POM patients, PBMC subsets did not otherwise reflect cerebrospinal fluid abnormalities. Longitudinal studies will be necessary to determine whether PBMC abnormalities could serve as treatment markers.