Objective To evaluate whether B-cell depletion before enzyme replacement therapy (ERT) initiation can block acid alpha-glucosidase (GAA) antibody responses and improve clinical outcomes. Study design ...Six subjects with Pompe disease (including 4 cross-reacting immunologic material–negative infants) aged 2-8 months received rituximab and sirolimus or mycophenolate before ERT. Four subjects continued to receive sirolimus, rituximab every 12 weeks, and intravenous immunoglobulin monthly for the duration of ERT. Sirolimus trough levels, IgG, CD3, CD4, CD8, CD19, CD20, N-terminal pro-brain natriuretic peptide, creatine kinase, creatine kinase-MB, C-reactive protein, platelets, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase were measured regularly. Results Immunomodulation achieved B-cell depletion without adverse effects. After 17-36 months of rituximab, sirolimus and ERT, all subjects lacked antibodies against GAA, 4 continued to gain motor milestones, yet 2 progressed to require invasive ventilation. The absence of infusion-associated reactions allowed the use of accelerated infusion rates. Conclusion B-cell depletion and T-cell immunomodulation in infants naïve to ERT was accomplished safely and eliminated immune responses against GAA, thereby optimizing clinical outcome; however, this approach did not necessarily influence sustained independent ventilation. Importantly, study outcomes support the initiation of immunomodulation before starting ERT, because the study regimen allowed for prompt initiation of treatment.
An Unusual Cause of Neonatal Meningitis Udassi, Sharda, MD; Udassi, Jai P., MD; Giordano, Beverly P., MS, RN, CPNP, PMHS ...
Journal of pediatric health care,
11/2015, Volume:
29, Issue:
6
Journal Article
Infants were immunized by aerosol (103.6 plaque-forming units pfu/dose) or subcutaneous (sc) (104.27 pfu/dose) administration of Edmonston-Zagreb measles vaccine. Measles-specific T cell ...proliferative responses with a stimulation index of ⩾3 developed in 72% of children given aerosol-administered vaccine, compared with 87% given sc-administered vaccine (P = .06). Seroconversion rates were 90% after aerosol-administered vaccine and 100% after sc-administered vaccine (P=.01), and measles geometric mean titers were 237 milli–international units (mIU) (95% confidence interval CI, 146–385 mIU) and 487 mIU (95% CI, 390–609 mIU) in each group, respectively (P=.01). Measles-specific T and B cell responses were weaker after aerosol than after sc vaccination, indicating a need to use a higher aerosol dose to achieve optimal immunogenicity
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