ABSTRACT
Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.
Subject(s)
Autoantibodies/physiology , Multiple Sclerosis/diagnosis , Multiple Sclerosis/immunology , Myelin Sheath/immunology , Nerve Tissue Proteins/immunology , Transcription Factors/immunology , Acute Disease , Adolescent , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Child , Child, Preschool , Female , Humans , Infant , Male , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Myelin Basic Protein , Nerve Tissue Proteins/blood , Nerve Tissue Proteins/cerebrospinal fluid , Risk Factors , Syndrome , Transcription Factors/blood , Transcription Factors/cerebrospinal fluid , Young AdultABSTRACT
Oral prednisone (1)might be a convenient, inexpensive alternative to IV methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the concentration-time curve (AUC), the main component of bioavailability, did not differ between groups (p = 0.122). This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses.
Subject(s)
Anti-Inflammatory Agents/pharmacokinetics , Immunosuppressive Agents/pharmacokinetics , Methylprednisolone Hemisuccinate/pharmacokinetics , Multiple Sclerosis/drug therapy , Prednisone/pharmacokinetics , Administration, Oral , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Area Under Curve , Biological Availability , Biotransformation , Female , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Infusions, Intravenous , Liver/metabolism , Male , Methylprednisolone/blood , Methylprednisolone Hemisuccinate/administration & dosage , Methylprednisolone Hemisuccinate/therapeutic use , Middle Aged , Multiple Sclerosis/metabolism , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/metabolism , Prednisolone/blood , Prednisone/administration & dosage , Prednisone/blood , Prednisone/therapeutic useABSTRACT
OBJECTIVE: To assess the effects of glatiramer acetate and beta interferon on fatigue in multiple sclerosis. METHODS: Fatigue was measured at baseline and six months using the fatigue impact scale (FIS). Groups (glatiramer acetate and beta interferon) were evaluated for the proportion improved, using Fisher's exact test. Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables. RESULTS: Six month paired FIS assessments were available for 218 patients (76% female). Ages ranged between 19 and 61 years, with 86% having relapsing-remitting disease. Glatiramer acetate was used by 61% and beta interferon by 39%. At baseline, total FIS and subscale scores were comparable in the two groups. More patients improved on glatiramer acetate than on beta interferon on total FIS (24.8% v 12.9%, p = 0.033; adjusted odds ratio = 2.36, 95% confidence interval 1.03 to 5.42), and on physical (28.6% v 14.1%, p = 0.013) and cognitive subscales (21.1% v 10.6%, p = 0.045). Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue, after accounting for baseline group differences. CONCLUSIONS: The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with beta interferon. Confirmation of this result is required.
