Objective. Immunization with peptide fragments of autoantigens may lead to an immune response at both the T and B cell level that is directed not only at the immunogen, but also at the autoantigen from which the peptide came. In addition, a complex multicomponent particle may become the target of this expanded immune response. The purpose of this study was to determine the ability of several different peptides from 60-kd Ro to induce expansion of the immune response to the Ro/La RNP particle.Methods. We immunized BALB/c mice with 3 different oligopeptides from human 60-kd Ro (or, SSA).Results. Animals immunized with peptides either identical to or differing by only 1 amino acid developed autoimmunity to the entire Ro RNP particle. Animals immunized with a human peptide highly divergent from the corresponding mouse sequence developed an immune response to the immunogen only and showed little evidence of epitope spreading. Furthermore, these mice did not have antibodies that bound the poorly conserved mouse homolog peptide, and the antibody response to this peptide did not include IgG1. Conclusion.These data indicate that B lymphocytes specific for the self-peptide that is homologous to the immunogen are a critical determinant for spreading of the immune response to other components of self.

Rituximab, a monoclonal antibody to CD20, is an effective treatment for relapsing remitting multiple sclerosis (MS) reducing relapse rate by at least 50% over time. Although the mechanism for this clinical benefit is unclear, rituximab depletes circulating B cells, which can perform antigen presentation and stimulation of T cells. Another anti-CD20 drug, ocrelizumab, has recently been FDA approved to treat both relapsing remitting and progressive forms of MS. While long-term effects of ocrelizumab use are essentially unknown, long-term use of rituximab has been associated with the development of progressive multifocal leukoencephalopathy (PML) at an incidence of approximately 1/25,000 in non-MS conditions. Serostatus for JC virus (JCV), the causative agent for PML, is an important risk stratification tool for natalizumab, but its utility in other MS treatments is uncertain. We found that rituximab use was associated with a reduction in JCV antibody index values in MS patients. Reductions in immunoglobulins, IgM in particular, are seen in concert with JCV antibody reductions. Physicians should exercise caution when using JCV antibody indices to assess any risk of PML for patients on rituximab.

Background and ObjectivesWe sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic.MethodsA pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization.ResultsOur cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support.DiscussionThe case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.