J. J F Oger

Immunogenetics of multiple sclerosis

Publisher Summary This chapter discusses the genetic aspects of multiple sclerosis. Multiple sclerosis is an inflammatory demyelinating disease of unknown cause. Current opinion holds that multiple sclerosis will likely prove to be an autoimmune process, an infectious disease, or some combination of the two. Several lines of evidence buttress this opinion, but all the evidence is indirect. Certain facts have been established in multiple sclerosis that are consistent with an autoimmune or infectious basis for the disease, and these facts ultimately will have to be incorporated into any coherent theory of its pathogenesis. The chapter presents data obtained in family studies that indicate that concordance for multiple sclerosis in monozygotic twins exceeds that in dizygotic twins. On the basis of the analysis of the family studies of multiple sclerosis conducted to date, researchers are able to draw only a few conclusions based on these data alone. Concordance for multiple sclerosis in monozygotic twins does not exceed 25% and is probably lower. This finding proves that genetic endowment alone does not suffice for multiple sclerosis. Moreover, studies of HLA in multiple sclerosis siblings concordant for multiple sclerosis reveals more shared haplotypes than chance would predict. This finding argues yet again that HLA endowment is a major determinant of susceptibility to multiple sclerosis.

A new solid-phase radioimmunoassay to measure IgG secreted by cultured human lymphocytes

We describe a simple solid-phase radioimmunoassay (RIA) to detect IgG based on competitive binding between radiolabeled and unlabeled IgG for anti-IgG antibody physically adsorbed to the wells of polyvinyl microtiter plates. The assay is sensitive (1 ng), rapid, and is particularly suited for studies of in vitro IgG secretion by human peripheral blood lymphocytes, since such studies require large numbers of cultures. Conditions which permit measurement, by means of this assay, of helper and suppressor T cell effects on IgG production by human B cells in culture are described.

Neutralizing antibodies to poliovirus and mumps virus in amyotrophic lateral sclerosis.

Abstract Neutralizing (Nt) antibodies to poliovirus types 1, 2 and 3, and to mumps virus, were measured in sera from 27 patients with amyotrophic lateral sclerosis, and from 28 age- and sex-matched controls. No significant differences were observed in distribution or in geometric mean titers of antibodies, when the two groups were compared.

Modulation of T lymphocyte differentiation antigens: Influence of aging

In vitro modulation of human T lymphocyte surface differentiation antigens T3, T8, and T4, by their respective monoclonal antibodies, was studied as a function of donor age. Kinetic studies performed on lymphocytes from young adults indicated that modulation is dependent on concentration of antibody used and duration of culture. OKT3 modulates T3 rapidly (maximum at less than 24 hr) and relatively completely (79% at the highest concentration of antibody used). By 48 hr, regeneration of the T3 antigen is apparent. T8 modulation by OKT8 is slower (continued modulation at 48 hr) and less complete than is T3 modulation by OKT3. OKT4 does not modulate the T4 antigen. In elderly individuals modulation of T3 by OKT3 is preserved whereas modulation of T8 by OKT8 is significantly reduced (24 +/- 8% at 48 hr vs 53 +/- 4% for young controls). These observations document further age-related changes in properties of human T suppressor cells.

Immunogenetics of neurological diseases

Abstract In this article Joel Oger and Barry Arnason outline the relationships between immunology and genetics as they describe the histocompatibility system. They then continue to describe irregularities in the histocompatability system which occur in various neurological diseases, with special reference to multiple sclerosis, myasthenia gravis, and amyotrophic lateral sclerosis.

Studies of Immune Regulation in MS using Monoclonal Antibodies against T Cell Subsets

AbstractWe have studied immune regulation in MS using monoclonal antibodies against T cell subsets.We could confirm a decrease in the number of T suppressor cells in peripheral blood of 16 active MS patients (16.7%±1.7) when compared to 16 healthy controls (26.2±2.2 p