Reflection and Reaction

Birth order, infection in early life, and multiple sclerosis

The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men. The rapid epidemiological changes suggest that environmental factors may modify the risk of MS.

To investigate whether occupational, physical, or social environmental influence the risk of MS differently in women than in men.

The cohort consists of all 1403 patients (939 women, 464 men) identified through Danish Multiple Sclerosis Registry aged 1–55 of years at clinical onset between 2000 and 2004, and up to 25 control persons for each case, matched by sex, year of birth and residential municipality. The same cohort was previously used to investigate the influence of the reproductive factors on the risk of MS.

By linkage to Danish population registers we found a slight albeit statistically significant excess for 6 female MS patients who had been employed in agriculture: OR 3.52; 95% CI 1.38–9.00, p=0.008 (0.046 when corrected for multiple significance) and a trend for exposure to outdoor work in 12 : OR 1.94, 95% CI 1.06–3.55, p=0.03 (0.09 when corrected for multiple significance), but the numbers of cases were small, and the effects were not found in men. Educational level, housing conditions in youth, or the presence of children unrelated by blood in the household did not influence the risk of MS.

Our study did not reveal any additional factors beyond the previously published childbirths which could explain the extent of the MS incidence increase in women.

Multiple sclerosis (MS) is considered an immune‐mediated disorder in which immune cells cross the blood–brain barrier to enter the central nervous system (CNS) wherein they augment the neuropathology of the disease. This chapter discusses the role of various immune cell types that contribute to the development and progression of MS. Specifically, the role of T cells, antigen‐presenting cells, and components of the innate immune system such as macrophages, B cells, and the complement system are discussed. The involvement of CNS‐specific cells such as microglia, astrocytes, and neurons in MS are discussed and the immunosuppressive role of regulatory T cells is considered. We introduce the involvement of chemokines and matrix metalloproteinases which helps recruit immune cells into the CNS in MS. Although the causes of MS are unknown, various factors such as genetic influences, environmental effects, and involvement of infectious agents as potential contributors to MS immune dysfunctions are also considered. With this background, we discuss the mechanisms of the immunomodulators that are used to treat MS.