Exposure to Infant Siblings During Early Life and Risk of Multiple Sclerosis

Abstract

The “hygiene hypothesis” proposes that early life infections may down-regulate allergic and autoimmune disorders.¹ Having siblings may increase the number of early life infections. In fact, lack of contact with siblings has been associated with T_H2-related immune disorders and some T_H1-related disorders. For multiple sclerosis (MS), a T_H1-related autoimmune disease, the association with birth order has been inconsistent across studies^2-4 and absent in others.^5-7 However, birth order provides clearer information on the number of older siblings, and the independent influence of younger siblings has not been evaluated. Younger siblings may be important because infants provide a source of common viral infections. Reexposure to active viral infection is known to cause immune boosting with rising IgG titers in seropositive individuals.⁸ Also, repeated antigenic stimulation induces affinity maturation of the B-cell line⁹ and influences T-cell phenotype¹⁰ and T-cell receptor diversity.¹¹ This may be advantageous if the acquisition of a highly developed immune response to putative viral triggers is required to prevent MS development in later life.