Multiple sclerosis-associated agent: neutralization of the agent by human sera

A total of 172 sera from patients with multiple sclerosis (MS), theri relatives and nursing personnel, patients with other neurological and nonneurological diseases, and healthy donors living in the United State or East Africa under vastly divergent hygienic conditions were examined for their capacity to neutralize the MS-associated agent (MSAA), which induces in experimental animals a transitory depression of circulating polymorphonuclear leukocytes (PMN). A considerable proportion of sera from MS patients and their relatives or nursing personnel and East African donors revealed neutralizing activity, but only one of 59 sera from American donors without known contacts with MS patients revealed neutralizing activity. Some of the sera could be diluted 100- or 1,000- fold and still prevent, or substantially reduce, PMN depressions in mice. The neutralizing activity was shown to be associated with the immunoglobulin fractions of sera and therefore appears to be due to an antibody. Cerebrospinal fluids from MS, but not other, patients also strongly neutralized MSAA. Evidence has been presented that sera from MS patients may contain both MSAA and MSAA neutralizing antibodies. Antigen-antibody complexes were separated from such sera by high-speed centrifugation, and neutralizing antibodies were dissociated from them at a low pH. Whereas the data are as yet limited due to the vagaries and complexities of the test procedures, they provide further evidence that MSAA is not an indigenous virus of experimental animals, causes infections in man, and is indeed closely associated with MS. If it were the cause of MS, which remains to be ascertained, the data imply that not all infections by MSAA lead to the development of MS.