Prolonged dynamic clinico-immunological observation of 85 patients with definite multiple sclerosis: first steps towards monitoring process activity.

Abstract

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of beta-endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immunoregulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation--including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages--often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.