Activity profile in multiple sclerosis: an integrative approach. A preliminary report

In order to define an activity profile in patients with multiple sclerosis (MS), T-cell subpopulations and proliferative responses to myelin basic protein (MBP) associated with anti-MBP antibodies, nitrotyrosine levels in serum and cerebrospinal fluid (CSF), and serum CD40L (sCD154) were simultaneously assessed in 29 consecutive and untreated MS patients. When compared to controls, patients in secondary progressive stable (SP/I), or in full remission (RR/I) stages, individuals with secondary progressive active disease (SPIA) or in acute relapse (RR/A) showed a significant decrease of CD4/CD45RA+ T cells associated with an increase of absolute numbers of CD4/45R0+ T cells (p < 0.001). In addition, in vitro-specific T-cell proliferative responses against MBP (SP/A, RR/A, SP/I: p < 0.001 versus controls) in association with augmented sCD154 serum levels (SP/A, RR/A, versus controls p < 0.001) and a significant increase of both CSF and serum levels of anti-MBP antibodies and nitrotyrosine levels (p < 0.001) were also found. Thus, the simultaneous evaluation of antibody and cell-mediated immunopathological parameters, along with the effector mediators of inflammation such as the nitric oxide products, offers a new integrative approach to characterize markers of clinical activity in MS patients, which may be used at the moment of the initial diagnosis and during an apparent recurrences of the disease to monitor therapeutic protocols and to determine whether immune-based nerve destruction mechanisms are still operating in patients with few clinical findings.