Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients

Abstract

To investigate whether peripheral immune abnormalities are associated with brain inflammation in multiple sclerosis, and whether differences in MRI activity are paralleled by changes in leukocyte composition, we conducted a prospective longitudinal study in patients at their clinical onset. Twenty patients presenting a first inflammatory event in the central nervous system suggestive of multiple sclerosis underwent, every 45 days for one year, immunophenotyping of 98 blood cell subsets together with brain MRI and clinical evaluation. Six patients showed intense MRI activity, six patients did not display MRI activity, while the remaining 8 patients had low (i.e. intermediate) MRI activity during the follow-up. Our results show that MRI-active and MRI-inactive patients display significant differences in ten lymphocyte subsets. Among these, there are both effector (CCR7-CD45RA-CD4+ alphabeta T cells, CCR5+ gammadelta T cells) and regulatory (DN CD28+ alphabeta T cells and CD25+CD8+ alphabeta T cells) lymphocytes pertaining to the innate and the acquired arms of the immune system. Moreover, these differences were, upon employment of a class prediction procedure based on "support vector machines" algorithm utilizing leave-one-out cross validation procedures, able to correctly assign patients to their respective MRI activity group. All 6 MRI-active and 6 MRI-inactive patients were correctly classified, and, upon application of a class prediction model in an unsupervised manner to the 8 patients with intermediate MRI activity, 6 were predicted as MRI-active and 2 as MRI-inactive patients. Also, when the mean values of the first three time points (T0, T1 and T2) were used for the prediction of all patients, the selected lymphocyte subsets correctly classified 90% of patients. Sensitivity was 91.7% and specificity was 87.5%. These results provide evidence showing that brain inflammation in multiple sclerosis is associated with distinct changes in peripheral lymphocyte subsets, and raise the possibility that the identified subsets may, after adequate validation, assist in the prediction of MRI activity in the early stages of multiple sclerosis.

No evidence of JC virus reactivation in natalizumab treated multiple sclerosis patients: an 18 month follow-up study

“…Such changes were natalizumab related, as shown by comparison with a cohort of untreated MS patients 21. Except for the B cell percentage, mean values for all of the other circulating immune cells analysed remained within the normal range (table 5).…”

“…For the prospective flow cytometry analysis of blood immune cell subsets, whole blood direct staining was performed using a standard procedure 21. Stained cells were analysed on a two laser flow cytometer (FACSCalibur; BD Immunocytometry Systems, San Jose, California, USA), using Cell Quest and DIVA software (BD Biosciences, San Jose, California, USA) for data acquisition and analysis, respectively.…”

Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases

“…Consequently, there is an unmet medical need for novel immunomodulators with different mechanisms of action and͞or adverse-effect profiles from existing drugs. Although the frequency of autoreactive T cells in healthy individuals and in patients with autoimmune diseases is similar (8,9), disease-associated autoreactive T cells are mainly costimulation-independent CCR7 Ϫ T EM cells, whereas autoreactive T cells in healthy individuals are naïve͞T CM cells (10)(11)(12)(13)(14)(15)(16). Therapies that selectively suppress T EM cells without affecting other lymphoid subsets would have immense value.…”

Gamma delta T cells in non‐immune patients during primary schistosomal infection

“…The syndrome is unique to the non-immune population (usually travelers), appears 3–8 weeks after exposure to the Schistosoma cercaria, and may be related to immune complexes containing schistosomal antigens. In healthy individuals, the percent of γδ T cells within the total CD3+ T cell population is generally stable over time, and only change in specific stimulatory circumstances, for example, when patients are treated with intravenous administration of bisphosphonate for osteoporosis, which increases monocyte expression of IPP, a γδ T cell antigen, or in multiple sclerosis patients with active brain disease, by unknown mechanisms [20,21]. Our results now reveal for the first time, a relative expansion of γδ T cells within the total CD3+ T cell population in the PB in a group of patients from non-endemic areas who were infected with Schistosoma , following treatment of the infection.…”