GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection.

Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.

Immune monitoring of Trichuris suis egg therapy in multiple sclerosis patients.

Initial clinical trials using Trichuris suis eggs (TSO) in autoimmune diseases such as inflammatory bowel disease, revealed a striking suppressive effect on the autoimmune response. Here, we analysed the effect of TSO therapy on the course of multiple sclerosis (MS), as a Th1/Th17-associated autoimmune disease. Different immunological parameters in four patients with secondary progressive MS were surveyed during a 6-month therapy with TSO, focusing on the modulation of T-cell Th1-Th2 balance as well as on the innate immune response. We are able to show a slight downregulation of the Th1-associated cytokine pattern, especially relevant in interleukin (IL)-2 (P < 0.05 after 2 months of therapy), with a temporary increase of Th2-associated cytokines such as IL-4. Furthermore, mild eosinophily and changes in CD4+ and CD8+T cells and natural killer (NK) CD56 bright cell numbers were observed. The findings observed in this group of patients suggest that TSO therapy has a moderate immunomodulatory impact in MS.

Three screening batteries to detect cognitive impairment in multiple sclerosis.

To compare the sensitivities for detecting cognitive impairment in patients with multiple sclerosis (MS) and administration times of three brief batteries of neuropsychological tests, 64 patients with MS completed the Neuropsychological Screening Battery for Multiple Sclerosis (NPSBMS), the Screening Examination for Cognitive Impairment (SEFCI), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Failure on a particular test was defined as a score below the 5th percentile for healthy controls, and the number of patients who failed at least one or two tests (out of four) was determined for each battery. Both the SEFCI and the NPSBMS identified significantly more patients with impairment than the RBANS, which was no more sensitive than the Mini-Mental State Exam (MMSE). Results were similar at both the one- and two-failed-tests criteria, but there were no significant differences between the SEFCI and the NPSBMS at either failure criterion. Mean administration time was 22.6 min for the SEFCI compared to 31.7 min for the NPSBMS (p < 0.001). Eleven (17%) of the patients refused to attempt the Paced Auditory Serial Addition Test (PASAT), one component of the NPSBMS. For screening patents on a single occasion, the SEFCI is preferred because its administration time is shorter than the NPSBMS.