Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy.

OBJECTIVE: Here we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets. RESEARCH DESIGN AND METHODS: We compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs. RESULTS: Patients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vß/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures. CONCLUSIONS: T1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs. TRIAL REGISTRATION NUMBER: EudraCT 2014-004319-35.

Spinal cord lesions in children and adolescents with multiple sclerosis - Magnetic resonance imaging.

PURPOSE: The purpose of our study was to determine the prevalence of spinal cord lesions revealed by magnetic resonance (MR) imaging in children and adolescents with clinically definite multiple sclerosis (MS). MATERIAL AND METHODS: We retrospectively evaluated the spinal cord magnetic resonance examinations in a group of MS patients consisting of 58 children (37 girls and 21 boys) aged from 7 to 17.8 years (mean 13.7 years). All children met the criteria of clinically definite MS and had typical MS lesions revealed in the brain imaging. RESULTS: Spinal cord lesions, regardless of localization, were identified in 36 (62%) patients. In 22 of 58 patients (38%) no lesions were observed. The plaques were found in the cervical spinal cord and the thoracic spinal cord in 30 out of 36 (86.1%) and in 31 out of 36 (88.6%) patients, respectively. Contrast enhancement was noticed in 10 out of 36 patients (27.7%) and was not correlated with the number of lesions present. We noticed a tendency to higher EDSS score in patients with lesions in more than 1 spinal cord region. Our study showed that spinal cord lesions are more frequently present in patients with complex neurological disability. CONCLUSION: The prevalence of spinal cord lesions in children and adolescents with MS is high. Therefore, spinal cord MRI should be included in diagnostic program of MS.

Strains differentiation of Microsporum canis by RAPD analysis using (GACA)4 and (ACA)5 primers.

Molecular analysis of dermatophytes (based on PCR fingerprinting) revealed high clonal differentiation between the genus and species. Microsporum canis (zoophilic dermatophyte, belonging to genus Microsporum), responsible for most cases of tinea capitis in children, tinea corporis in adults and dermatophytoses in cats, is very unique in comparison with other dermatophytes. Results of most molecular studies show that there is no clonal differentiation within M. canis as distinct from other species. The aim of this study was application of (GACA)4 repetitive primer and (ACA)5 primer for typing of M. canis strains isolated from human and animals in Central Poland. Fungal strains: 32 clinical isolates of M. canis, originated from patients from Central Poland; 11 strains isolated from infected cats (6) and dogs (7), reference strains of M. canis (CBS 113480), T rubrum (CBS 120358), T mentagrophytes (CBS 120357) and E. floccosum (CBS 970.95). The genomic DNAs of the strains were used as a template in RAPD reaction. No differentiation was observed for the analyzed M. canis strains using (GACA)4 and (ACA)5 typing.