A prospective, observational study on conversion of clinically isolated syndrome to multiple sclerosis during 4-year period (MS NEO study) in Taiwan.

IMPORTANCE: CIS to MS conversion rates vary depending on population cohorts, initial manifestations, and durations of follow-up. OBJECTIVE: To investigate conversion rate of patients from CIS to MS and the prognostic significance of demographic and clinical variables in Taiwanese population. DESIGN: Nationwide, prospective, multi-centric, observational study from November 2008 to November 2014 with 4 years follow-up. SETTING: Multi-centre setting at 5 institutions in Taiwan. PARTICIPANTS: 152 patients having single clinical event potentially suggestive of MS in last 2 years were enrolled as consecutive sample. 33 patients were lost to follow-up and 16 patients did not complete the study.103 patients completed the study. INTERVENTION(S) (FOR CLINICAL TRIALS) OR EXPOSURE(S) (FOR OBSERVATIONAL STUDIES): Natural progression from first episode of CIS to MS or NMO was observed. MAIN OUTCOME(S) AND MEASURE(S): Variables analysed were 'proportion of patients converting to MS or NMO after first episode of CIS', 'duration between first episode of neurological event and diagnosis of MS', 'status of anti-AQP4 IgG' and 'length of longest contiguous spinal cord lesion in MS patients'. Association between baseline characteristics and progression to MS from CIS was analyzed using multiple logistic regression. Multivariate time dependent effect of baseline characteristics on progression to MS was plotted. RESULTS: 14.5% patients with CIS converted to MS after 1.1 ± 1.0 years with greater predisposition (18.8%) in those having syndromes referable to the cerebral hemispheres. Conversion rate from ON to MS was 9.7%. 90.9% patients had mild disease course. 46.7% patients had abnormal MRIs at baseline, with 0.6±0.5 contrast enhanced lesions. 'Below normal BMI' and 'MRI lesion load (≥ 4 lesions)' were identified as risk indicators for the development of MS. Amongst the patients who developed NMO as diagnosed by modern criteria, 80% were positive for anti-AQP4 IgG antibody. CONCLUSIONS AND RELEVANCE: 'Below normal BMI' and 'number of demyelinating lesions (≥4)' are significant predictors of conversion from CIS to MS. A low conversion rate to MS in Taiwanese CIS patients and majority of them having a mild course and minimal disability suggest the roles of geographic, genetic and ethnic factors. TRIAL REGISTRATION: Non-trial observational study.

Combinatorial HLA-peptide bead libraries for high throughput identification of CD8⁺ T cell specificity.

Comprehensive antigenic characterization of a T cell population of unknown specificity is challenging. Existing MHC class I expression systems are limited by the practical difficulty of probing cell populations with an MHC class I peptide library and the cross-reactivity of T cells that are able to recognise many variants of an index peptide. Using emulsion PCR and emulsion in vitro transcription/translation of a random library of peptides conjugated to CD8-null HLA-A*0201 on beads, we probed HLA-A*0201-restricted T cells with specificity for influenza, CMV and EBV. We observed significant enrichment for sequences containing HLA-A2 anchors and correct viral fragments for all T cell populations. HLA bead display provides a novel approach to identify the specificity of T cells.

A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.

Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.

Linking genotype to phenotype on beads: high throughput selection of peptides with biological function.

Although peptides are well recognised biological molecules in vivo, their selection from libraries is challenging because of relative low affinity whilst in linear conformation. We hypothesized that multiplexed peptides and DNA on the surface of beads would provide a platform for enhanced avidity and the selection of relevant peptides from a library (ORBIT bead display). Using human immunodeficiency virus (HIV-1) gp120 as a target, we identify peptides that inhibit HIV-1 replication in vitro through blocking of protein:protein interaction with the co-receptor CCR5. The bead display approach has many potential applications for probing biological systems and for drug lead development.

Cellular and cytokine correlates of severe dengue infection.

BACKGROUND: The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF. METHODOLOGY/PRINCIPAL FINDINGS: By using ex vivo IFNγ ELISpot assays we determined DENV-NS3 specific responses in patients with varying severity of DHF. Other cytokines produced by DENV-NS3 specific T cells were determined by using multiple bead array analysis (MBAA). We also determined the serum cytokine levels using MBAA, lymphocyte subsets and Annexin V expression of lymphocytes in patients with varying severity of DHF. Of the 112 DHF patients studied, 29 developed shock. Serum IL-10 and IP-10 levels positively and significantly correlated with T cell apoptosis while IL-10 levels inversely correlated with T cell numbers. In contrast, TGFß showed a very significant (P<0.0001) and positive correlation (Spearman's R = 0.65) with the platelet counts, consistent with platelet release. We found that whilst patients with severe dengue had lower total T cell numbers, the DV-NS3 specific T cells persisted and produced high levels of IFNγ but not TNFα, IL-3, IL-13, IL-2, IL-10 or IL-17. CONCLUSIONS/SIGNIFICANCE: Our data suggest that serum IL-10, TNFα and TGFß differentially associate with dengue disease severity.

A web-based decision support system for dietary analysis and recommendations.

OBJECTIVES: Because of lack of integrated databases for Chinese menus and the need for nutrition information by dietitians in Taiwan, we developed a Web-based platform for dietary analysis and recommendations. METHODS: The fuzzy decision model was utilized to develop a Web-based support system that searches food composition databases, calculates dietary intake, and provides the guidance for decision making in nutrition counseling. RESULTS: The online support system generated menu- or food-based recommendations using a fuzzy decision model. The homogeneity of food composition between five selected menus generated by the fuzzy decision model in a randomly selective case was strongly correlated with a correlation coefficient of 0.31-0.99. The correlation coefficients were 0.42-0.45 and 0.13-0.44 between food composition of five most correlated menus or five selected menus generated by the fuzzy decision model and nutrient requirements computed by the fuzzy decision model, respectively. The most correlated menus and the menus generated by the fuzzy decision model were also similar. CONCLUSIONS: The recommended menus generated by the fuzzy decision model are considerably reliable and valid, and the online support system for dietary analysis and recommendations can provide a Web-based and decision-making tool for dietitians in Taiwan.