Diabetes-associated autoantibodies among young diabetes mellitus patients in Malaysia

Introduction: Diabetes-associated autoantibodies (DAA) is the hallmark of T1DM and LADA which are frequently tested in young diabetes patients. It was noted that up to 10-15% of patients with initial diagnosis of T2DM also exhibit DAA. Regardless of the classification, the presence of DAA suggests an underlying islet autoimmunity which lead to progressive pancreatic β-cell failure. There is limited data reported on DAA in young diabetes patients in Malaysia. This study aims to determine the frequency of DAA positivity and its association with demographic and clinical characteristics among this cohort. Methods: A retrospective study using secondary data obtained from Allergy and Immunology Research Centre, Institute for Medical Research, Malaysia. This study included 194 diabetes patients who were diagnosed before the age of 40 years old and tested for GADA, ICA, IA2A and IAA. Results: From 194 patients, 91 (46.9%) were positive for least one of the following DAA: ICA (79, 40.7%), GADA (61, 31.4%), IA2A (37, 19.1%) and IAA (9, 4.6%). Multiple positivity was higher (73.6%) compared to single positivity. Highest combination of double positivity was ICA+GADA (54, 59.3%) and triple positivity was ICA+GADA+IA2A (25, 27.5%). Simultaneous positivity of four autoantibodies was seen in only one (1.1%) patient. ICA, GADA and IA2A were associated with age group and ethnicity (all p < 0.001). Only IA2A was associated with gender (p = 0.012). Conclusions: GADA, ICA ad IA2A are more significant in young Malaysian diabetes patients. IAA has a very low frequency in this studied population

Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available in Diabetes in print and online at http://diabetes.diabetesjournals.orgThe erratum to this article is available in ORE at http://hdl.handle.net/10871/40335Studies in type 1 diabetes indicate potential disease heterogeneity, notably in the rate of β-cell loss, responsiveness to immunotherapies, and, in limited studies, islet pathology. We sought evidence for different immunological phenotypes using two approaches. First, we defined blood autoimmune response phenotypes by combinatorial, multiparameter analysis of autoantibodies and autoreactive T-cell responses in 33 children/adolescents with newly diagnosed diabetes. Multidimensional cluster analysis showed two equal-sized patient agglomerations characterized by proinflammatory (interferon-γ-positive, multiautoantibody-positive) and partially regulated (interleukin-10-positive, pauci-autoantibody-positive) responses. Multiautoantibody-positive nondiabetic siblings at high risk of disease progression showed similar clustering. Additionally, pancreas samples obtained post mortem from a separate cohort of 21 children/adolescents with recently diagnosed type 1 diabetes were examined immunohistologically. This revealed two distinct types of insulitic lesions distinguishable by the degree of cellular infiltrate and presence of B cells that we termed "hyper-immune CD20Hi" and "pauci-immune CD20Lo." Of note, subjects had only one infiltration phenotype and were partitioned by this into two equal-sized groups that differed significantly by age at diagnosis, with hyper-immune CD20Hi subjects being 5 years younger. These data indicate potentially related islet and blood autoimmune response phenotypes that coincide with and precede disease. We conclude that different immunopathological processes (endotypes) may underlie type 1 diabetes, carrying important implications for treatment and prevention strategies.JDRFNational Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College LondonEuropean Union (EU FP7) award - Persistent Virus Infection in Diabetes Network Study Group (PEVNET)EU FP7 Large-Scale Focused Collaborative Research Project on Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes (NAIMIT)EU FP7 Large-Scale Focused Collaborative Research Project on β-cell preservation through antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems (EE-ASI)National Institutes of Health (NIH)National Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Research ResourcesGeneral Clinical Research CenterAmerican Diabetes Association (ADA

Antibacterial and antifungal activities of Cymbopogon nardus essential oil

Essential oils and their components are becoming increasingly popular as naturally occurring antimicrobial agents. In this study the chemical composition and antimicrobial activity of Cymbopogon nardus essential oils were determined. The essential oil components which were identified by GCMS analysis are as follows: β-terpinyl acetate, isopulegol, cis-geraniol, citronellyl formate, L-β-pinene, δ-cadinene, γ-elemene and seychellene. The minimum inhibitory concentration (MIC) of essential oils against a few selected pathogenic bacteria (Staphylococcus aureus ATCC 25923, Bacillus anthracis ATCC 14578, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 35218) and fungi (Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 90112) were determined using disc diffusion method. The essential oils showed slightly potent inhibitory effects with mean diameter of inhibition zones ranging from 7.5 mm to 9.0 mm. Similar results were also obtained for the fungi, where the essential oils showed inhibitory effects with slightly wider diameter of inhibition zones which ranged from 7.8 mm to 12.0 mm. All microorganisms showed sensitivity towards C. nardus except for P. aeruginosa. The MIC values against these microorganisms ranged from 4.69 mg/mL to 37.5 mg/mL. The findings thus indicate the possibility of exploiting C. nardus essential oil as an effective inhibitor for the growth of some pathogenic microorganisms in the field of medicine

Seroprevalence of diphtheria toxoid IgG antibodies in the Malaysian population

Abstract Background Despite high childhood immunization coverage, sporadic cases of diphtheria have been reported in Malaysia in recent years. This study aims to evaluate the seroprevalence of diphtheria among the Malaysian population. Methods A total of 3317 respondents age 2 years old to 60 years old were recruited in this study from August to November 2017. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of IgG antibody against the toxoid of C. diphtheriae in the blood samples of respondents. We classified respondent antibody levels based on WHO definition, as protective (≥0.1 IU/mL) and susceptible (< 0.1 IU/mL) to C. diphtheriae infection. Results Among the 3317 respondents, 57% were susceptible (38.1% of children and 65.4% of adults) and 43% (61.9% of children and 34.6% of adults) had protective antibody levels against diphtheria. The mean antibody level peaked among individuals aged 1–2 years old (0.59 IU/mL) and 6–7 years old (0.64 IU/mL) but generally decreased with age, falling below 0.1 IU/mL at around 4–6 years old and after age 20 years old. There was a significant association between age [Children: χ2 = 43.22(df = 2),p < 0.001)], gender [Adults: χ2 = 5.58(df = 1),p = 0.018] and ethnicity [Adults: χ2 = 21.49(df = 5),p = 0.001] with diphtheria toxoid IgG antibody level. Conclusions About 57% of the Malaysian population have inadequate immunity against diphtheria infection. This is apparently due to waning immunity following childhood vaccination without repeated booster vaccination in adults. Children at age 5–6 years old are particularly vulnerable to diphtheria infection. The booster vaccination dose normally given at 7 years should be given earlier, and an additional booster dose is recommended for high-risk adults