The vitamin D receptor TaqI TT genotype is associated with type 1 diabetes in the Black South African population.

Polymorphisms in the vitamin D receptor (VDR) gene (BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236)) and low vitamin D concentrations have previously been associated with type 1 diabetes (T1D). Vitamin D is thought to mediate the switch from a pro-inflammatory Th1 response to an anti-inflammatory Th2 response which is protective against the development of T1D. These associations are inconsistent across studies and population groups.

The association of vitamin D binding protein levels and genotypes with type 1 diabetes in the black South African population.

Background: Vitamin D deficiency and the vitamin D pathway have previously been associated with type 1 diabetes (T1D). The majority of vitamin D is transported through the blood bound to the vitamin D binding protein (VDBP). Two polymorphisms in the VDBP gene (rs4588 and rs7041) result in different VDBP variants and have been associated with T1D, however the results are not consistent.

Zinc transporter 8 (ZnT8) autoantibody prevalence in black South African participants with type 1 diabetes.

Background: Autoantibodies to β-cell specific antigens are markers of type 1 diabetes. The most recently identified autoantibodies are targeted to the zinc transporter 8 (ZnT8) protein located in the membrane of β-cell insulin secretory granules. The prevalence of ZnT8 autoantibodies in newly diagnosed participants with type 1 diabetes has been found to range from 33 to 80 %.

A Polymorphism in the Gene Encoding the Insulin Receptor Binding Protein ENPP-1 Is Associated with Decreased Glomerular Filtration Rate in an Under-Investigated Indigenous African Population.

Introduction: The C allele of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP-1) rs1044498 polymorphism has previously been associated with increased binding of ENPP-1 to the insulin receptor (IR), resulting in decreased IR signalling and enhanced insulin resistance. It has also been associated with reduced kidney function in participants with diabetes of predominantly European and Asian descent. The association of this polymorphism with kidney disease in healthy Black South African participants has yet to be ascertained.

Evaluation of the impact of delayed centrifugation on the diagnostic performance of serum creatinine as a baseline measure of renal function before antiretroviral treatment.

Background: The measurement of serum creatinine is a standard requirement of the medical management of people living with HIV. Renal dysfunction is common, both as a complication of HIV-infection and as a result of its treatment. The detection of abnormal renal function before the start of antiretroviral therapy will impact patient management and the outcome of treatment.

Identification of a subgroup of black South Africans with type 1 diabetes who are older at diagnosis but have lower levels of glutamic acid decarboxylase and islet antigen 2 autoantibodies.

Aims: To compare the age at diagnosis and prevalence of islet autoantibody [glutamic acid decarboxylase (65 kDa) 65 and islet antigen 2] positivity in black and white participants with type 1 diabetes in South Africa, and to analyse the relationship between age at diagnosis and the presence of autoantibodies.

Methods: Participants were recruited from diabetes outpatient departments and autoantibodies to glutamic acid decarboxylase (65 kDa) and islet antigen 2 were measured by enzyme-linked immunosorbent assay.

Results: We recruited 472 (353 black and 119 white) participants with type 1 diabetes.

Effect of two monoterpene phenols on antioxidant defense system in Candida albicans.

Thymol and carvacrol from the class of monoterpene phenols are one of the most potent plant essential oil components possessing antimicrobial effects. Known for their wide bioactive spectrum, these positional isomers of isopropyl cresol deplete ergosterol content, compromise membrane permeability, block efflux pumps and restore antifungal susceptibility to fluconazole in resistant Candida strains. Exposure to these natural compounds induces a cascade of stress responses, which are important to comprehend their microbicidal mechanisms.

Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function.

Graves' disease is characterized by production of agonist antibodies to the thyroid-stimulating hormone receptor (TSHR), but knowledge of the genetic and somatic events leading to their aberrant production is limited. We describe the genetic analysis of two monoclonal antibodies (mAbs) with thyroid-stimulating activity (TSAb) obtained from a single mouse with experimental Graves' disease. The mAbs were class switched, but used the same rearrangement of immunoglobulin heavy chain, variable region (IGHV) and immunoglobulin light chain, variable region (IGLV) germline genes, implying a clonal relationship and derivation from a single precursor B-cell clone.

Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies.

Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66+/-22%, upon treatment with rituximab and methimazole for 21 days (p<0.

Longitudinal epitope analysis of insulin-binding antibodies in type 1 diabetes.

Autoantibodies to insulin (IAA) are one of the first markers of the autoimmune process leading to type 1 diabetes (T1D). While other autoantibodies in T1D have been studied extensively, relatively little is known about IAA and their binding specificities, especially after insulin treatment is initiated. We hypothesize that insulin antibodies (IA) that develop upon initiation of insulin treatment differ in their epitope specificities from IAA.

Analysis of GAD65 autoantibodies in Stiff-Person syndrome patients.

Autoantibodies to the 65-kDa isoform of glutamate decarboxylase GAD65 (GAD65Ab) are strong candidates for a pathological role in Stiff-Person syndrome (SPS). We have analyzed the binding specificity of the GAD65Ab in serum and cerebrospinal fluid (CSF) of 12 patients with SPS by competitive displacement studies with GAD65-specific rFab-derived from a number of human and mouse mAbs specific for different determinants on the Ag. We demonstrate considerable differences in the epitope specificity when comparing paired serum and CSF samples, suggesting local stimulation of B cells in the CSF compartment of these patients.

Epitope analysis of insulin autoantibodies using recombinant Fab.

Autoantibodies to insulin are often the first autoantibodies detected in young children with type 1 diabetes and can be present before the onset of clinical diabetes. These autoantibodies and their epitopes are, however, not well characterized. We explored the use of monoclonal antibodies and their recombinant Fab as reagents for epitope analysis.

Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetes-specific GAD65Abs.

Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1 diabetes development, but the conformational nature of the GAD65Ab epitopes complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and 221-442.

Cystic fibrosis carrier frequencies in populations of African origin.

Cystic fibrosis (CF) is a common autosomal recessive disorder in populations of European descent. However, very little is known about CF in populations of African origin among whom it has been believed to be extremely rare. The aim of this study was to determine if this is the case or whether it is under-reported.