Statistical assessment of reliability of anthropometric measurements in the multi-site South African National Dietary Intake Survey 2022.

Background: Anthropometric data quality in large multicentre nutrition surveys is seldom adequately assessed. In preparation for the South African National Dietary Intake Survey (NDIS-2022), this study assessed site leads' and fieldworkers' intra- and inter-rater reliability for measuring weight, length/height, mid-upper arm circumference (MUAC), waist circumference (WC) and calf circumference (CC).

Methods: Standardised training materials and measurement protocols were developed, and new anthropometric equipment was procured.

Outcome measures in Angelman syndrome.

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children's functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials.

Household food insecurity in South Africa from 1999 to 2021: a metrics perspective.

Objective: To review and synthesize studies on household food security in South Africa.

Design: Systematic mapping review of metrics (methodological review).

Setting: Electronic databases, including EBSCOHost, Scopus and Web of Science, were searched for studies and reports on household food security in South Africa, reporting household food security published between 1999 and 2021.

Peripheral blood cellular dynamics of rheumatoid arthritis treatment informs about efficacy of response to disease modifying drugs.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation and is mediated by multiple immune cell types. In this work, we aimed to determine the relevance of changes in cell proportions in peripheral blood mononuclear cells (PBMCs) during the development of disease and following treatment. Samples from healthy blood donors, newly diagnosed RA patients, and established RA patients that had an inadequate response to MTX and were about to start tumor necrosis factor inhibitors (TNFi) treatment were collected before and after 3 months of treatment.

Molecular signature of methotrexate response among rheumatoid arthritis patients.

Background: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but failure of satisfying treatment response occurs in a significant proportion of patients. Here we present a longitudinal multi-omics study aimed at detecting molecular and cellular processes in peripheral blood associated with a successful methotrexate treatment of rheumatoid arthritis.

Methods: Eighty newly diagnosed patients with RA underwent clinical assessment and donated blood before initiation of MTX, and 3 months into treatment.

Musculoskeletal Conditions in Persons Living with HIV/AIDS: A Scoping Review.

Objective: Globally 37.9 million people are living with HIV/AIDS, and with mortality rates declining, there is an increasing focus on comorbidities including musculoskeletal (MSK) disorders. Therefore, the aim of this scoping review was to generate and summarize an overview of the existing scientific literature dealing with MSK complaints in people living with HIV/AIDS (PLWHAs).

Predictive value of different body segments to estimate height in a South African adult hospital population.

Background And Aims: Height measurement is a vital component for assessing nutritional risk, and calculating dietary requirements in a clinical setting where indirect calorimetry is not available. In many patients, height cannot be measured accurately, and equations based on body segments are relied on to predict height. This study aimed to evaluate if specific body segments are better associated with height than others in a South African public hospital setting.

Early prediction of clinical response to anti-TNF treatment using multi-omics and machine learning in rheumatoid arthritis.

Objectives: Advances in immunotherapy by blocking TNF have remarkably improved treatment outcomes for Rheumatoid arthritis (RA) patients. Although treatment specifically targets TNF, the downstream mechanisms of immune suppression are not completely understood. The aim of this study was to detect biomarkers and expression signatures of treatment response to TNF inhibition.

Identifying novel B-cell targets for chronic inflammatory autoimmune disease by screening of chemical probes in a patient-derived cell assay.

B-cell secretion of autoantibodies drives autoimmune diseases, including systemic lupus erythematosus and idiopathic inflammatory myositis. Few therapies are presently available for treatment of these patients, often resulting in unsatisfactory effects and helping only some of the patients. We developed a screening assay for evaluation of novel targets suspending B-cell maturation into antibody secreting cells, which could contribute to future drug development.

Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E Production.

We screened 57 chemical probes, high-quality tool compounds, and relevant clinically used drugs to investigate their effect on pro-inflammatory prostaglandin E (PGE) production and interleukin-8 (IL-8) secretion in human whole blood. Freshly drawn blood from healthy volunteers and patients with systemic lupus erythematosus (SLE) or dermatomyositis was incubated with compounds at 0.1 or 1 µM and treated with lipopolysaccharide (LPS, 10 µg/ml) to induce a pro-inflammatory condition.

A genetics-led approach defines the drug target landscape of 30 immune-related traits.

Most candidate drugs currently fail later-stage clinical trials, largely due to poor prediction of efficacy on early target selection. Drug targets with genetic support are more likely to be therapeutically valid, but the translational use of genome-scale data such as from genome-wide association studies for drug target discovery in complex diseases remains challenging. Here, we show that integration of functional genomic and immune-related annotations, together with knowledge of network connectivity, maximizes the informativeness of genetics for target validation, defining the target prioritization landscape for 30 immune traits at the gene and pathway level.

Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.

Background: Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA).

Method: RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis.

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson's disease.

Individuals with Parkinson's disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression.

Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.

Objectives: During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis.

Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis: results from the COMBINE study.

Objective: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.

Synergistic effects of ethanol and isopentenyl pyrophosphate on expansion of γδ T cells in synovial fluid from patients with arthritis.

Low to moderate ethanol consumption has been associated with protective effects in autoimmune diseases such as rheumatoid arthritis, RA. An expansion of γδ T cells induced by isopentenyl pyrophosphate, IPP, likewise seems to have a protective role in arthritis. The aim of this project was to test the hypothesis that low doses of ethanol can enhance IPP-induced expansion of synovial fluid γδ T cells from patients with arthritis and may thereby potentially account for the beneficial effects of ethanol on symptoms of the arthritic process.

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid.

Accumulation and activation of natural killer cells in local intraperitoneal HIV-1/MuLV infection results in early control of virus infected cells.

Natural killer (NK) cells are important effectors in resistance to viral infections. The role of NK cells in the acute response to human immunodeficiency virus 1 (HIV-1) infected cells was investigated in a mouse model based on a HIV-1/murine leukemia virus (MuLV) pseudovirus. Splenocytes infected with HIV-1/MuLV were injected intraperitoneally and local immunologic responses and persistence of infected cells were investigated.

NK cell function and antibodies mediating ADCC in HIV-1-infected viremic and controller patients.

Natural killer (NK) cells have been suggested to play a protective role in HIV disease progression. One potent effector mechanism of NK cells is antibody-dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding to the FcγRIIIa receptor (CD16) on NK cells. We investigated NK cell-mediated ADCC function and the presence of ADCC antibodies in plasma from 20 HIV-1-infected patients and 10 healthy donors.

The interplay between Leishmania promastigotes and human Natural Killer cells in vitro leads to direct lysis of Leishmania by NK cells and modulation of NK cell activity by Leishmania promastigotes.

NK cells represent one of the first lines of defence in the immune reaction after invasion of Leishmania parasites. Depletion of mouse natural killer (NK) cells dramatically enhances susceptibility of normally resistant mice. In this study we evaluated the fate of NK cells and parasites after contact formation.

Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.

The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission.

Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways.

Background Aims: Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties.

Methods: We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells.