A homogeneous bioluminescent inhibition immunoassay to detect anti-interferon gamma antibodies.

Adult-onset immunodeficiency with antibodies to interferon-γ (AOID with AIGA), is a rare, acquired immunodeficiency causing susceptibility to disseminated non-tuberculous mycobacteria and other intracellular opportunistic infections. The diagnosis depends on demonstrating the presence of endogenous anti-interferon-γ antibodies (AIGA) that suppress Th1 cell mediated immunity. Bioluminescent immunoassays are a newly emerging immunoassay format which utilise the action of bioluminescent enzymes on a substrate for specific analyte detection. In-short, detecting antibodies are conjugated with a bioluminescent enzyme. The detecting antibodies bind the analyte of interest and produce light (luminescence) after addition of a substrate. The purpose of this study was to evaluate two newly developed bioluminescent immunoassays using Lumit® (Promega) technology as a diagnostic test for AOID with AIGA. Specific aims included the clinical validation of a new inhibition bioluminescent immunoassay technique to detect AIGA which block detection of interferon-γ (IFN-γ) in-vitro and correlation of inhibition bioluminescent immunoassay results with AOID with AIGA disease status. Two bioluminescent inhibition immunoassays were developed. One which adapted an existing kit from Promega (Lumit® Human IFN-γ Immunoassay) and one which was developed in-house. 87 healthy controls and 48 patients with previously diagnosed AOID with AIGA were recruited and tested using these two methods. Results showed both bioluminescent inhibition immunoassays were able to clearly discriminate between AOID with AIGA patients and healthy controls. The mean inhibition percentage between patient groups correlated with disease activity. Both assays appeared to be more sensitive when compared to the existing inhibition ELISA.

Intravenous immunoglobulin infusion contributes to a high incidence of false reactive screen results for human T-lymphotropic virus.

Intravenous immunoglobulin (IVIg) has been increasingly used to treat immunodeficiencies and inflammatory disorders. However, IVIg has also been shown to affect a wide range of laboratory testing, including human T-lymphotropic virus (HTLV) screening. Our laboratory frequently observes false reactive HTLV screens from patients receiving IVIg infusions, however the extent of IVIg contribution to the false reactivity has not been extensively investigated. The objective of this study was to explore the prevalence of HTLV-1/2 infection in patients from the Sydney metropolitan area and evaluate the positive predictive value for HTLV screening test in sera from patients with or without IVIg infusions. HTLV screening test results from sera of 3843 patients referred to Central Sydney Immunology Laboratory between June 2006 and May 2021 were retrospectively analysed. Among 72 (1.9%) sera reactive on screening enzyme-linked immunosorbent assay (ELISA), 62 (86.1%) were from patients receiving IVIg infusions, including 60 collected post-IVIg and two collected pre-IVIg infusions. Only two (3.3%) of the 60 post-IVIg sera were positive on confirmatory western blot. In contrast, in non-IVIg sera, five (50.0%) from the 10 screen-reactive sera were positive on western blot. If positive western blot is used as the reference for determining 'true' HTLV infection, we found the positive predictive value of HTLV screening ELISA in sera collected post-IVIg (3.3%) is considerably lower than that in non-IVIg and pre-IVIg sera (41.7%). The vast majority of false reactive screen results (89.2%) in our study cohort were from sera collected post-IVIg infusion. Our study suggests that the high incidence of falsely reactive results in HTLV screening ELISA could be attributed to IVIg infusion. Hence, collection of sera from patients on IVIg should be avoided and screen-reactive results should be interpreted with greater caution, particularly for patients from non-endemic areas.

Body weight management in overweight and obese breast cancer survivors.

BACKGROUND: Studies suggest that overweight and obese breast cancer survivors are at increased risk of cancer recurrence and have higher all-cause mortality. Obesity has an impact on breast cancer survivor's quality of life (QOL) and increases the risk of longer-term morbidities such as type 2 diabetes mellitus and cardiovascular disease. Many cancer guidelines recommend survivors maintain a healthy weight but there is a lack of evidence regarding which weight loss method to recommend. OBJECTIVES: To assess the effects of different body weight loss approaches in breast cancer survivors who are overweight or obese (body mass index (BMI) ≥ 25 kg/m2). SEARCH METHODS: We carried out a search in the Cochrane Breast Cancer Group's (CBCG's) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6), MEDLINE (2012 to June 2019), Embase (2015 to June 2019), the World Health Organisation International Clinical Trials Registry Platform (WHO ICTRP) and Clinicaltrials.gov on 17 June 2019. We also searched Mainland Chinese academic literature databases (CNKI), VIP, Wan Fang Data and SinoMed on 25 June 2019. We screened references in relevant manuscripts. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials evaluating body weight management for overweight and obese breast cancer survivors (BMI ≥ 25 kg/m2). The aim of the intervention had to be weight loss. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and assessed risk of bias for the included studies, and applied the quality of the evidence using the GRADE approach. Dichotomous outcomes were analysed as proportions using the risk ratio (RR) as the measure of effect. Continuous data were analysed as means with the measure of effect being expressed as the mean differences (MDs) between treatment groups in change from baseline values with 95% confidence intervals (CIs), when all studies reported exactly the same outcomes on the same scale. If similar outcomes were reported on different scales the standardised mean difference (SMD) was used as the measure of effect. Quality of life data and relevant biomarkers were extracted where available. MAIN RESULTS: We included a total of 20 studies (containing 23 intervention-comparisons) and analysed 2028 randomised women. Participants in the experimental groups received weight loss interventions using the core element of dietary changes, either in isolation or in combination with other core elements such as 'diet and exercise', 'diet and psychosocial support' or 'diet, exercise and psychosocial support'. Participants in the controls groups either received usual care, written materials or placebo, or wait-list controls. The duration of interventions ranged from 0.5 months to 24 months. The duration of follow-up ranged from three months to 36 months. There were no time-to-event data available for overall survival, breast cancer recurrence and disease-free survival. There was a relatively small amount of data available for breast cancer recurrence (281 participants from 4 intervention-comparisons with 14 recurrence events; RR 1.95, 95% CI 0.68 to 5.60; low-quality evidence) and the analysis was likely underpowered. Overall, we found low-quality evidence that weight loss interventions for overweight and obese breast cancer survivors resulted in a reduction in body weight (MD: -2.25 kg, 95% CI: -3.19 to -1.3 kg; 21 intervention-comparisons; 1751 women), body mass index (BMI) (MD: -1.08 kg/m2, 95% CI: -1.61 to -0.56 kg/m2; 17 intervention-comparisons; 1353 women), and waist circumference (MD:-1.73 cm, 95% CI: -3.17 to -0.29 cm; 13 intervention-comparisons; 1193 women), and improved overall quality of life (SMD: 0.74; 95% CI: 0.20 to 1.29; 10 intervention-comparisons; 867 women). No increase was seen in adverse events for women in the intervention groups compared to controls (RR 0.94, 95% CI: 0.76 to 1.17; 4 intervention-comparisons; 394 women; high-quality evidence). Subgroup analyses revealed that decreases in body weight, BMI and waist circumference were present in women regardless of their ethnicity and menopausal status. Multimodal weight loss interventions (which referred to 'diet, exercise and psychosocial support') appeared to result in greater reductions in body weight (MD: -2.88 kg, 95% CI: -3.98 to -1.77 kg; 13 intervention-comparisons; 1526 participants), BMI (MD: -1.44 kg/m2, 95% CI: -2.16 to -0.72 kg/m2; 11 studies; 1187 participants) and waist circumference (MD:-1.66 cm, 95% CI: -3.49 to -0.16 cm; 8 intervention-comparisons; 1021 participants) compared to dietary change alone, however the evidence was low quality. AUTHORS' CONCLUSIONS: Weight loss interventions, particularly multimodal interventions (incorporating diet, exercise and psychosocial support), in overweight or obese breast cancer survivors appear to result in decreases in body weight, BMI and waist circumference and improvement in overall quality of life. There was no increase in adverse events. There is a lack of data to determine the impact of weight loss interventions on survival or breast cancer recurrence. This review is based on studies with marked heterogeneity regarding weight loss interventions. Due to the methods used in included studies, there was a high risk of bias regarding blinding of participants and assessors. Further research is required to determine the optimal weight loss intervention and assess the impact of weight loss on survival outcomes. Long-term follow-up in weight loss intervention studies is required to determine if weight changes are sustained beyond the intervention periods.