Identification of human D lactate dehydrogenase deficiency.

Phenotypic and biochemical categorization of humans with detrimental variants can provide valuable information on gene function. We illustrate this with the identification of two different homozygous variants resulting in enzymatic loss-of-function in LDHD, encoding lactate dehydrogenase D, in two unrelated patients with elevated D-lactate urinary excretion and plasma concentrations. We establish the role of LDHD by demonstrating that LDHD loss-of-function in zebrafish results in increased concentrations of D-lactate.

Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease.

Background: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (T1) cells but is also produced by CD25 regulatory T (Treg) cells.

Objective: We aimed to identify and characterize human intestinal T1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs).

Plasticity of human CD4 T cell subsets.

Human beings are exposed to a variety of different pathogens, which induce tailored immune responses and consequently generate highly diverse populations of pathogen-specific T cells. CD4(+) T cells have a central role in adaptive immunity, since they provide essential help for both cytotoxic T cell- and antibody-mediated responses. In addition, CD4(+) regulatory T cells are required to maintain self-tolerance and to inhibit immune responses that could damage the host.

IL-21 is a central memory T cell-associated cytokine that inhibits the generation of pathogenic Th1/17 effector cells.

IL-21 promotes Th17 differentiation, and Th17 cells that upregulate T-bet, IFN-γ, and GM-CSF drive experimental autoimmune diseases in mice. Anti-IL-21 treatment of autoimmune patients is therefore a therapeutic option, but the role of IL-21 in human T cell differentiation is incompletely understood. IL-21 was produced at high levels by human CD4(+) central memory T cells, suggesting that it is associated with early T cell differentiation.

Metabolic syndrome in 25% of older people with intellectual disability.

Background: Life expectancy of people with intellectual disabilities (IDs) is rapidly normalizing, as are prevalences of age-related cardiovascular disease in this group. We investigated the prevalence of the metabolic syndrome in the older population with ID and associations with patient characteristics.

Methods: Prevalence of the metabolic syndrome, according to National Cholesterol Education Program-Adult Treatment Panel III criteria, was assessed with standardized physical examinations in 470 Dutch adults with ID, aged ≥50 years, who receive residential care from three Dutch care providing organizations.

Prevalence of cardiovascular risk factors in older people with intellectual disability.

The prevalence and correlates of cardiovascular risk factors in older adults with intellectual disability was examined. We conducted a cross-sectional study with 50- to 90-year-old clients (N = 470) of three Dutch intellectual disability care providing organizations and found that healthy behavior was low, with 98.9% of the participants having an unhealthy diet and 68.