Down’s syndrome (DS) presents with a constellation of cardiac, neurocognitive and growth impairments. Individuals with DS are also prone to severe infections and autoimmunity including thyroiditis, type 1 diabetes, coeliac disease and alopecia areata 1 , 2 . Here, to investigate the mechanisms underlying autoimmune susceptibility, we mapped the soluble and cellular immune landscape of individuals with DS. We found a persistent elevation of up to 22 cytokines at steady state (at levels often exceeding those in patients with acute infection) and detected basal cellular activation: chronic IL-6 signalling in CD4 T cells and a high proportion of plasmablasts and CD11c + Tbet high CD21 low B cells (Tbet is also known as TBX21). This subset is known to be autoimmune-prone and displayed even greater autoreactive features in DS including receptors with fewer non-reference nucleotides and higher IGHV4-34 utilization. In vitro, incubation of naive B cells in the plasma of individuals with DS or with IL-6-activated T cells resulted in increased plasmablast differentiation compared with control plasma or unstimulated T cells, respectively. Finally, we detected 365 auto-antibodies in the plasma of individuals with DS, which targeted the gastrointestinal tract, the pancreas, the thyroid, the central nervous system, and the immune system itself. Together, these data point to an autoimmunity-prone state in DS, in which a steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation all contribute to a breach in immune tolerance. Our findings also open therapeutic paths, as we demonstrate that T cell activation is resolved not only with broad immunosuppressants such as Jak inhibitors, but also with the more tailored approach of IL-6 inhibition.
Background Resilience has been shown to be associated with better psychological outcomes and ability to cope with negative and traumatic events in the healthcare setting. Therefore, in this study, we aimed to evaluate resilience and its association with disease activity and health-related quality of life (HRQOL) in children with Systemic Lupus Erythematosus (SLE) and Juvenile Idiopathic Arthritis (JIA). Findings Patients with diagnoses of SLE or JIA were recruited. We collected: demographic data, medical history and physical examination, physician and patient global health assessments, Patient Reported Outcome Measurement Information System questionnaires, Connor Davidson Resilience Scale 10 (CD-RISC 10), Systemic Lupus Erythematosus Disease Activity Index, and clinical Juvenile Arthritis Disease Activity Score 10. Descriptive statistics were calculated, and PROMIS raw scores were converted to T-scores. Spearman’s correlations were performed, with statistical significance set to p < 0.05. 47 study subjects were recruited. The average CD-RISC 10 score in SLE was 24.4, and in JIA was 25.2. In children with SLE, CD-RISC 10 was correlated with disease activity and inversely correlated with anxiety. In children with JIA, resilience was inversely associated with fatigue, and positively correlated with mobility and peer relationships. Conclusions In children with SLE and JIA, resilience is lower than in the general population. Further, our results suggest that interventions to increase resilience may improve the HRQOL of children with rheumatic disease. Ongoing study of the importance of resilience in this population, as well as interventions to increase resilience, will be an important area of future research in children with SLE and JIA.
Health disparities are a significant cause of concern globally and in the United States. Disparities have been additionally highlighted throughout the ongoing COVID-19 pandemic during which populations of color have been the most affected by the disease. Social determinants of health, race, ethnicity, and gender have all contributed to disparate outcomes and disparities spanning all age groups. Multiple socio-ecological factors contribute to disparities and different strategies have been proposed. The purpose of this paper is to provide an overview of disparities in pediatric treatment and outcomes, with a focus on children with endocrine disorders.
Two male patients, who presented at 13.5 and 13.9 years of age with growth failure and short stature, were ultimately diagnosed with isolated growth hormone deficiency (GHD). Patient 1 was first evaluated when his height declined from −0.67 SD to −1.3 SD. He had a peak growth hormone (GH) concentration to GH stimulation test (GHST) of 16.9 ng/mL (16.9 μg/L) and remained untreated. As puberty advanced, his height decreased further to −1.65 SD. A second GHST while his serum testosterone was 79 ng/dL (2.74 nmol/L) had a peak GH of 5.4 ng/mL (5.4 μg/L), consistent with GHD. He was treated with GH for 4.8 years and reached adult height of 180.5 cm (0.57 SD), gaining 2.22 SDS. Patient 2, height −2.63 SD, had an unstimulated peak GH concentration of 19 ng/mL (19 μg/L). As puberty advanced, his height decreased further to −2.96 SD. Repeat peak GH concentration was 9.2 ng/mL (9.2 μg/L) when serum testosterone was 83.9 ng/dL (2.91 nmol/L). GH treatment resulted in rapid increase of height velocity from 1.8 cm/year to 11.3 cm/year in 6 months, consistent with GHD. Both patients demonstrate that GHD may develop over time and cannot be excluded by a single GHST. Longitudinal monitoring of children with poor growth as puberty progresses is essential to uncover GHD.
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