Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study.

BACKGROUND: Physical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour. METHODS: Data from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model. RESULTS: Data of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients' disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3-17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10). CONCLUSIONS: Depending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

A Novel AICDA Splice-Site Mutation in Two Siblings with HIGM2 Permits Somatic Hypermutation but Abrogates Mutational Targeting.

Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance. Herein, we describe two siblings with HIGM2 due to a novel homozygous AICDA mutation (c.428-1G > T) which disrupts the splice acceptor site of exon 4 and results in the sole expression of a truncated AID variant that lacks 10 highly conserved amino acids encoded by exon 4 (AID-ΔE4a). AID-ΔE4a patients suffered from defective CSR and enhanced GC reactions and were therefore indistinguishable from other AR-AID patients. However, the AID-ΔE4a variant only partially affected SHM as observed in AD-AID patients. In addition, AID-ΔE4a but not AD-AID patients revealed impaired targeting of mutational hotspot motives and distorted mutational patterns. Hence, qualitative defects in AID function and altered SHM rather than global decreased SHM activity may account for the disease phenotype in these patients.

Interchangeability of measurements of total and free prostate-specific antigen in serum with 5 frequently used assay combinations: an update.

BACKGROUND: The comparability of total and free prostate-specific antigen (tPSA and fPSA) results among commercial PSA assays has been suggested to be improved by calibration to WHO PSA reference materials and the development of equimolar-response assays. To characterize the current situation, we assessed 5 frequently used commercial assay combinations for tPSA and fPSA regarding the interchangeability of the PSA values and the ratio of fPSA to tPSA (%fPSA), equimolar characteristics, and diagnostic accuracy. METHODS: Sera from 314 patients with prostate cancer (PCa) and 282 men with no evidence of prostate cancer (NPCa) were measured with tPSA and fPSA assays from Abbott (AxSYM), Beckman Coulter (Access), Diagnostic Products Corporation (Immulite 2000), and Roche (Elecsys 2010) and with tPSA and complexed PSA (cPSA) assays from Bayer (ADVIA Centaur). RESULTS: Method comparisons (Passing and Bablok regressions; Bland-Altman plots) showed assay-dependent results for tPSA, fPSA, and %fPSA. With the Access tPSA values taken as 100%, tPSA concentrations varied from 87% (AxSYM and ADVIA Centaur) to 115% (Immulite), leading to different numbers of patients classified according to the commonly recommended tPSA cutoffs for performing a biopsy. Different %fPSA values also led to assay-dependent ROC analysis results, a finding that shows the importance for the diagnostic accuracy. CONCLUSION: Interchangeability of tPSA, fPSA, and %fPSA values obtained by commercial PSA assays remains inadequate, but attention to this issue may minimize the misinterpretation of PSA results obtained by different assays.