Bruton's tyrosine kinase (
) deficiency preferentially eliminates autoreactive B cells while sparing normal humoral responses, but has not been studied in mucosal immunity. Commensal microbes and ...intact BTK signaling have been independently shown to be essential for arthritis development in K/BxN mice. Here, we examine how BTK-mediated signaling interfaces with the gut microbiome.
-deficient K/BxN mice were found to have small Peyer's Patches with reduced germinal center and IgA class-switched B cells. IgA-switched plasma cells in small intestines were reduced, especially in villi of
-deficient mice. IgH CDR3 sequencing showed similar V gene diversity and somatic hypermutation frequency despite
deficiency but showed reduced CDR3 amino acid polarity, suggesting potential qualitative differences in the gut plasma cell repertoire. Small intestinal IgA was low and IgA coating of commensal bacteria was reduced. IgA-seq showed a shift in small intestinal microbes that are normally IgA-coated into the uncoated fraction in
-deficient mice. Overall, this study shows that BTK supports normal intestinal IgA development in response to commensals. This manuscript was previously published as a preprint at: https://www.biorxiv.org/content/10.1101/2021.03.10.434762v2.
Clinical studies demonstrate that acute renal failure (ARF) is associated with increased mortality, which may be due to pulmonary complications. ARF may affect the lung via increased renal production ...or impaired clearance of mediators of lung injury, such as proinflammatory cytokines. Bilateral nephrectomy is a method to examine directly the deleterious systemic effects of absent renal clearance in ARF without the confounding effects that are associated with ischemia-reperfusion injury (e.g., ischemic ARF) or systemic toxicity (e.g., cisplatin-induced ARF). This study contrasts the effects of ischemic ARF and bilateral nephrectomy on serum cytokines and lung injury. It demonstrates that the acute absence of kidney function after both ischemic ARF and bilateral nephrectomy is associated with an increase in multiple serum cytokines, including IL-6 and IL-1beta, and that the cytokine profiles were distinct. Lung injury after ischemic ARF and bilateral nephrectomy was similar and was characterized by pulmonary vascular congestion and neutrophil infiltration. For investigation of the role of proinflammatory cytokines in pulmonary injury after ARF, the anti-inflammatory cytokine IL-10 was administered before bilateral nephrectomy. IL-10 treatment improved pulmonary architecture and was associated with a reduction in inflammatory markers, including bronchoalveolar lavage fluid total protein, pulmonary myeloperoxidase activity (a biochemical marker of neutrophils), and the chemokine macrophage inflammatory protein 2. These data demonstrate for the first time that the acute absence of kidney function results in pulmonary injury independent of renal ischemia and highlight the critical role of the kidney in the maintenance of serum cytokine balance and pulmonary homeostasis.
By adulthood, most males with fragile X syndrome (FXS) require support to navigate day-to-day settings. The present study cross-sectionally: (1) characterized the profile of daily living skills in ...males with FXS and (2) examined associated participant characteristics (i.e., fragile X mental retardation protein FMRP expression, nonverbal cognition, language, autism symptomatology, and anxiety symptomatology) using the Waisman Activities of Daily Living questionnaire. Males with FXS (n = 57, ages 15-23 years) needed more help/support in the areas of domestic and community daily livings skills, than in the area of personal daily living skills. Significant associations were observed between reduced daily living skills and lower nonverbal cognition, receptive language, expressive language, and increased autism symptomatology. Receptive language emerged as the strongest unique predictor of daily living skill performance.
By adulthood, most males with FXS require support to navigate day-to-day settings. The present study cross-sectionally: (1) characterized the profile of daily living skills in males with FXS and (2) ...examined associated participant characteristics (i.e., FMRP expression, nonverbal cognition, language, ASD symptomatology, and anxiety symptomatology) using the Waisman-Activities of Daily Living questionnaire. Males with FXS (n = 57, ages 15 – 23 years) needed more help/support in the areas of domestic and community daily livings skills, than in the area of personal daily living skills. Significant associations were observed between reduced daily living skills and lower nonverbal cognition, receptive language, expressive language, and increased ASD symptomatology. Receptive language emerged as the strongest unique predictor of daily living skill performance.
Background. From January 2014–July 2014, more than 46 000 unaccompanied children (UC) from Central America crossed the US–Mexico border. In June–July, UC aged 9–17 years in 4 shelters and 1 ...processing center in 4 states were hospitalized with acute respiratory illness. We conducted a multistate investigation to interrupt disease transmission. Methods. Medical charts were abstracted for hospitalized UC. Nonhospitalized UC with influenza-like illness were interviewed, and nasopharyngeal and oropharyngeal swabs were collected to detect respiratory pathogens. Nasopharyngeal swabs were used to assess pneumococcal colonization in symptomatic and asymptomatic UC. Pneumococcal blood isolates from hospitalized UC and nasopharyngeal isolates were characterized by serotyping and whole-genome sequencing. Results. Among 15 hospitalized UC, 4 (44%) of 9 tested positive for influenza viruses, and 6 (43%) of 14 with blood cultures grew pneumococcus, all serotype 5. Among 48 nonhospitalized children with influenza-like illness, 1 or more respiratory pathogens were identified in 46 (96%). Among 774 nonhospitalized UC, 185 (24%) yielded pneumococcus, and 70 (38%) were serotype 5. UC transferring through the processing center were more likely to be colonized with serotype 5 (odds ratio, 3.8; 95% confidence interval, 2.1–6.9). Analysis of core pneumococcal genomes detected 2 related, yet independent, clusters. No pneumococcus cases were reported after pneumococcal and influenza immunization campaigns. Conclusions. This respiratory disease outbreak was due to multiple pathogens, including Streptococcus pneumoniae serotype 5 and influenza viruses. Pneumococcal and influenza vaccinations prevented further transmission. Future efforts to prevent similar outbreaks will benefit from use of both vaccines.
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