Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects.

Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack of well-curated lines from a large array of participants. Answer ALS has generated over 1,000 iPSC lines from control and amyotrophic lateral sclerosis (ALS) patients along with clinical and whole-genome sequencing data. The current report summarizes cell marker and gene expression in motor neuron cultures derived from 92 healthy control and 341 ALS participants using a 32-day differentiation protocol. This is the largest set of iPSCs to be differentiated into motor neurons, and characterization suggests that cell composition and sex are significant sources of variability that need to be carefully controlled for in future studies. These data are reported as a resource for the scientific community that will utilize Answer ALS data for disease modeling using a wider array of omics being made available for these samples.

Control of allergic rhinitis in four latin american countries: Rinola study.

Background: Allergic rhinitis (AR) affects up to 40% of the general population, there are large-scale multicenter studies that have described its characteristics and few studies have focused on studying patients with AR in Latin America (LA). Methodology: A cross-sectional, descriptive, multicenter study was carried out in four LA countries (Colombia, Argentina, Cuba and Peru). Patients diagnosed with AR between November 2017 and June 2020 were included. Sociodemographic and clinical data, sensitization profile and current treatment were collected in the Electronic Data Collection (BDClinic). Patients also filled out this questionnaires: Rhinitis Control Assessment Test (RCAT), Reflexive Total Nasal Symptom Score (rTNSS), Modified ARIA Criteria for AR Severity (mARIA) and ESPRINT-15. Risk of bias was examined by applying the STROBE checklist. Results: The study included 412 patients. Median age was 25 years (15-39). Two hundred and twenty four (54.3%) were women. Nasal obstruction was present in 303 (73.5%). Three hundred and thirty four (81%) had a persistent AR. One hundred and twenty one (31.3%) had associated asthma. The most frequently positive skin tests were: Dermatophagoides pteronyssinus in 365 (88.6%) and Dermatophagoides farinae in 331 (81.3%). Four hundred and eleven patients (99%) reported that AR affected their quality of life. The median score of ESPRINT-15 was 1.87 (0.93-2.93), The mean values of RCAT and rTNSS were 19.01 (±4.59) and 5.4 (±2.97) respectively. Two hundred and fifty (60%) were receiving only oral antihistamines. Physicians decided to start nasal corticosteroids in 296 (71.8%). Only seventy patients (16.9%) were receiving immunotherapy. Conclusion: These findings confirm that most of patients with AR in LA have a persistent disease with a negative impact on quality of life. Dust mites are the main sensitizers. These findings will allow to know the true impact of AR and can lead to a better disease management.

C9orf72 in myeloid cells suppresses STING-induced inflammation.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that overlap in their clinical presentation, pathology and genetic origin. Autoimmune disorders are also overrepresented in both ALS and FTD, but this remains an unexplained epidemiologic observation1-3. Expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial ALS and FTD (C9-ALS/FTD), and lead to both repeat-containing RNA and dipeptide accumulation, coupled with decreased C9orf72 protein expression in brain and peripheral blood cells4-6. Here we show in mice that loss of C9orf72 from myeloid cells alone is sufficient to recapitulate the age-dependent lymphoid hypertrophy and autoinflammation seen in animals with a complete knockout of C9orf72. Dendritic cells isolated from C9orf72-/- mice show marked early activation of the type I interferon response, and C9orf72-/- myeloid cells are selectively hyperresponsive to activators of the stimulator of interferon genes (STING) protein-a key regulator of the innate immune response to cytosolic DNA. Degradation of STING through the autolysosomal pathway is diminished in C9orf72-/- myeloid cells, and blocking STING suppresses hyperactive type I interferon responses in C9orf72-/- immune cells as well as splenomegaly and inflammation in C9orf72-/- mice. Moreover, mice lacking one or both copies of C9orf72 are more susceptible to experimental autoimmune encephalitis, mirroring the susceptibility to autoimmune diseases seen in people with C9-ALS/FTD. Finally, blood-derived macrophages, whole blood and brain tissue from patients with C9-ALS/FTD all show an elevated type I interferon signature compared with samples from people with sporadic ALS/FTD; this increased interferon response can be suppressed with a STING inhibitor. Collectively, our results suggest that patients with C9-ALS/FTD have an altered immunophenotype because their reduced levels of C9orf72 cannot suppress the inflammation mediated by the induction of type I interferons by STING.