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Primary immunodeficiencies are rare diseases, characterized by an increased susceptibility to infections. Early diagnosis and appropriate treatment are critical for reducing morbidity and mortality. Given the rarity of these diseases, the awareness of these disorders by physicians is often insufficient, leading to delayed diagnosis and inappropriate treatment which are the major causes of severe long term complications. In an attempt to address and resolve these problems an Italian Network onpmid:17301409 fatcat:pfwotx5rtvhptkzxiwx34w2wqm
more »... imary immunodeficiencies has been established with the aim to increase the awareness of these disorders among physicians and to provide the best clinical assistance to all patients on the national territory.
Aznar-Baranda, J et al 2018 Enhancing the value of care to people: how innovations meet end-users' needs in integrated care contexts. International Journal of Integrated Care, 18(S2): A21, pp. 1-8, DOI: dx.doi.org/10.5334/ijic.s2021 CONFERENCE ABSTRACT Enhancing the value of care to people: how innovations meet end-users' needs in integrated care contextsdoi:10.5334/ijic.s2021 fatcat:r2ag2ctd5vhrflq4rrahis5ftm
Hemophilia A is a heterogeneous hemorrhagic disorder caused by a large number of mutations. Recurrent mutations are rare, except intron 22 and intron 1 inversions. The substitution of a cytosine to a thymine at nucleotide 6046 in F8 gene was identified in a group of Italian patients affected by hemophilia A from a specific region of Northern Italy with a prevalence of 7.6%. This F8 variant was the second most frequent mutation in our cohort, after the intron 22 inversion. The identification ofdoi:10.1002/mgg3.189 pmid:27066508 pmcid:PMC4799873 fatcat:ylzu73awnfekzajsvxjkoxvmmy
more »... he same mutation in a restricted population gets to suppose the existence of a founder effect. Intragenic and extragenic polymorphic markers were tested to assess this assumption. A peculiar haplotype in linkage disequilibrium with this recurrent mutation (c.6046C>T) was identified in 71% of patients, supporting a founder effect. This distinctive haplotype was not identified in a control group (Fisher's exact test, P < 0.0001), coming from the same geographic region. These data strongly suggested the presence of a founder effect, supporting the existence of a single mutation event. Using DMLE+2.3 software and the mathematical approach described by Bengtsson and Thomson, the inferred age of this mutation is supposed to be about 2325 years (95% CI: 904-5081) ago. 152
Extracellular vesicles (EVs) are secreted membranous particles intensively studied for their potential cargo of diagnostic markers. Efficient and cost-effective isolation methods need to be established for the reproducible and high-throughput study of EVs in the clinical practice. We designed the nickel-based isolation (NBI) to rapidly isolate EVs and combined it with newly-designed amplified luminescent proximity homogeneous assay or digital PCR to detect biomarkers of clinical utility. Fromdoi:10.1016/j.ebiom.2019.04.039 pmid:31047861 pmcid:PMC6558028 fatcat:ryboi4ez7vh7jcdo6y5uec32f4
more »... asma of 46 healthy donors, we systematically recovered small EV (~250 nm of mean diameter; ~3 × 1010/ml) and large EV (~560 nm of mean diameter; ~5 × 108/ml) lineages ranging from 50 to 700 nm, which displayed hematopoietic/endothelial cell markers that were also used in spike-in experiments using EVs from tumor cell lines. In retrospective studies, we detected picomolar concentrations of prostate-specific membrane antigen (PSMA) in fractions of EVs isolated from the plasma of prostate cancer patients, discriminating them from control subjects. Directly from oil-encapsulated EVs for digital PCR, we identified somatic BRAF and KRAS mutations circulating in the plasma of metastatic colorectal cancer (CRC) patients, matching 100% of concordance with tissue diagnostics. Importantly, with higher sensitivity and specificity compared with immuno-isolated EVs, we revealed additional somatic alterations in 7% of wild-type CRC cases that were subsequently validated by further inspections in the matched tissue biopsies. We propose NBI-combined approaches as simple, fast, and robust strategies to probe the tumor heterogeneity and contribute to the development of EV-based liquid biopsy studies. FUND: Associazione Italiana per la Ricerca sul Cancro (AIRC), Fondazione Cassa di Risparmio Trento e Rovereto (CARITRO), and the Italian Ministero Istruzione, Università e Ricerca (Miur).
Recombination activating genes 1 and 2 (RAG) proteins are involved in generating diversity of T-and B-cell receptors via recombination of variable, diversity, and joining (VDJ) gene segments. RAG mutations can manifest with a variety of clinical presentations. Some patients with near complete RAG deficiency, often due to bi-allelic nonsense or frameshift mutations, develop severe infections within the first year of life and are diagnosed withdoi:10.1016/j.clim.2017.10.012 pmid:29104089 pmcid:PMC5941932 fatcat:h7xwh4yucnhvxijlcyci2vfixu
Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) ordoi:10.1182/bloodadvances.2020002793 pmid:33206964 pmcid:PMC7686904 fatcat:bqvq5xdni5g5ngt3s6dhr3ysgi
more »... lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P < .001), lower severity of neutropenia (P = .03), leukopenia (P < .001), lymphopenia (P < .001) with low B+ (P = .001), increased need of granulocyte colony-stimulating factor (P = .04), and increased frequency of autoimmunity over the disease course (P < .001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P < .001) and lower white blood cell (P < .001) and lymphocyte (P < .001) values, higher occurrence of apthae (P = .008), and a stronger association with autoimmune diseases/markers (P = .001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease.
Susanna Esposito, Angelo Claudio Molinari, Rosamaria Mura, Lucia Dora Notarangelo, Annarita Tagliaferri, and Mario Clerici declare no conflicts of interest related to the present work. ...doi:10.1111/hae.13756 pmid:30990961 pmcid:PMC6850056 fatcat:eubnz5zvrjd2zo5xeaxcuovnzy