Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
Although intussusception and food allergy are common health problems in childhood, the relation between these two diseases remain obscure. The aim of this study is to investigate the relationship between food allergy and intussusception, and the factors associated with both. Patients diagnosed with intussusception by the Brighton Collaboration Intussusception Working Group criteria were prospectively investigated for food allergy per the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Guideline. They were analyzed per demographic features, clinical, physical and laboratory findings. There were eight (38.1%) patients diagnosed with food allergy, while 13 (61.9%) patients were non-allergic. The mean number of days of presenting symptoms was 1.13 days in the allergy group and 7.85 days in the non-allergy group. The mean number of intussusception attacks was 1.63 in the allergy group while 1 in the non-allergy group (p < 0.05, relative risk (RR) = 2.6). In the allergy group, one (13%) patient was followed up, six (75%) patients were reduced with pneumatic and one (13%) patient reduced manually. In the non-allergy group, four (31%) patients were followed up, six (46%) patients were reduced with pneumotic, one (7%) patient was reduced manually, and resection anastomosis was performed in two (15%) patients. Food allergy is an unrecognized associated factor for intussusception patients, which increases the risk for recurrence. Due to the small patient population, these results should be interpreted with caution.
Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.
Son günlerde ülkemiz ve tüm dünyayı etkisi altına alan COVID-19 pandemisi önemli bir halk sağlığı sorunu olmuştur. Salgında astımlı hastaların da etkilenmesi mümkündür. Bu aşamada hekimlerin astımlı hastalara doğru yaklaşımı astım COVID-19 arasındaki ilişkinin ortaya konması ile sağlanabilir. Şu ana kadar kontol altındaki astımlılar için COVID-19'un için ek risk getirmediği oluşturmadığı bildirilmişti. Ancak yine de astım hastalarının sosyal izolasyon ve kişisel hijyen kurallarına uymalarının sağlanması önemlidir. Yeni bilgiler elde edilinceye kadar astımın mevcut rehberlere göre tedavi edilmesi uygun bir yaklaşımdır.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.