Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients With Primary Immunodeficiency

This study shows that mutations affecting the DNA binding domain of IKAROS can impair the interaction with the target DNA sequence thereby preventing heterochromatin and pericentromeric localization (HC-PC) of the protein. Our results also indicate an impairment of pericentromeric localization of IKAROS by overexpression of a truncated variant, caused by an immature stop codon in IKZF1. We also describe an additional variant in TNFSF10, encoding Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL), additionally presented in individuals of Family A. Our results indicate that this variant may impair the TRAIL-induced apoptosis in target cell lines and prohibit the NFκB activation by TRAIL and may act as a modifier in Family A. Introduction Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency with an estimated incidence of 1:50,000–1:25,000. The disease is characterized by recurrent infections, due to a marked decrease in serum IgG commonly in association with reduced IgM and/or IgA. Most CVID-affected individuals have reduced numbers of isotype-switched memory B cells but relative preservation of pre-germinal center B cells (1–3). As a clinically and genetically heterogeneous disorder, CVID has a variable age of onset. In a recent study, an early disease onset (T, c.427C>T, p.Arg143Trp NM_006060.6, rs757521297) in exon 4 of IKZF1, which segregated with the clinical phenotype (Figures 1A,B). The...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

Conclusion: In conclusion, Frey's procedure appears to be a less burdensome surgical procedure. Thus, it could be the first option for management of patients with large pancreatic stone. PMID: 31824884 [PubMed]
Source: Annals of Surgical Treatment and Research - Category: Surgery Tags: Ann Surg Treat Res Source Type: research
We present a case of ovarian lymphoma, in which an ambiguous intraoperative pathologic report led to overtreatment (unnecessary surgery). A 73-yr-old woman with fatigue and low-grade fever was diagnosed as having a left ovarian tumor by imaging modalities. Exploratory laparotomy was carried out to confirm the diagnosis. The frozen tissue sections of the ovarian tumor showed condensed proliferation of atypical round cells accompanied with a few small lymphocytes. The pathologists could not determine whether this tumor was a lymphoma or another malignancy (eg, dysgerminoma). Hence, they reported it to gynecologists who opera...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: PATHOLOGY OF THE UPPER TRACT: CASE REPORTS Source Type: research
             Basel, 13 December 2019 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the Phase III IMspire150 study, in people with previously untreated BRAF V600 mutation-positive advanced melanoma, met its primary endpoint of progression-free survival (PFS). The study showed adding Tecentriq ® (atezolizumab) to Cotellic® (cobimetinib) and Zelboraf® (vemurafenib) helped to reduce the risk of disease worsening or death, compared to placebo plus Cotellic and Zelboraf. A significant and clinically meaningful improvement in PFS was demonstrated in the study. The safety ...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
Whether indigenous or introduced, red deer (Cervus elaphus,left) now roam every continent except Antarctica. Females ( “hinds”) and males (“stags” or “harts”) segregate most of the year into bachelorette and bachelor groups, respectively. In preparation for autumn battles for a harem of hinds, each hart’s antlers (right) start growing in the spring before shedding by end of winter. Harder than bone, their antlers have been fashioned by humans into knives and other tools for thousands of years. Antler carvers learned rather quickly not to discard leftover horn into campfires because...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
Discovered independently in America, France, and Germany in 1831, chloroform was first used as an anesthetic in 1847 in Edinburgh, Scotland. Six years later, in London, chloroform provided obstetric anesthesia for the birth of Queen Victoria ’s eighth child. Although initially the preferred anesthetic of Europeans because of its potency, portability, and pleasant odor, chloroform fell out of favor in the United States due to its anesthetic mortality. By 1881, however, theDanbury News reported anonlethal chloroforming that took place 95 miles east, in Norwich, Connecticut. (Note that clergyman Henry Ward Beecher had h...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
Editor ’s PerspectiveWhat We Already Know about This TopicSepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection for which there is no direct treatmentMesenchymal stromal cells have potent immunomodulatory, proreparative, and regenerative properties and have potential as therapeutics for sepsisMesenchymal stromal cells enhance bacterial killing by augmenting macrophage functionWhat This Article Tells Us That Is NewIn a rat model of fecal peritonitis, human umbilical cord mesenchymal stromal cells improved survival and reduced bacterial load by enhancing peritone...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
Authors: Dalmády S, Kemény L, Antal M, Gyulai R Abstract Introduction: Psoriasis is a chronic autoimmune skin disease with strong genetic background and environmental triggers. Patients with psoriasis and psoriatic arthritis are at greater risk of developing other chronic and potentially severe comorbidities, such as psoriatic arthritis, hyperlipidemia, type 2 diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases or depression. Recently, accumulating epidemiologic, genetic and pathogenetic evidence indicates that psoriasis is also associated with periodontitis, a chronic progressive ...
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research
This study utilised 5-FU-treatment in a model of colitis-associated CRC to develop a pre-clinical setting of intestinal mucositis coincident with manifestation of CRC.Materials/methods: On day 0, female C57BL/6 mice (n = 10/group); (1) saline control, (2) AOM/DSS control, or (3) AOM/DSS + 5-FU were injected with saline or AOM (i.p; 7.4 mg/kg). Groups 2 and 3 underwent cycles of seven days 2%w/v DSS followed by 14 days plain water. After three cycles, 5-FU was administered weekly (i.p; 75 mg/kg) to group 3 for five weeks. Clinical indicators were measured daily and colonoscopy performed at...
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Conclusion: Our study demonstrated the urgent need for improved liver screening, health education regarding risk behavior and improved awareness campaigns on liver disease. Interest of the general population may be presumed as more than 200,000 people accessed our test of their own accord. PMID: 31822163 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
This study was designed to investigate characteristics of the disease to predict recurrence.Methods: We retrospectively analyzed 617 patients that experienced a first AP attack between January 2009 and December 2014. Based on reviews of clinical and follow-up data, we attempted to identify risk factors of recurrence using Cox regression analysis.Results: During a median follow-up of 3.2 years (range 3-72 months), 100(16.2%) of the 617 study subjects experienced one or more episodes of recurrent acute pancreatitis (RAP). Of these 100 patients, 75(75%) experienced one relapse, 12(12%) two relapses, and 13(13%) ...
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
More News: Acute Leukemia | Acute Lymphoblastic Leukemia | Alcoholism | Allergy & Immunology | Argentina Health | Arthritis | Autoimmune Disease | Biology | Burkitt Lymphoma | Cancer & Oncology | Chemistry | Child Development | Children | Chronic Leukemia | Cirrhosis | Databases & Libraries | Dermatitis | Dermatology | France Health | Genetics | Germany Health | Hospitals | Inflammatory Bowel Disease | Laboratory Medicine | Leukemia | Liver | Lymphoma | Men | Milk | Molecular Biology | Netherlands Health | Pancytopenia | Pediatrics | Penicillin | PET Scan | Physics | Pneumonia | Primary Immunodeficiency Disease | Profits and Losses | Respiratory Medicine | Rheumatology | Sinusitis | Stem Cell Therapy | Stem Cells | Study | Thyroiditis | Translocation | UK Health | Urology & Nephrology | Vasculitis | Wheat | Zinc