Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system

The Effect of Food Allergen Exclusion on the Growth of Saudi Children

With a variety of symptoms that can impede children’s development, food allergies are an important public health concern. With the help of information from the King Fahad Medical City Hospital in Riyadh, we looked at how restricting certain foods affected the growth of Saudi children who had food allergies. An anonymous self-administered questionnaire asking about the individuals’ demographics and their restricted eating habits was completed by 72 children (48 boys and 24 girls) between the ages of 2 and 14. The sensitivity of six allergens (hen eggs, cow milk, fish, wheat, peanuts, and soybeans), anthropometric indices, specific Immunoglobulin E (IgE) levels, and sensitivity were examined. The Statistical Package for Social Science (SPSS), version 26, was used to analyze the data. Chi-square and t-tests were used to examine the relationships between various category variables. According to the findings, most of the mothers of the children were between the ages of 30 and 40 (80.6%), had a college degree (72.3%), were unemployed (59.7%), and had a monthly family income between 5000 and 15,000 SAR (69.4%). Both sexes had specific IgE antibodies for allergens in classes 2 and 3, with boys having noticeably (p ≤ 0.05) higher quantities than girls. While females were more sensitive to fish and peanuts, boys were more likely than girls to show specific IgE sensitivity to egg white, cow milk, wheat, and soybeans. Both sexes’ allergy levels were considerably (p ≤ 0.01) higher in children aged 5.01 to 10 than in other age groups. In terms of classifications of thinness, overweightness, and obesity, boys were slenderer than girls, and a greater percentage of boys than girls were overweight or obese. The exclusion of hen eggs, cow milk, wheat, and peanuts from the diet had a significant and detrimental effect on body mass index (BMI) and height-for-age ratio among children with impaired growth, in contrast to the demographic factors, which had a significant and favorable effect on the growth of other children. In conclusion, restrictions on food allergens impairs growth in Saudi children, particularly boys’ growth

Multiple Family Members With Delayed Cord Separtion and Combined Immunodeficiency With Novel Mutation in IKBKB

BACKGROUND: Inhibitor of kappa kinase 2 (IKK2) deficiency is a recently described combined immunodeficiency. It undermines the nuclear factor-kappa B (NF-κB) activation pathway. METHODS: The clinical and immunological data of four patients diagnosed with combined immunodeficiency (CID) from two related Saudi families were collected. Autozygosity mapping of all available members and whole exome sequencing of the index case were performed to define the genetic etiology. RESULTS: The patients had early onset (2–4 months of age) severe infections caused by viruses, bacteria, mycobacteria, and fungi. They all had hypogammaglobulinemia and low absolute lymphocyte count. Their lymphocytes failed to respond to PHA mitogen stimulation. A novel homozygous non-sense mutation in the IKBKB gene, c.850C>T (p. Arg284*) was identified in the index patient and segregated with the disease in the rest of the family. He underwent hematopoietic stem cell transplantation (HSCT) from a fully matched sibling with no conditioning. The other three patients succumbed to their disease. Interestingly, all patients had delayed umbilical cord separation. CONCLUSION: IKK2 deficiency causes CID with high mortality. Immune reconstitution with HSCT should be considered as early as possible. Delayed umbilical cord separation in CID patients may be a clue to IKK2 deficiency

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Contains fulltext : 204759.pdf (publisher's version ) (Open Access

Additional file 3: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S3. Variants of unknown significance (class 3) and variants in TRAF3 identified in 17 patients suffering from primary immunodeficiencies. (XLSX 11 kb

Additional file 2: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S2. Shows all causative mutations identified in 72 patients from 68 families suffering from primary immunodeficiencies. (XLSX 17 kb

Additional file 4: of Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Table S4. (A) The number of patients with isolated or combined infections, and (B) the number of patients with isolated or combined immunophenotypes, and the percentage for which we have reported a genetic diagnosis. (XLSX 11 kb