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| [Paper Type: Original article] AND [Author: Broides, Arnon] (4) | 29 Mar 2025 |
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- OPEN ACCESS
- Arnon Broides,
- Ronit Gavrieli,
- Jacov Levy,
- Rachel Levy,
- Nurit Hadad,
- Dirk Roos,
- Baruch Wolach, and
- Amit Nahum
Chronic granulomatous disease is a primary immunodeficiency disease caused by a genetic mutation in any of the 5 genes encoding the different components of the Nicotinamide Adenine Dinucleotide Phosphate reduced (NADPH)-Oxidase enzyme complex. Since primary immunodeficiency diseases are considered to be rare diseases, the genetic diagnosis of a certain primary immunodeficiency leads to the reasonable assumption that all patients with the same disease within the same family will have the same genetic mutation. We report 2 patients with chronic granulomatous disease from the same extended consanguineous family who had different genetic causes of their disease. Therefore, it is crucial to obtain a definitive genetic diagnosis of primary immunodeficiency disease even in patients from the same family, where the same genetic diagnosis is presumed to be the cause of the disease.Statement of novelty: Genetic causes of chronic granulomatous disease may be different in patients from the same family. - OPEN ACCESSBackground: Interleukin-12 Receptor β1 (IL-12Rβ1) deficiency causes susceptibility to weakly virulent atypical mycobacteria and Salmonella. Genotype–phenotype correlations are weak and penetrance is not complete. Most of the culture-recovered Salmonella are with the non typhi types.Case report: We describe an 11 year old male patient with IL-12Rβ1 deficiency. He had an erythematous rash resembling Henoch Schonlein Purpura, and initially presented with slightly elevated CRP. Skin biopsy revealed leukocytoclastic vasculitis. Due to lack of evidence of an active infection, positive ANA, and positive direct Coombs test, an autoimmune lupus-like disease was suspected. In conjunction with rash flares, he showed progressively elevated inflammatory markers, chronic anemia, and hypoalbuminemia. Extensive investigations for an infectious etiology were negative, and without isolation of any pathogens. However, the last of a series of abdominal ultrasound examinations revealed enlarged peritoneal and retroperitoneal lymph-nodes, and biopsy yielded slow-growing bacteria, identified as Salmonella typhi. Prolonged treatment with 2 antimicrobial agents resulted in resolution of skin rash and normalization of laboratory results.Conclusions: We describe an IL-12Rβ1 deficient patient with a progressive inflammatory process with a unique immune dermatological manifestation which was probably triggered by an unexpected pathogen, Salmonella typhi. This patient’s case demonstrates the need for invasive procedures to identify an infectious etiology when routine cultures and serology tests are negative.Statement of novelty: In this case report, we describe a unique presentation of infection with Salmonella typhi in a patient with IL-12Rβ1 deficiency, manifesting with bouts of leucocytoclastic vasculitis. We also report in the same patient, recurrent infection with an unusual pathogen, Kocuria kristinae. Both phenomena have not been reported in such constellation, and we believe this to be a useful and important description that could alert physicians, immunologists, and pediatricians alike to such manifestations. Further, it may help in a rapid and successful diagnosis, therefore benefiting such patients.
- OPEN ACCESSNuclear factor kappa B (NFκB) pathway defects are associated with immunodeficiency; however, multiple phenotypes for mutations in genes encoding for NFκB proteins have been reported. We sought to create a database of published mutations in the genes encoding for IKKα and IKKβ and the regulatory subunit IKKγ, also referred to as NFκB essential modulator (NEMO). All published mutations were reviewed. The clinical and laboratory phenotypes were recorded and yearly updates of new mutations and phenotypes will be performed. Multiple immunodeficiency and infectious phenotypes were recorded particularly for patients with NEMO gene mutations. Even patients with the same NEMO mutation tended to have somewhat different phenotypes. In patients with primary immunodeficiency, the clinical phenotype may not direct the clinician to the genetic cause of the disease. Therefore, a comprehensive database will expand our knowledge and enhance the clinician’s ability to predict which gene mutation is the cause of the immunodeficiency. This database can assist clinicians in the diagnoses of patients with specific features of immunodeficiency.Statement of novelty: A comprehensive database of published mutations in the genes encoding for IKKα, IKKβ, and IKKγ was created. This database may aid the clinician in recognizing specific immunodeficiency phenotypes.
- OPEN ACCESS
- Benyamin Rosental,
- Avishai Shemesh,
- Michal Yaron-Mendelson,
- Lauren C. Klein,
- Yona Kodman,
- Jacov Levy,
- Angel Porgador, and
- Arnon Broides
Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetic, immune dysregulation disorder of aberrant hyperactivation of lymphocytes causing inflammation and hemophagocytosis. We report on a 3-month old male who was evaluated for the possibility of FHL because of a positive family history. The patient was asymptomatic; however, levels of the soluble interleukin 2 (IL-2) receptor were elevated and the quantity and function of the natural killer (NK) cells were severely decreased.Methods: Purification of NK cells and evaluation of the cytotoxicity and IFNγ/TNFα secretion of NK cells after IL-2 activation relative to the patient's family members.Results: The patient's NK specific lysis was enhanced compared with his mother, and it was slightly higher than his sister. The IFNγ and TNFα secretion by the patient's NK cells after challenge with target 721 cells or anti-natural cytotoxicity receptors (NKp30 and NKp44) antibodies showed levels that are close to the mother's and sister's NK secretion levels. Owing to a low yield of NK cells from the patient's father the results for his NK cells are incomplete. The patient did not undergo HSCT and continued to be followed. He is now 7 years old and thriving without signs of FHL. His last examination was in August 2012 for functionality of isolated NK cells. The results showed normal cytotoxicity, cytokine secretion, and CD107a up-regulation to the NK cell surface.Conclusion: We propose that NK function assessment in patients with presumed FHL should be performed on isolated NK cell populations. This practice may reduce the number of false-negative results in NK function assays.Statement of novelty: In this case report we show that functional assessment of unpurified NK cells could lead to a false-negative assessment in 1 of the parameters in FHL. Assessment of NK function without NK purification may lead to an erroneous diagnosis of poor NK function.
