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[Newborn screening for severe T and B lymphocyte deficiencies in Switzerland].

Rev Med Suisse. 2021 Jan 13;17(720-1):68-76

Authors: Fouriki A, Schnider C, Theodoropoulou K, Pachlopnik J, Hofer M, Candotti F

Abstract
Severe Combined Immunodeficiency (SCID) is one of the most severe forms of Primary Immunodeficiencies (PID) and leads to a potentially fatal course of disease without early and definitive treatment. Adequate management, from the first days of life, can improve the survival and outcome of patients with SCID. This can be achieved through newborn screening (NBS) based on the measurement of T-cell receptor excision circles (TREC). Already present in many countries, this NBS test was introduced in Switzerland in January 2019 on a pilot phase. In addition to the assessment of TRECs, the measurement of kappa recombinant excision circles (KREC) has also been introduced at the same time and allows the identification of severe forms of PID characterized by profound B cell lymphopenia.

PMID: 33443835 [PubMed – as supplied by publisher]

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Successful treatment of severe allergic asthma with omalizumab in a girl with DiGeorge syndrome.

Cent Eur J Immunol. 2020;45(3):361-363

Authors: Jesenak M, Zelieskova M, Repko M, Banovcin P

Abstract
DiGeorge syndrome (DGS) is a primary immunodeficiency disease characterized by multiple clinical features, including congenital heart defects, typical facial appearance, hypocalcemia, and immunodeficiency associated to thymic hypoplasia. A subset of patients with DGS may also have contemporary allergic diseases, possibly in the context of T cell dysregulation. Our work presents an unusual case of DGS in coincidence with severe allergic asthma successfully treated by humanized monoclonal anti-IgE antibody, omalizumab. Biological therapy with omalizumab is indicated as an add-on treatment for poorly controlled asthma in patients with severe persistent allergic asthma aged 6 years and above, who meet strict criteria. While data available from clinical trials suggest that omalizumab is generally well-tolerated, a little is known about its efficacy and tolerability in the context of underlying immunodeficiency. We reported for the first time that omalizumab could be safely effective in treatment of severe allergic asthma in patients with DGS, without modification of immunological parameters.

PMID: 33437191 [PubMed]

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Magnesium in Infectious Diseases in Older People.

Nutrients. 2021 Jan 08;13(1):

Authors: Dominguez LJ, Veronese N, Guerrero-Romero F, Barbagallo M

Abstract
Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.

PMID: 33435521 [PubMed – in process]

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Screening for Genetic Mutations for the Early Diagnosis of Common Variable Immunodeficiency in Children With Refractory Immune Thrombocytopenia: A Retrospective Data Analysis From a Tertiary Children’s Center.

Front Pediatr. 2020;8:595135

Authors: Ma J, Fu L, Gu H, Chen Z, Zhang J, Zhao S, Zhu X, Liu H, Wu R

Abstract
Aim: This study aimed to identify common variable immunodeficiency (CVID) by high-throughput next-generation sequencing (NGS) in children with refractory immune thrombocytopenia (RITP) to facilitate early diagnosis. Methods: CVID-related genetic mutations were explored in patients with RITP during 2016-2019. They were tested consecutively through NGS by the ITP team of the tertiary children hospital in China. An evaluation system was devised based on the phenotype, genetic rule, and serum immunoglobulins (Igs) of all patients with RITP. The patients were divided into highly suspicious, suspicious, and negative groups using the evaluation system. Results: Among 176 patients with RITP, 16 (9.1%) harbored CVID-related genetic mutations: 8 (4.5%) were highly suspicious of CVIDs. Five had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), one in lipopolysaccharide responsive beige-like anchor protein (LRBA), one in nuclear factor kappa-B2 (NF-κB2), and one in caspase recruitment domain11 (CARD11). Others were classified into the suspicious group because the clinical phenotype and pedigree were suggestive, yet insufficient, for diagnosis. Repeated infection existed in all patients. Two had an allergic disease. Positive autoimmune serologies were noted in 62.5%. Five had a definite positive family history. The median serum immunoglobulin (Ig)A, IgG, and IgM levels were 0.3875, 6.14, and 0.522 g/L, respectively. Nearly 85.7% of patients had insufficient serum IgA levels, while 37.5% had low IgG and IgM levels. Conclusions: High-throughput NGS and a thorough review of the medical history are beneficial for the early diagnosis of patients without any significant clinical characteristics, distinguishing them from those with primary pediatric ITP. The cases suspicious of CVID need further investigation and follow-up to avoid deterioration.

PMID: 33425813 [PubMed]

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BCGitis as the primary manifestation of chronic granulomatous disease.

IDCases. 2021;23:e01038

Authors: Khalili N, Mohammadzadeh I, Khalili N, Heredia RJ, Zoghi S, Boztug K, Rezaei N

Abstract
Patients with primary immunodeficiency disease (PID) are not only vulnerable to mycobacterial disease, but are also more likely to develop adverse events following BCG vaccination. These events can range from regional disease (BCGitis) to disseminated disease (BCGosis). Chronic granulomatous disease (CGD), which is characterized by impaired leukocyte phagocytic function, is one of the many inherited PIDs that increase the body’s susceptibility to recurrent bacterial and fungal infections. Here, we report a 6-year-old boy with no significant past medical history who presented with progressive lymphadenopathy six years after BCG vaccination. He was later diagnosed with CGD on further evaluation.

PMID: 33425681 [PubMed]

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