The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Aug 2016
Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder.
Genome-wide association studies have shown a pattern of rare copy number variations and single nucleotide polymorphisms in patients with common variable immunodeficiency disorder (CVID), which was recognizable by a support vector machine (SVM) algorithm. However, rare monogenic causes of CVID might lack such a genetic fingerprint. ⋯ A novel IRFBP2 mutation was identified in a family with autosomal dominant CVID. Transduction experiments suggest that the mutant protein has an effect on B-cell differentiation and is likely a monogenic cause of the family's CVID phenotype. Successful grouping by the SVM algorithm suggests that our family and other subjects with rare immunodeficiency disorders cluster separately and lack the genetic pattern present in polygenic CVID cases.
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J. Allergy Clin. Immunol. · Jul 2016
Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate.
Sensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored. ⋯ This study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP-mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough.
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J. Allergy Clin. Immunol. · Jul 2016
Intranasal triamcinolone use during pregnancy and the risk of adverse pregnancy outcomes.
Intranasal corticosteroid use during pregnancy has increased over the past decade. ⋯ Maternal exposure to intranasal triamcinolone during pregnancy was not associated with the risk of SGA/spontaneous abortions/overall malformations. However, it has been shown to increase the risk of respiratory system defects. Chance finding cannot be ruled out.
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J. Allergy Clin. Immunol. · Jul 2016
Cross-reactivity and tolerability of aztreonam and cephalosporins in subjects with a T cell-mediated hypersensitivity to penicillins.
The few studies performed in adults with T cell-mediated hypersensitivity to penicillins have found a rate of cross-reactivity with cephalosporins ranging from 2.8% to 31.2% and an absence of cross-reactivity with aztreonam. ⋯ These data demonstrate a rate of cross-reactivity between aminopenicillins and aminocephalosporins (ie, cephalexin, cefaclor, and cefadroxil) of around 20%, as well as the absence of cross-reactivity between penicillins and cefuroxime, ceftriaxone, and aztreonam in all subjects with T cell-mediated hypersensitivity to penicillins, almost exclusively aminopenicillins. Therefore these subjects could be treated with cefuroxime, ceftriaxone, and aztreonam. In those who especially require cephalosporin or aztreonam treatment, however, we recommend pretreatment skin tests because negative responses indicate tolerability.
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J. Allergy Clin. Immunol. · Jul 2016
Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study.
Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. ⋯ APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase δ inhibitors are possible treatment options.