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The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy. [ABSTRACT FROM AUTHOR]

The patient subsequently developed genital ulcers, and met clinical criteria for Behçet's syndrome (recurrent oral aphthous ulcers, genital ulceration, skin features). B Cutaneous ulcerations demonstrating pathergy (left), periungual lesion (middle), and an ulcerative scalp lesion (right) C-D Immunophenotyping of patient cells demonstrated C increased frequency of CD4-CD8- TCR + T cells (gated on CD3 + TCR / + cells). 1Clinical features of patient with Behçet's syndrome and STAT1 functional testing. In the largest published cohort of STAT1 GOF patients (247 patients), 98% had CMC [[1]], however other clinical symptoms can vary, even with the same variant. [Extracted from the article]

Purpose: Chronic granulomatous disease (CGD) is an innate immune deficiency, primarily affecting the phagocytic compartment, and presenting with a diverse phenotypic spectrum ranging from severe childhood infections to monogenic inflammatory bowel disease. Dihydrorhodamine (DHR) flow cytometry is the standard diagnostic test for CGD, and correlates with NADPH oxidase activity. While there may be genotype correlation with the DHR flow pattern in some patients, in several others, there is no correlation. In such patients, assessment by flow cytometric evaluation of NADPH oxidase-specific (NOX) proteins provides a convenient and rapid means of genetic triage, though immunoblotting has long been used for this purpose. Methods and Results: We describe the clinical utility of the NOX flow cytometry assay through assessment of X-linked and autosomal recessive CGD patients and their first-degree relatives. The assessment of specific NOX proteins was correlated with overall NADPH oxidase function (DHR flow), clinical phenotype and genotype. NOX-specific protein assessment is a valuable adjunct to DHR assessment and genotyping to classify and characterize CGD patients. Conclusions: The atypical clinical presentation of some CGD patients can make genotype–phenotype correlation with DHR flow data challenging. Genetic testing, while useful for confirmation of diagnosis, can take several weeks, and in some patients does not provide a conclusive answer. However, NADPH-oxidase-specific protein flow assessment offers a rapid alternative to identification of the underlying genetic defect in cellular subsets, and can be utilized as a reflex test to an abnormal DHR flow. Further, it can provide insight into correlation between oxidative burst relative to protein expression in granulocytes and monocytes. [ABSTRACT FROM AUTHOR]

Keywords: Chronic granulomatous disease; COVID-19; immunodeficiency EN Chronic granulomatous disease COVID-19 immunodeficiency 23 25 3 02/01/21 20210101 NES 210101 To the Editor: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first discovered in December 2019, has led to an ongoing, unprecedented global pandemic due to coronavirus disease 2019 (COVID-19). The majority of pediatric COVID-19 cases are mild, and while our patient was hospitalized, he recovered without respiratory support, antiviral therapy for SARS-CoV-2 infection, or anti-inflammatory therapy for COVID-19. There are limited studies of COVID-19 in primary immunodeficiency patients, but the effect of immunodeficiencies on COVID-19 risk and how they may lead to enhanced susceptibility or even protection will improve as our understanding of the immunopathogenesis of this infection evolves and clinical cases are described. [Extracted from the article]