Interface Gain-of-Function Mutations in TLR7 Cause Systemic and Neuro-inflammatory Disease
AbstractTLR7 recognizes pathogen-derived single-stranded RNA (ssRNA), a function integral to the innate immune response to viral infection. Notably, TLR7 can also recognize self-derived ssRNA, with gain-of-function mutations in human TLR7 recently identified to cause both early-onset systemic lupus erythematosus (SLE) and neuromyelitis optica. Here, we describe two novel mutations in TLR7, F507S and L528I. While the L528I substitution arose de novo, the F507S mutation was present in three individuals from the same family, including a severely affected male, notably given that the TLR7 gene is situated on the X chromosome a...
Source: Journal of Clinical Immunology - February 7, 2024 Category: Allergy & Immunology Source Type: research
High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study
In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients co uld optimize management of this new and alarming complication of SARS-CoV-2 infection. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - February 6, 2024 Category: Allergy & Immunology Source Type: research
Epidermodysplasia Verruciformis in CADINS Disease: Expanding the Phenotype
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - February 5, 2024 Category: Allergy & Immunology Source Type: research
A Rare AIOLOS N160S Variant Causing IEI in Human
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - February 1, 2024 Category: Allergy & Immunology Source Type: research
Impaired STING Activation Due to a Variant in the E3 Ubiquitin Ligase AMFR in a Patient with Severe VZV Infection and Hemophagocytic Lymphohistiocytosis
In conclusion, we describe a novel genetic etiology of severe VZV disease in childhood, also representing the first inborn error of immunity related to a defect in the cGAS-STING pathway. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 26, 2024 Category: Allergy & Immunology Source Type: research
A Novel Homozygous Germline Mutation in Transferrin Receptor 1 (TfR1) Leads to Combined Immunodeficiency and Provides New Insights into Iron-Immunity Axis
AbstractA homozygous missense mutation in the transferrin receptor 1 (TfR1), also known as CD71, leads to a rare inborn error of immunity (IEI) characterized by the impaired lymphocyte activation and proliferation due to defective iron uptake of cells. However, only one causative mutation (c.58T > C, p.Y20H) in theTFRC gene coding for TfR1 has been reported so far. We herein identified a new disease-causing homozygous germline mutation in theTFRC gene (c.64C > T, p.R22W) (referred to as TfR1R22W from now on) in a Turkish patient with combined immunodeficiency (CID). TfR1R22W results in impaired TfR1 inter...
Source: Journal of Clinical Immunology - January 25, 2024 Category: Allergy & Immunology Source Type: research
Role of Skewed X-Chromosome Inactivation in Common Variable Immunodeficiency
In this study, we aimed to assess the role of skewed X-chromosome inactivation (XCI) in CVID. Within our cohort of 131 genetically analyzed CVID patients, we selected female patients with rare variants in CVID-associated genes located on the X-chromosome. Four patients harboring heterozygous variants inBTK (n = 2),CD40LG (n = 1), andIKBKG (n = 1) were included in the study. We assessed XCI status using the HUMARA assay and an NGS-based method to quantify the expression of the 2 alleles in mRNA. Three of the 4 patients (75%) exhibited skewed XCI, and the mutated allele was predominantly expressed in all cases. Patient 1 har...
Source: Journal of Clinical Immunology - January 24, 2024 Category: Allergy & Immunology Source Type: research
Correction to: Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 22, 2024 Category: Allergy & Immunology Source Type: research
Influence of Splenomegaly and Splenectomy on the Immune Cell Profile of Patients with Common Variable Immunodeficiency Disease
ConclusionSplenectomizing CVID patients with splenomegaly restores the absolute circulating lymphocyte count, suggesting that the decreased T cell count in the presence of splenomegaly cannot be used as an exclusive criterion for combined immunodeficiency. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
Management of Atopy with Dupilumab and Omalizumab in CADINS Disease
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. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
Patient-Reported Outcomes and Medical Provider Satisfaction Among Adult and Pediatric Ataxia-Telangiectasia Patients
ConclusionIt was found that a diagnosis of A-T complexly impacts patient PROs, but such data offers the potential for preventative and therapeutic interventions to improve the care of such patients. While most A-T patients and their caregivers feel their primary A-T medical provider has expertise and compassion in addition to being accessible and trustworthy, a significant percentage of study subjects did not agree that their provider was an expert in A-T or overall trustworthy. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers
ConclusionsAIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
Autoantibody-Mediated Depletion of IL-1RA in Still ’s Disease and Potential Impact of IL-1 Targeting Therapies
ConclusionAutoantibodies neutralizing IL-1Ra may represent a novel patho-mechanism in a subgroup of Still ’s disease patients, which is sensitive to high-dose IL-1 blocking therapy. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
Pyrin Inflammasome Activation Defines Colchicine-Responsive SURF Patients from FMF and Other Recurrent Fevers
AbstractSyndrome of undifferentiated recurrent fever (SURF) is characterized by recurrent fevers, a lack of confirmed molecular diagnosis, and a complete or partial response to colchicine. Despite the clinical similarities to familial Mediterranean fever (FMF), the underlying inflammatory mechanisms of SURF are not yet understood. We here analyzed the in vitro activation of the pyrin inflammasome in a cohort of SURF patients compared to FMF and PFAPA patients. Peripheral blood mononuclear cells (PBMC) were collected from SURF (both colchicine-treated and untreated), FMF, PFAPA patients, and healthy donors. PBMC were stimul...
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
The Inborn Errors of Immunity —Virtual Consultation System Platform in Service for the Italian Primary Immunodeficiency Network: Results from the Validation Phase
ConclusionFrom our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. These results may help the functioning of other international platforms for the management of complex cases. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - January 17, 2024 Category: Allergy & Immunology Source Type: research
