Correction to: Disseminated Infectious Disease Caused by Histoplasma capsulatum in an Adult Patient as First Manifestation of Inherited IL-12R β1 Deficiency
We request that the following corrections be made in our article: (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 5, 2020 Category: Allergy & Immunology Source Type: research

Correction to: A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus
Figure 4a in Manuscript ID#JOCI-D-19-00318 has been revised due to the replacement of immunoblot lane of β-catenin by Zo-1 in NHA group. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 30, 2020 Category: Allergy & Immunology Source Type: research

Successful Treatment of Skewed Lyonization Associated with X-Linked CGD in a Female Presenting with Recalcitrant Crohn ’s Disease
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 27, 2020 Category: Allergy & Immunology Source Type: research

Bourgeoning Scientific Research in Down Syndrome
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 25, 2020 Category: Allergy & Immunology Source Type: research

An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency
ConclusionsRTEL1 mutations are associated with significant alterations in immune landscape and can manifest with infantile-onset IBD. A high index of suspicion is required in Ashkenazi Jewish families where the carriage rate of the C.3791G>A variant is high. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 24, 2020 Category: Allergy & Immunology Source Type: research

Disseminated Infectious Disease Caused by Histoplasma capsulatum in an Adult Patient as First Manifestation of Inherited IL-12R β1 Deficiency
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 24, 2020 Category: Allergy & Immunology Source Type: research

Obstetric and Gynecological Care in Patients with STAT3-Deficient Hyper IgE Syndrome
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 21, 2020 Category: Allergy & Immunology Source Type: research

Successful Matched Related Bone Marrow Transplantation in a Patient with Autosomal Dominant Interferon Gamma Receptor 1 Deficiency
ConclusionA successful curative HCT despite persistent, disseminated, nontuberculous mycobacterial infection in a patient with AD-IFN γR1 suggests that this approach, while difficult, may be useful in other patients with otherwise refractory disease. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 21, 2020 Category: Allergy & Immunology Source Type: research

Progressive B Cell Loss in Revertant X-SCID
We report the case of a patient with X-linked severe combined immunodeficiency (X-SCID) who survived for over 20  years without hematopoietic stem cell transplantation (HSCT) because of a somatic reversion mutation. An important feature of this rare case included the strategy to validate the pathogenicity of a variant of theIL2RG gene when the T and B cell lineages comprised only revertant cells. We studied the X-inactivation of sorted T cells from the mother to show that the pathogenic variant was indeed the cause of his SCID. One interesting feature was a progressive loss of B cells over 20  years. CyTOF (...
Source: Journal of Clinical Immunology - July 17, 2020 Category: Allergy & Immunology Source Type: research

Severe Autoinflammatory Manifestations and Antibody Deficiency Due to Novel Hypermorphic PLCG2 Mutations
AbstractAutoinflammatory diseases (AIDs) were first described as clinical disorders characterized by recurrent episodes of seemingly unprovoked sterile inflammation. In the past few years, the identification of novel AIDs expanded their phenotypes toward more complex clinical pictures associating vasculopathy, autoimmunity, or immunodeficiency. Herein, we describe two unrelated patients suffering since the neonatal period from a complex disease mainly characterized by severe sterile inflammation, recurrent bacterial infections, and marked humoral immunodeficiency. Whole-exome sequencing detected a novel, de novo heterozygo...
Source: Journal of Clinical Immunology - July 15, 2020 Category: Allergy & Immunology Source Type: research

A20 Haploinsufficiency Presenting with a Combined Immunodeficiency
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 15, 2020 Category: Allergy & Immunology Source Type: research

Novel NCF2 Mutation Causing Chronic Granulomatous Disease
We describe three patients with a novel c.855G>CNCF2 mutation presenting with diverse clinical phenotype. Two siblings were heterozygous for the novel mutation and for a previously described exon 8 –9 duplication, while a third unrelated patient was homozygous for the novel mutation. Mutation pathogenicity was confirmed by abnormal DHR123 assay and absent p67phox production and by sequencing of cDNA which showed abnormal RNA splicing. Clinically, the homozygous patient presented with suspected early onset interstitial lung disease andNCF2 mutation was found on genetic testing performed in search for surfactant-rel...
Source: Journal of Clinical Immunology - July 14, 2020 Category: Allergy & Immunology Source Type: research

Prediction Model Based on the Combination of Cytokines and Lymphocyte Subsets for Prognosis of SARS-CoV-2 Infection
ConclusionsSignificant increase of cytokines and decrease of lymphocyte subsets are found positively correlated with in-hospital death. A model based on the combination of three markers provides an attractive approach to predict the prognosis of COVID-19. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 13, 2020 Category: Allergy & Immunology Source Type: research

Correction to: 2020 CIS Annual Meeting: Immune Deficiency & amp; Dysregulation North American Conference
The abstract with Submission ID#809896 has been revised due to duplicate title and the missing main author. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 11, 2020 Category: Allergy & Immunology Source Type: research

Immunologic Features in Coronavirus Disease 2019: Functional Exhaustion of T Cells and Cytokine Storm
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 10, 2020 Category: Allergy & Immunology Source Type: research

Concomitant Pyoderma Gangrenosum-like and Amicrobial Pustulosis of the Folds: a Case Report
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 9, 2020 Category: Allergy & Immunology Source Type: research

Late-Onset EBV Susceptibility and Refractory Pure Red Cell Aplasia Revealing DADA2
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 8, 2020 Category: Allergy & Immunology Source Type: research

Deficiency of Adenosine Deaminase 2 (DADA2): Hidden Variants, Reduced Penetrance, and Unusual Inheritance
ConclusionsADA2 pathogenic variants may not be detected by conventional sequencing and genetic testing and may require the incorporation of additional diagnostic methods. A definitive molecular diagnosis is crucial for all family members to make informed treatment decisions. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 8, 2020 Category: Allergy & Immunology Source Type: research

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis
AbstractIsolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3  months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses in...
Source: Journal of Clinical Immunology - July 7, 2020 Category: Allergy & Immunology Source Type: research

Ocular Manifestations of Chronic Granulomatous Disease: First Report of Coats ’ Disease and Literature Review
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 7, 2020 Category: Allergy & Immunology Source Type: research

Inborn Errors of Adaptive Immunity in Down Syndrome
AbstractDown syndrome fits an immunophenotype of combined immunodeficiency with immunodysregulation, manifesting with increased susceptibility to infections, autoimmunity, autoinflammatory diseases, and hematologic malignancies. Qualitative and quantitative alterations in innate and adaptive immunity are found in most individuals with Down syndrome. However, there is substantial heterogeneity and no correlation between immunophenotype and clinical presentation. Previously, it was thought that the immunological changes in Down syndrome were caused by precocious aging. We emphasize in this review that the immune system in Do...
Source: Journal of Clinical Immunology - July 7, 2020 Category: Allergy & Immunology Source Type: research

Haploidentical Hematopoietic Stem Cell Transplantation for XIAP Deficiency: a Single-Center Report
ConclusionsHaploidentical HSCT may be a treatment option for patients with XIAP deficiency who lack a good matched donor. More studies are needed to determine whether modified MAC with reduced toxicity is more suitable for haploidentical transplantation. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 5, 2020 Category: Allergy & Immunology Source Type: research

Poikiloderma with Neutropenia, Clericuzio-Type Accompanied by Loss of Digits Due to Severe Osteomyelitis
AbstractPoikiloderma with neutropenia (PN), Clericuzio-type is a rare autosomal recessively transmitted genodermatosis caused by biallelic mutations in theUSB1 gene and is characterized by early-onset poikiloderma and chronic neutropenia. Nail dystrophy, palmoplantar hyperkeratosis, hypogonadotropic hypogonadism, and recurrent infections can be associated with the disease. Herein, we present a 27-year-old Turkish male patient newly diagnosed as PN, Clericuzio-type after confirmation of a c.531delA (p.His179MetfsX86) homozygous deleterious mutation in exon 5 of theUSB1 gene. The presented case highlights the importance of g...
Source: Journal of Clinical Immunology - July 4, 2020 Category: Allergy & Immunology Source Type: research

Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect
AbstractGenome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family w...
Source: Journal of Clinical Immunology - July 3, 2020 Category: Allergy & Immunology Source Type: research

A 23-Year Follow-Up of a Patient with Gain-of-Function IkB-Alpha Mutation and Stable Full Chimerism After Hematopoietic Stem Cell Transplantation
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 2, 2020 Category: Allergy & Immunology Source Type: research

Treosulfan-Based Conditioning Regimen in Haematopoietic Stem Cell Transplantation with TCR αβ/CD19 Depletion in Nijmegen Breakage Syndrome.
AbstractNijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to malignancies. HSCT appears to cure immunodeficiency, but remains challenging due to limited experience in long-term risks of transplant-associated toxicity and malignancies. Twenty NBS patients received 22 allogeneic HSCTs with TCR αβ/CD19+ graft depletion with fludarabine 150 mg/m2, cyclophosphamide 20 –40 mg/kg and thymoglobulin 5 mg/kg based conditioning regimens (CRs). Twelve patients additionally received low-dose busulfan 4 mg/kg (Bu group) and ...
Source: Journal of Clinical Immunology - June 30, 2020 Category: Allergy & Immunology Source Type: research

Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients
AbstractMendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital condition characterized by a selective predisposition to infections caused by weakly virulent mycobacteria and other types of intra-macrophagic pathogens. The 16 genes associated with MSMD display a considerable level of allelic heterogeneity, accounting for 31 distinct disorders with variable clinical presentations and prognosis. Most of MSMD deficiencies are isolated, referred to as selective susceptibility to mycobacterial diseases. However, other deficiencies are syndromic MSMD, defined by the combination of the mycobacterial infecti...
Source: Journal of Clinical Immunology - June 30, 2020 Category: Allergy & Immunology Source Type: research

Flow Cytometry Identifies Risk Factors and Dynamic Changes in Patients with COVID-19
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 27, 2020 Category: Allergy & Immunology Source Type: research

Prevalence of Immunological Defects in a Cohort of 97 Rubinstein –Taybi Syndrome Patients
The objective of this study was to investigate primary immunode ficiency (PID) and immune dysregulation in an international cohort of patients with RSTS. All published cases of RSTS were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical an d immunological information. Ninety-seven RSTS patients were identified. For 45 patients, we retrieved data from the published reports while for 52 patients, a clinical update was provided. Recurrent or severe infections, autoimmune/autoinflammatory complications, ...
Source: Journal of Clinical Immunology - June 27, 2020 Category: Allergy & Immunology Source Type: research

Successful Artery Embolization in a Patient with Autoimmune Lymphoproliferative Syndrome Associated with Splenic Rupture
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 25, 2020 Category: Allergy & Immunology Source Type: research

The Association of Fetal Thymus Size with Subsequent T Cell Counts in 22q11.2 Deletion Syndrome
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 25, 2020 Category: Allergy & Immunology Source Type: research

Correction to: A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency
The original version of the article contained error regarding the presentation of the institutional authors in the PDF and html versions. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 23, 2020 Category: Allergy & Immunology Source Type: research

Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome
We report high levels of IFN- αR1, IFN-αR2, and IFN-γR2 expression on the surface of monocytes and EBV-transformed-B (EBV-B) cells from studying 45 DS patients. Total and phosphorylated STAT1 (STAT1 and pSTAT1) levels were constitutively high in unstimulated and IFN-α- and IFN-γ-stimulated monocytes from DS patients but low er than those in patients with GOFSTAT1 mutations. Following stimulation with IFN- α or -γ, but not with IL-6 or IL-21, pSTAT1 and IFN-γ activation factor (GAF) DNA-binding activities were significantly higher in the EBV-B cells of DS patients than in cont...
Source: Journal of Clinical Immunology - June 22, 2020 Category: Allergy & Immunology Source Type: research

Everolimus-Induced Remission of Classic Kaposi ’s Sarcoma Secondary to Cryptic Splicing Mediated CTLA4 Haploinsufficiency
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 19, 2020 Category: Allergy & Immunology Source Type: research

Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series
ConclusionThis is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 19, 2020 Category: Allergy & Immunology Source Type: research

The Konya Declaration for Patients with Primary Immunodeficiencies
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 15, 2020 Category: Allergy & Immunology Source Type: research

Proteomic Analysis of the Acid-Insoluble Fraction of Whole Saliva from Patients Affected by Different Forms of Non-histaminergic Angioedema
AbstractWe analyzed by bidimensional electrophoresis the acid-insoluble fraction of saliva from three classes of angioedema patients and a healthy control group, highlighting significant variations of several normalized spot volumes. Characterization of the corresponding proteins was performed by in-gel tryptic digestion of the spots, followed by high-resolution HPLC-ESI-MS/MS analysis of tryptic mixtures. By this strategy, 16 differentially-expressed proteins among two or more groups were identified. We found higher concentration of proteins involved in immune response (interleukin-1 receptor antagonist and annexin A1), a...
Source: Journal of Clinical Immunology - June 10, 2020 Category: Allergy & Immunology Source Type: research

A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma
ConclusionThis report emphasizes the challenges in recognizing PNP deficiency in a patient suffering from SLE. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 8, 2020 Category: Allergy & Immunology Source Type: research

Haploinsufficiency of A20 Due to Novel Mutations in TNFAIP3
In conclusion, clinical manifestations are diverse in patients with HA20, even in those with the sameTNFAIP3 mutation. A20 inhibits the NF- κB pathway and plays a crucial role in the regulation of cell death. Haploinsufficiency of A20 leads to defects in both innate and adaptive immunity. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 8, 2020 Category: Allergy & Immunology Source Type: research

Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients
This study describes different clinical phenotypes and immunological characteristics of 18 LRBA deficiency patients diagnosed from Egypt. T and B lymphocyte subpopulations, LRBA, and cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression were evaluated in resting and stimulated T cells using flow cytometry. Next-generation sequencing was used to identify mutations in theLRBA gene. LRBA deficiency patients had significantly lower B cells and increased percentage of memory T cells. CTLA4 levels were lower in LRBA-deficient T regulatory cells in comparison to healthy donors at resting conditions and significantly incr...
Source: Journal of Clinical Immunology - June 6, 2020 Category: Allergy & Immunology Source Type: research

Whole-Exome Sequencing-Based Approach for Germline Mutations in Patients with Inborn Errors of Immunity
ConclusionsMost of the disease-causing germline mutations were located in the known IEI genes which could be predicted using patients ’ clinical characteristics. These results may be useful when considering appropriate genetic approaches in the clinical setting. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 6, 2020 Category: Allergy & Immunology Source Type: research

Prognostic Value of Blood-Based Inflammatory Biomarkers in Secondary Hemophagocytic Lymphohistiocytosis
ConclusionSome blood-based inflammatory markers, which can be easily and cheaply detected, are significantly associated with the OS of HLH patients. LMR and RPR, superior to NLR, PLR, RDW, can be taken to predict the OS of patients with HLH. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 3, 2020 Category: Allergy & Immunology Source Type: research

Anti-GM-CSF Autoantibodies and Cryptococcus neoformans var. grubii CNS Vasculitis
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 3, 2020 Category: Allergy & Immunology Source Type: research

The Clinical Immunogenomics Research Consortium Australasia (CIRCA): a Distributed Network Model for Genomic Healthcare Delivery
AbstractThe Clinical Immunogenomics Research Consortium Australasia (CIRCA) crowdsources expertise in medicine, genomics, data science, and fundamental biology to diagnose and treat patients with rare inborn errors of immunity. This distributed network model operates free of geographic borders and allows rapid progression through the full research/translation/clinical management pipeline, from initial gene variant discovery, through functional validation, and on to precision mechanism-based treatment of patients throughout Australia and New Zealand. The model is scalable and applicable to other rare diseases where clinical...
Source: Journal of Clinical Immunology - June 1, 2020 Category: Allergy & Immunology Source Type: research

Incidence of SCID in Germany from 2014 to 2015 an ESPED* Survey on Behalf of the API*** Erhebungseinheit f ür Seltene Pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) ** Arbeitsgemeinschaft Pädiatrische Immunologie
ConclusionsSCID is a rare disease with significant mortality. Newborn screening may give the opportunity to improve the prognosis in a significant number of children with SCID. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 26, 2020 Category: Allergy & Immunology Source Type: research

An Update on XMEN Disease
Abstract“X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia” (XMEN) disease is an inborn error of glycosylation and immunity caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. It is a multisystem disease that strongly affects certain immune cells. MAGT1 is now confirmed as a non-catalytic subunit of the oligosaccharyltransferase complex and facilitates Asparagine (N)-linked glycosylation of specific substrates, making XMEN a congenital disorder of glycosylation manifesting as a combined immune deficiency. The clinical disease has var...
Source: Journal of Clinical Immunology - May 26, 2020 Category: Allergy & Immunology Source Type: research

Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy
We present a cohort of patients with therapy refractory HLH referred to our center who were found to have a simultaneous presentation of complement-mediated thrombotic microangiopathy (TMA). Twenty-three patients had therapy refractory HLH (13 primary, 4 EVB-HLH, 6 HLH without known trigger). Sixteen (69.6%) met high-risk TMA criteria. Renal failure requiring renal replacement therapy, severe hypertension, serositis, and gastrointestinal bleeding were documented only in patients with HLH who had concomitant complement-mediated TMA. Patients with HLH and without TMA required ventilator support mainly due to CNS symptoms, wh...
Source: Journal of Clinical Immunology - May 23, 2020 Category: Allergy & Immunology Source Type: research

A New Patient with NOCARH Syndrome Due to CDC42 Defect
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 18, 2020 Category: Allergy & Immunology Source Type: research

A Systematic Review and Meta-regression Analysis on the Impact of Increasing IgG Trough Level on Infection Rates in Primary Immunodeficiency Patients on Intravenous IgG Therapy
AbstractPurposeWe conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment.MethodsSystematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehen...
Source: Journal of Clinical Immunology - May 16, 2020 Category: Allergy & Immunology Source Type: research

The Growing Spectrum of Human Diseases Caused by Inherited CDC42 Mutations
AbstractSeveral recent studies provide valuable new information that expands the spectrum of human disease associated with mutations inCDC42. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 16, 2020 Category: Allergy & Immunology Source Type: research