A De Novo Frameshift Mutation in TNFAIP3 Impairs A20 Deubiquitination Function to Cause Neuropsychiatric Systemic Lupus Erythematosus
ConclusionsThe mutant A20 may play a role in weakening the tight junction of the blood-brain barrier to cause neurologic symptoms. We report a rare variant ofTNFAIP3 in a patient with NPSLE and reveal its autoimmune disease –causing mechanism in both peripheral tissues and the central nervous system. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - October 17, 2019 Category: Allergy & Immunology Source Type: research

Quality of Life of Patients with Wiskott Aldrich Syndrome and X-Linked Thrombocytopenia: a Study of the Primary Immune Deficiency Consortium (PIDTC), Immune Deficiency Foundation, and the Wiskott-Aldrich Foundation
AbstractBackgroundWe undertook a study to determine the impact of Wiskott Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) and their therapies upon the health-related quality of life (HRQOL) of patients and their families.Materials and MethodsWe undertook a survey of patients and their families, who self-identified as having either WAS or XLT. We assessed the PedsQL ™ 4.0, the parent proxy form, and the family impact module. These results were compared with normative data from previously published reports.ResultsSixty-eight patients (29 patients completed both the PedsQL ™ 4.0 and the parent proxy for...
Source: Journal of Clinical Immunology - October 16, 2019 Category: Allergy & Immunology Source Type: research

Management of ADA-Deficient SCID Patient on Adagen During Pregnancy
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - October 16, 2019 Category: Allergy & Immunology Source Type: research

Homozygous Splice ADA2 Gene Mutation Causing ADA-2 Deficiency
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - October 15, 2019 Category: Allergy & Immunology Source Type: research

Editorial, Journal of Clinical Immunology
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - October 15, 2019 Category: Allergy & Immunology Source Type: research

Novel Gain-of-Function Mutation in Stat1 Sumoylation Site Leads to CMC/CID Phenotype Responsive to Ruxolitinib
In conclusion, a mutation in the SUMO consensus site of STAT1 can lead to gain-of-function that is reversible with jakinib treatment. However, full immunocompetence was not restored, suggesting that this treatment strategy might serve well as a bridge to definitive therapy such as hematopoietic stem cell transplant rather than a long-term treatment option. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - September 11, 2019 Category: Allergy & Immunology Source Type: research

Abnormal Newborn Screen in a WHIM Syndrome Infant
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - September 6, 2019 Category: Allergy & Immunology Source Type: research

Unusual Severe Seborrheic Dermatitis in Two Siblings with Autosomal Recessive Chronic Granulomatous Disease
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - September 3, 2019 Category: Allergy & Immunology Source Type: research

Regulatory T Cells: the Many Faces of Foxp3
AbstractRegulatory T (Treg) cells expressing the transcription factor forkhead box P3 (Foxp3) play a requisite role in the maintenance of immunological homeostasis and prevention of peripheral self-tolerance breakdown. Although Foxp3 by itself is neither necessary nor sufficient to specify many aspects of the Treg cell phenotype, its sustained expression in Treg cells is indispensable for their phenotypic stability, metabolic fitness, and regulatory function. In this review, we summarize recent advances in Treg cell biology, with a particular emphasis on the role of Foxp3 as a transcriptional modulator and metabolic gateke...
Source: Journal of Clinical Immunology - September 2, 2019 Category: Allergy & Immunology Source Type: research

Successful Treatment of PAPA Syndrome with Dual Adalimumab and Tacrolimus Therapy
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 30, 2019 Category: Allergy & Immunology Source Type: research

Autosomal Dominant Hyper-IgE Syndrome Without Significantly Elevated IgE
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 29, 2019 Category: Allergy & Immunology Source Type: research

Clinical and Molecular Features of Chronic Granulomatous Disease in Mainland China and a XL-CGD Female Infant Patient After Prenatal Diagnosis
AbstractPurposeChronic granulomatous disease (CGD) is the most common phagocyte defect disease. Here, we describe 114 CGD patients in our center and report a rare female infant with XL-CGD to provide a better understanding of diagnosis, treatment, and prenatal diagnosis of CGD.MethodPatients were diagnosed by DHR-1,2,3 flow cytometry assays and gene analysis. X chromosome inactivation analysis and gp91phox protein test were used for a female infant with XL-CGD.ResultsXL-CGD accounts for the majority of cases in China and results in higher susceptibility to some infections than AR-CGD. The DHR assay can help diagnose CGD qu...
Source: Journal of Clinical Immunology - August 27, 2019 Category: Allergy & Immunology Source Type: research

STK4 Deficiency in a Patient with Immune Complex Glomerulonephritis, Salt-Losing Tubulopathy, and Castleman ’s-Like Disease
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 23, 2019 Category: Allergy & Immunology Source Type: research

A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects
ConclusionPatients with LRBA deficiency may initially be diagnosed as CVID or ALPS in the clinical practice. Progressive decrease in B cells as well as IgG in ALPS-like patients and addition of IBD symptoms in the follow-up should raise the suspicion for LRBA deficiency. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Th cells, and markedly increased effector memory/effector memory RA+ Th cells (TEMRA Th) cells are important for the diagnosis of the patients in addition to clinical features. Analysis of protein by either WB or flow cytometry is required when the clinicians come across es...
Source: Journal of Clinical Immunology - August 20, 2019 Category: Allergy & Immunology Source Type: research

Survey of Infection Control Precautions for Patients with Severe Combined Immune Deficiency
AbstractSevere combined immune deficiency (SCID) is caused by an array of genetic disorders resulting in a diminished adaptive immune system due to impaired T lymphocytes. In these patients, active infection at the time of hematopoietic transplantation has been shown to increase morbidity and mortality. To prevent transmission of infections in SCID patients, standardized infection control precautions should be implemented. An online survey regarding SCID-specific protocols was distributed through several immunodeficiency organizations. Seventy-three responses were obtained, with the majority (55%) of responses from the USA...
Source: Journal of Clinical Immunology - August 20, 2019 Category: Allergy & Immunology Source Type: research

The Phytopathogenic Fungus Pallidocercospora crystallina -Caused Localized Subcutaneous Phaeohyphomycosis in a Patient with a Homozygous Missense CARD9 Mutation
ConclusionLocalized subcutaneous phaeohyphomycosis caused byP. crystallina was reported in a patient with a homozygousCARD9 mutation. Physicians should be aware of the possibility of aCARD9 mutation in seemingly healthy patients with unexplainable phaeohyphomycosis. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 14, 2019 Category: Allergy & Immunology Source Type: research

Autoimmune Lymphoproliferative Syndrome with Cryptococcus Infection
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 11, 2019 Category: Allergy & Immunology Source Type: research

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency
ConclusionOur data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 10, 2019 Category: Allergy & Immunology Source Type: research

Predicting the Occurrence of Variants in RAG1 and RAG2
AbstractWhile widespread genome sequencing ushers in a new era of preventive medicine, the tools for predictive genomics are still lacking. Time and resource limitations mean that human diseases remain uncharacterized because of an inability to predict clinically relevant genetic variants. A strategy of targeting highly conserved protein regions is used commonly in functional studies. However, this benefit is lost for rare diseases where the attributable genes are mostly conserved. An immunological disorder exemplifying this challenge occurs through damaging mutations inRAG1 andRAG2 which presents at an early age with a di...
Source: Journal of Clinical Immunology - August 6, 2019 Category: Allergy & Immunology Source Type: research

Disseminated Mycobacterial Disease in a Patient with 22q11.2 Deletion Syndrome: Case Report and Review of the Literature
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 5, 2019 Category: Allergy & Immunology Source Type: research

Pattern Recognition Molecules of the Lectin Pathway —Screening of Patients with Suspected Immunodeficiency
ConclusionThe results suggest that neither single nor combined deficiencies of LP PRMs are more frequent among patients referred for an immunological evaluation than in healthy individuals. Future studies are needed and should focus on deficiencies of LP PRMs combined with deficiencies in other parts of the immune system. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 3, 2019 Category: Allergy & Immunology Source Type: research

30-Year Review of Pediatric- and Adult-Onset CVID: Clinical Correlates and Prognostic Indicators
This study was approved by an institutional review board.ResultsClinical features and laboratory results for subjects diagnosed with CVID at a pediatric age are similar to those who had adult-onset CVID. However, majority of the deceased subjects (13/18) were at a pediatric age at CVID symptom onset. These subjects had a lower age at mortality, multiple comorbidities, and often depression. The most common cause of death was infection. Lung disease (OR 5,p 
Source: Journal of Clinical Immunology - August 3, 2019 Category: Allergy & Immunology Source Type: research

LINE-1-Mediated Alu Ya5 Insertion Underlying Complete Autosomal Recessive IFN- γR1 Deficiency
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 3, 2019 Category: Allergy & Immunology Source Type: research

Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT
ConclusionsIn this cohort, allogeneic HCT was curative for CGD-associated IBD. IBD should not contraindicate HCT, as it does not lead to an increased risk of mortality.This study is registered atclinicaltrials.gov NCT02082353. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - August 2, 2019 Category: Allergy & Immunology Source Type: research

How to Identify Common Variable Immunodeficiency Patients Earlier: General Practice Patterns
ConclusionThe risk of a CVID diagnosis was highly related to both the number of consultations and the character of examinations performed by the GP. CVID should be a differential diagnosis among patients with multiple consultations, especially in patients
Source: Journal of Clinical Immunology - August 1, 2019 Category: Allergy & Immunology Source Type: research

RNASEH2B Related Adult-Onset Interferonopathy
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 31, 2019 Category: Allergy & Immunology Source Type: research

Current Status of the Management of Mendelian Susceptibility to Mycobacterial Disease in Mainland China
ConclusionMSMD is an important cause of BCG infection. Flow cytometric detection of IL12RB1 and IFNGR1 expression is very useful for rapid MSMD diagnosis. rhIFN- γ therapy is effective in patients with MSMD, particularly improving prognosis in those with IL12RB1 deficiency. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 31, 2019 Category: Allergy & Immunology Source Type: research

In Memoriam: Prof. Dr. J.M.J.J. Vossen (1937 –2019)
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 25, 2019 Category: Allergy & Immunology Source Type: research

Novel Exonic Deletions in TTC7A in a Newborn with Multiple Intestinal Atresia and Combined Immunodeficiency
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 24, 2019 Category: Allergy & Immunology Source Type: research

Myriad Faces of Chronic Granulomatous Disease: All in an Indian Family with Novel CYBB Defect
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 23, 2019 Category: Allergy & Immunology Source Type: research

WHIM Syndrome: from Pathogenesis Towards Personalized Medicine and Cure
AbstractWHIM syndrome is a rare combined primary immunodeficiency disease named by acronym for the diagnostic tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow; monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. WHIM syndrome is usually caused by autosomal dominant mutations in the G protein-coupled chemokine receptor CXCR4 that impair desensitization, resulting in enhanced and prolonged G protein- and β-arrestin-depe...
Source: Journal of Clinical Immunology - July 16, 2019 Category: Allergy & Immunology Source Type: research

Chronic Mucocutaneous Candidiasis in an Adolescent Boy Due to a Novel Mutation in TRAF3IP2
ConclusionWe describe an adolescent boy with recurrent oral candidiasis and bronchiectasis due to a novel mutation inTRAF3IP2 gene, not reported to date. This is also the only second report of CMC due to ACT1 deficiency. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - July 10, 2019 Category: Allergy & Immunology Source Type: research

Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma
We describe a 22-year-old male with a diagnosis of B cell lymphoblastic leukemia followed by Epstein-Barr virus (EBV)-associated diffuse large B cell lymphoma (DLBCL) with compound heterozygous mutations inDOCK8 and normal intracellular DOCK8 protein expression. Here, B cell lymphoblastic leukemia followed by EBV-associated DLBCL led to the discovery of DOCK8 deficiency. For instances of high clinical suspicion despite normal DOCK8 protein expression, additional functional testing is critical to make a diagnosis. Understanding the spectrum of DOCK8 mutants and their phenotypes will improve our understanding of DOCK8 defici...
Source: Journal of Clinical Immunology - July 2, 2019 Category: Allergy & Immunology Source Type: research

Diagnostic Yield of Next Generation Sequencing in Genetically Undiagnosed Patients with Primary Immunodeficiencies: a Systematic Review
DiscussionNGS has the ability to contribute significantly to the identification of molecular mechanisms in PID patients. The diagnostic yield highly depends on population and on the technical circumstances under which NGS is employed. Further research is needed to determine the exact diagnostic yield and clinical implications of NGS in patients with PID. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 28, 2019 Category: Allergy & Immunology Source Type: research

Cellular Defects in CVID Patients with Chronic Lung Disease in the USIDNET Registry
AbstractPurposeChronic lung disease is the most common cause of morbidity and mortality in patients with common variable immunodeficiency (CVID). While biomarkers exist to predict non-infectious complications, the unique features that define CVID patients with chronic lung disease are not well understood.MethodsWe analyzed data from CVID patients from the retrospective USIDNET (United States Immunodeficiency Network) patient database. Patients were categorized into 3 phenotypes for comparison: (1) CVID without chronic lung disease, (2) CVID with bronchiectasis only, and (3) CVID with interstitial lung disease (ILD) with or...
Source: Journal of Clinical Immunology - June 27, 2019 Category: Allergy & Immunology Source Type: research

Successful Allogenic Stem Cell Transplantation in Patients with Inherited CARD9 Deficiency
We report two unrelated patients from Brazil and Morocco with AR CARD9 deficiency, both successfully treated with hematopoietic stem cell transplantation (HSCT). From childhood onward, the patients had invasive dermatophytic disease, which persisted or recurred despite multiple courses of antifungal treatment. Sanger sequencing identified homozygous missense CARD9 variants at the same residue,c.302G>T (p.R101L) in the Brazilian patient andc.301C>T (p.R101C) in the Moroccan patient. At the ages of 25 and 44  years, respectively, they received a HSCT. The first patient received a HLA-matched HSCT from his CARD9-mu...
Source: Journal of Clinical Immunology - June 20, 2019 Category: Allergy & Immunology Source Type: research

Hematopoietic Stem Cell Transplantation in CARD9 Deficiency: Knight in Shining Armor?
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 19, 2019 Category: Allergy & Immunology Source Type: research

Prof. Dr. Beatriz Tavares Costa-Carvalho Obituary
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 18, 2019 Category: Allergy & Immunology Source Type: research

Respiratory Complications in Patients with Hyper IgM Syndrome
ConclusionsRespiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 11, 2019 Category: Allergy & Immunology Source Type: research

Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies
We report the first two cas es of this phenomenon to affect children. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 8, 2019 Category: Allergy & Immunology Source Type: research

Correction to: Life-Threatening Infections Due to Live-Attenuated Vaccines: Early Manifestations of Inborn Errors of Immunity
The original version of this article unfortunately contained mistake in the following sentence in the Abstract. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 7, 2019 Category: Allergy & Immunology Source Type: research

Chronic Granulomatous Disorder –Associated Colitis Can Be Accurately Evaluated with MRI Scans and Fecal Calprotectin Level
AbstractPurposeColitis is a common and serious complication of chronic granulomatous disorder (CGD) and requires assessment. Colonoscopy is invasive and carries risks of serious complication. We therefore assessed non-invasive monitoring via magnetic resonance imaging (MRI). We also evaluated fecal calprotectin (FCP), the Harvey-Bradshaw index (HBI) clinical score, and serum cytokines.MethodsWe recruited 10 patients with CGD (8 males, mean age 29.6  years), scored a modified HBI, and obtained stool for FCP. The following day we took blood for cytokine measurement via Luminex, performed MR enterography (scored by two i...
Source: Journal of Clinical Immunology - June 6, 2019 Category: Allergy & Immunology Source Type: research

Use of TCR α + β + /CD19 + –Depleted Haploidentical Hematopoietic Stem Cell Transplant Is a Viable Option in Patients With Primary Immune Deficiency Without Matched Sibling Donor
AbstractAllogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with primary immune deficiency (PID). Haploidentical donors have historically been associated with higher rates of graft-versus-host disease (GvHD) and graft failure. Use of T cell receptor (TCR) α+β+/CD19+–depleted grafts has resulted in improved haploidentical HSCT outcomes. We sought to evaluate outcomes of TCR α+β+/CD19+–depleted haploidentical HSCT in pediatric patients with PID at a single center in Australia. Specifically, we evaluated immune reconstitution, looking at time to T cell and ...
Source: Journal of Clinical Immunology - June 6, 2019 Category: Allergy & Immunology Source Type: research

iPLA 2 Activation Mediates Granular Exocytosis and Corrects Microbicidal Defects in ROS-Deficient and CGD Human Neutrophils
ConclusionsIn neutrophils, calmodulin-mediated iPLA2 inhibition controls granule and vesicle exocytosis in the phagosome and in the extracellular microenvironment. Relieving iPLA2 inhibition results in increased exocytosis of primary, secondary, and tertiary granules and secretory vesicles with correction of defective intracellular and extracellular microbicidal activity. In CGD patients presenting ROS defective production, this increase in the non-oxidative killing pathway partially corrects their microbicidal defects. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - June 1, 2019 Category: Allergy & Immunology Source Type: research

Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome
ConclusionsWe conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 29, 2019 Category: Allergy & Immunology Source Type: research

Different Phenotypic Presentations of X-Linked Lymphoproliferative Disease in Siblings with Identical Mutations
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 29, 2019 Category: Allergy & Immunology Source Type: research

Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study
ConclusionsIn conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 25, 2019 Category: Allergy & Immunology Source Type: research

Life-Threatening Infections Due to Live-Attenuated Vaccines: Early Manifestations of Inborn Errors of Immunity
AbstractLive-attenuated vaccines (LAVs) can protect humans against 12 viral and three bacterial diseases. By definition, any clinical infection caused by a LAV that is sufficiently severe to require medical intervention attests to an inherited or acquired immunodeficiency that must be diagnosed or identified. Self-healing infections can also result from milder forms of immunodeficiency. We review here the inherited forms of immunodeficiency underlying severe infections of LAVs. Inborn errors of immunity (IEIs) underlying bacille Calmette-Gu érin (BCG), oral poliovirus (OPV), vaccine measles virus (vMeV), and oral ro...
Source: Journal of Clinical Immunology - May 23, 2019 Category: Allergy & Immunology Source Type: research

Autoinflammation Masquerading as Autoimmunity in an Adult with Heterozygous p.E250K PSTPIP1 Mutation
(Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

Role of Allogeneic Hematopoietic Stem Cell Transplant for Chronic Granulomatous Disease (CGD): a Report of the United States Immunodeficiency Network
ConclusionAllogeneic HSCT was associated with reduced infection incidence and improved functional performance, but not with a change in overall survival. Transplant-related survival was elevated in patients undergoing HSCT before 15  years old. Consider HSCT prior to late adolescence in patients with severely diminished reactive oxygen intermediate synthesis, particularly if a matched sibling is available. (Source: Journal of Clinical Immunology)
Source: Journal of Clinical Immunology - May 20, 2019 Category: Allergy & Immunology Source Type: research