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Rev Esp Enferm Dig 2022 Jun 24. Epub 2022 Jun 24.

Endoscopy, University of the Ryukyus, Japan.

We herein report a case of common variable immunodeficiency (CVID). Endoscopy with biopsies disclosed duodenal nodularity with villous flattening associated with CVID. CVID-associated enteropathy is briefly discussed. Read More

J Clin Immunol 2022 Jun 23. Epub 2022 Jun 23.

Université de Lille, UFR Médecine, 59000, Lille, France.

As protein-losing enteropathy (PLE) can lead to hypogammaglobulinemia and lymphopenia, and since common variable immunodeficiency (CVID) is associated with digestive complications, we wondered if (1) PLE could occur during CVID and (2) specific features could help determine whether a patient with antibody deficiency has CVID, PLE, or both. Eligible patients were thus classified in 3 groups: CVID + PLE (n = 8), CVID-only (= 19), and PLE-only (n = 13). PLE was diagnosed using fecal clearance of α1-antitrypsin or 111In-labeled albumin. Read More

Cold Spring Harb Mol Case Stud 2022 Jun 22;8(4). Epub 2022 Jun 22.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York 10032, USA.

Vacuolar ATPases (V-ATPases) are large multisubunit proton pumps conserved among all eukaryotic cells that are involved in diverse functions including acidification of membrane-bound intracellular compartments. The gene encodes an accessory subunit of the vacuolar (V)-ATPase protein pump. Pathogenic variants in have been described in association with a congenital disorder of glycosylation (CDG), which are highly variable, but often characterized by immunodeficiency, hepatopathy, and neurologic manifestations. Read More

Front Cell Infect Microbiol 2022 1;12:896823. Epub 2022 Jun 1.

Department of Microbiology, Vestfold Hospital Trust, Tønsberg, Norway.

We report within-host evolution of antibiotic resistance to trimethoprim-sulfamethoxazole and azithromycin in a nontypeable strain from a patient with common variable immunodeficiency (CVID), who received repeated or prolonged treatment with these antibiotics for recurrent respiratory tract infections. Whole-genome sequencing of three longitudinally collected sputum isolates during the period April 2016 to January 2018 revealed persistence of a strain of sequence type 2386. Reduced susceptibility to trimethoprim-sulfamethoxazole in the first two isolates was associated with mutations in genes encoding dihydrofolate reductase ( and its promotor region, dihydropteroate synthase (), and thymidylate synthase (), while subsequent substitution of a single amino acid in dihydropteroate synthase (G225A) rendered high-level resistance in the third isolate from 2018. Read More

Ann Allergy Asthma Immunol 2022 Jun 16. Epub 2022 Jun 16.

Division of Allergy & Immunology and Center for Cancer and Immunology Research, Children's National Hospital, Washington DC; Department of Pediatrics and GW Cancer Center, George Washington University, Washington DC. Electronic address:

Objective: To update clinicians on current evidence regarding the immunogenicity and safety of COVID-19 vaccines in patients with Inborn Errors of Immunity (IEI).

Data Sources: Peer reviewed, published studies in Pubmed, clinical trials listed on clinicaltrial.gov, and professional organization and governmental guidelines. Read More

Front Immunol 2022 31;13:834137. Epub 2022 May 31.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

Common Variable Immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, is frequently associated with severe inflammatory complications that determine its morbidity and mortality. We hypothesize that (HP), a very common worldwide infection, may contribute to the clinical and immune phenotype of CVID. We stratified 41 CVID patients into HP+ (n=26) and HPneg (n=15) groups, according to previous urease breath test and/or gastric biopsies, and compared their clinical manifestations and immune profile evaluated by flow cytometry. Read More

J Med Case Rep 2022 Jun 11;16(1):235. Epub 2022 Jun 11.

Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, 1445613131, Tehran, Iran.

Background: Progressive multifocal leukoencephalopathy is a rare demyelinating disease that is often secondary to lytic destruction of oligodendrocytes and, to a lesser extent, to astrocytes' response to human neurotrophic John Cunningham polyomavirus. Any underlying congenital disorder of primary or secondary immunodeficiency may predispose to virus infection and possible invasion of the brain. We present the first reported case of progressive multifocal leukoencephalopathy due to a mutation in the RAC2 gene. Read More

Scand J Immunol 2022 Jun 8:e13196. Epub 2022 Jun 8.

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Patients with common variable immunodeficiency (CVID) display low antibody levels and associated symptoms, including an increased risk of infections. The causes of CVID are uncertain and likely heterogeneous. The complement system protects against pathogens and plays essential roles in homeostasis and development. Read More

Front Immunol 2022 20;13:864307. Epub 2022 May 20.

Basic and Clinical Immunology, Change affiliation of Ankmalika Abha Gupta to Division of Basic and Clinical Immunology, Irvine, CA, United States.

The role of CD4 T regulatory cells is well established in peripheral tolerance and the pathogenesis of the murine model and human autoimmune diseases. CD4 T regulatory cells (CD4 Tregs) have been investigated in common variable immunodeficiency (CVID). Recently, additional members have been added to the club of regulatory lymphocytes. Read More

Cureus 2022 Jun 2;14(6):e25594. Epub 2022 Jun 2.

Gastroenterology, SG Gastro Care, Coimbatore, IND.

Common variable immunodeficiency (CVID) or acquired hypogammaglobulinemia is one of the common forms of primary immunodeficiency, which primarily affects the respiratory tract, but is often associated with gastrointestinal complications. The pathophysiology is not fully understood, making a diagnosis of CVID difficult. The low levels of IgG and IgA and defective B cells make intravenous immunoglobulin (IVIG) therapy the mainstay of management. Read More

Front Immunol 2022 16;13:878989. Epub 2022 May 16.

Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Background: Atopic dermatitis (AD) affects up to 25% of children and 10% of adults in Western countries. When severe or recurrent infections and exceedingly elevated serum IgE levels occur in AD patients, an inborn error of immunity (IEI) may be suspected. The International Union of Immunological Societies classification lists variants in different genes responsible for so-called Hyper-IgE syndromes. Read More

Medicina (B Aires) 2022 ;82(3):361-369

Unidad Inmunología e Histocompatibilidad, Hospital Dr. Carlos G. Durand, Buenos Aires, Argentina.

Antibody deficiencies (AD) are characterized by low or absent immunoglobulin levels or the inability to develop a specific antibody response. They are classified in primary (PAD) when there is an intrinsic immune defect, or secondary (SAD) to other diseases or drugs. The aim of our study was to review the evolutio n of AD assisted at the Immunology Unit, Hospital Durand between 1982 and 2020, divided into two periods: Period I (1982-2009) and Period II (2010-2020); to evaluate their growth, epidemiologic features and treatment options. Read More

Clin Res Hepatol Gastroenterol 2022 May 22:101956. Epub 2022 May 22.

Gastroenterology Unit, Hospital Universitario Son Llàtzer, Instituto de Investigación Sanitaria de las Islas Baleares (IdISba). Carretera. Manacor Km 4, 07198. Palma de Mallorca, Spain.

Chronic Norovirus infection is particularly challenging in patients with common variable immunodeficiency (CVID) because of their inability to achieve viral clearance and the risk of developing enteropathy leading to intestinal villous atrophy and malabsorption. To date, therapeutic options to eliminate the virus are limited and only ribavirin has been shown to induce viral clearance in norovirus enteropathy associated with CVID. We report a case of a 48-year-old female patient diagnosed with CVID enteropathy possibly related to norovirus infection who failed a ribavirin-based therapy despite dosage optimization through drug plasma level monitoring. Read More

Front Immunol 2022 6;13:864550. Epub 2022 May 6.

Department of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United States.

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Read More

Front Immunol 2022 4;13:830961. Epub 2022 May 4.

Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, United States.

Humans homozygous for inactivating (lipopolysaccharide (LPS)-responsive beige-like anchor) mutations or with compound heterozygous mutations exhibit a spectrum of immune-related pathologies including inflammatory bowel disease (IBD). The cause of this pathology remains undefined. Here we show that disruption of the colon epithelial barrier in LRBA-deficient mice by dextran sulfate sodium (DSS) consumption leads to severe and uniformly lethal colitis. Read More

J Clin Immunol 2022 May 21. Epub 2022 May 21.

Department of Pediatric Research InstituteMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Ras-related C3 botulinum toxin substrate 2 (RAC2) is a GTPase exclusively expressed in hematopoietic cells that acts as a pivotal regulator of several aspects of cell behavior via various cellular processes. RAC2 undergoes a tightly regulated GTP-binding/GTP-hydrolysis cycle, enabling it to function as a molecular switch. Mutations in RAC2 have been identified in 18 patients with different forms of primary immunodeficiency, ranging from phagocyte defects caused by dominant negative mutations to common variable immunodeficiency resulting from autosomal recessive loss-of-function mutations, or severe combined immunodeficiency due to dominant activating gain-of-function mutations. Read More

Front Immunol 2022 3;13:869570. Epub 2022 May 3.

Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Read More

J Clin Immunol 2022 May 19. Epub 2022 May 19.

Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, with heterogeneous clinical presentation. Our goal was to analyze CD8 T cell homeostasis in patients with infection only CVID, compared to those additionally affected by dysregulatory and autoimmune phenomena.

Methods: We used flow and mass cytometry evaluation of peripheral blood of 40 patients with CVID and 17 healthy donors. Read More

J Clin Immunol 2022 May 19. Epub 2022 May 19.

Department of Medicine, Division of Rheumatology, Allergy & Clinical Immunology, University of Florida, Gainesville, FL, USA.

Purpose: Common variable immunodeficiency (CVID) is the most prevalent symptomatic immunodeficiency in adults. Little is known about the manifestations of CVID presenting in older adults. Herein, we performed a phenotypic characterization of patients diagnosed older than age 40. Read More

Front Immunol 2022 29;13:895209. Epub 2022 Apr 29.

Department of Internal Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.

Introduction: SARS-CoV-2 vaccines' effectiveness is not yet clearly known in immunocompromised patients. This study aims to assess the humoral and cellular specific immune response to SARS-CoV-2 vaccines and the predictors of poor response in patients with common variable immunodeficiency (CVID) phenotype and in patients treated with B-cell depletion therapies (BCDT), as well as the safety of these vaccines.

Methods: From March to September 2021, we performed a prospective study of all adult patients who would receive the SARS-CoV-2 vaccination and were previously diagnosed with (i) a CVID syndrome (CVID phenotype group; n=28) or (ii) multiple sclerosis (MS) treated with B-cell depleting therapies three to six months before vaccination (BCD group; n=24). Read More

J Mol Diagn 2022 06 12;24(6):586-599. Epub 2022 May 12.

School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Department of Clinical Immunology and PathWest, Fiona Stanley Hospital, Perth, Western Australia, Australia. Electronic address:

With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Read More

J Clin Med 2022 Apr 20;11(9). Epub 2022 Apr 20.

Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.

Background And Aims: Common variable immunodeficiency (CVID) comprises a group of diseases with heterogeneous clinical and immunological manifestations. Several mutations have been identified in genes encoding proteins essential for immune function. Our aim was to phenotypically and genotypically characterize a patient diagnosed with CVID and study his response to the SARS-CoV-2 vaccine. Read More

Eur J Immunol 2022 May 13. Epub 2022 May 13.

Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Str. dell'Università 12, Parma, 43121, Italy.

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Read More

Allergol Immunopathol (Madr) 2022 1;50(3):101-105. Epub 2022 May 1.

Department of Allergy, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Spain;

Background: Patients with primary antibody deficiencies, such as Common Variable Immunodeficiency (CVID), have some problems to assess immune response after coronavirus disease (COVID) vaccination. Cutaneous delayed-type hypersensitivity (DTH) has the potential to be used as a useful, simple, and cheaper tool to assess T-cell (T lymphocyte) function.

Methods: Seventeen patients with CVID, a rare disease, received two doses of the mRNA-based Pfizer-BioNTech COVID-19 vaccine. Read More

J Family Med Prim Care 2022 Apr 18;11(4):1552-1554. Epub 2022 Mar 18.

Department of Paediatrics, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education and Reasearch (SRIHER), Porur, Chennai, Tamil Nadu, India.

Common variable immunodeficiency is the most common primary immunodeficiency disorder. Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency is categorized as a common variable immunodeficiency associated with autoimmune manifestations and inflammatory bowel diseases. We report a rare case, an adolescent presenting with severe diabetic ketoacidosis (DKA) and acute pancreatitis with multiorgan dysfunction with common variable immunodeficiency (CVID) with homozygous mutation. Read More

Allergy Rhinol (Providence) 2022 Jan-Dec;13:21526575221096044. Epub 2022 Apr 25.

Cleveland Medical Center, University Hospitals, Cleveland, Ohio, USA.

Background: The coronavirus 2019 disease (COVID-19) has infected many individuals worldwide and continues to pose a significant threat to those with weakened immune systems. The data evaluating the clinical outcomes of patients with humoral immunodeficiencies that contract COVID-19 is limited and conflicting.

Objective: To describe the clinical outcomes of COVID-19 infections in patients with primary humoral immunodeficiency and compare results to current literature. Read More

Iran J Allergy Asthma Immunol 2022 Apr 11;21(2):219-227. Epub 2022 Apr 11.

Department of Immunology, Sheikh Khalifa Medical City- Union 71/Purehealth, and Faculty of Medicine, United Arab Emirates University, Al Ain, United Arab Emirates.

LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency caused by a mutation in the LRBA gene. Affected individuals present with a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, splenomegaly, hepatomegaly, and autoimmune cytopenias. Except for hypogammaglobulinemia, the remaining features resemble autoimmune lymphoproliferative syndrome (ALPS). Read More

J Clin Immunol 2022 Apr 29. Epub 2022 Apr 29.

Myeloid Cell Laboratory, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040, Madrid, Spain.

Common variable immunodeficiency disorders (CVID), the most common primary immune deficiency, includes heterogeneous syndromes characterized by hypogammaglobulinemia and impaired antibody responses. CVID patients frequently suffer from recurrent infections and inflammatory conditions. Currently, immunoglobulin replacement therapy (IgRT) is the first-line treatment to prevent infections and aminorate immune alterations in CVID patients. Read More

Front Immunol 2022 11;13:865838. Epub 2022 Apr 11.

Department of Internal Medicine, Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.

Here we describe a novel mutation in the gene encoding IKAROS, as the cause of common variable immunodeficiency (CVID). The identification of the same defect in the gene with manifestations of asymptomatic selective IgA deficiency and chronic ITP in the father and her younger brother, respectively, demonstrates the large variability of this genetic defect in one single family, while living in the same environment with a relatively similar genetic background. As discussed, clinical penetrance of the molecular defects identified by mutations in and other common gene defects in CVID in familial immune-related abnormalities makes genetic testing a necessary step for diagnosis, management, and counseling, as part of the routine immunological workup. Read More

Front Immunol 2022 8;13:881206. Epub 2022 Apr 8.

Immunology Division, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Barcelona Hospital, Barcelona, Spain.

SASH3 is a lymphoid-specific adaptor protein. In a recent study, SASH3 deficiency was described as a novel X-linked combined immunodeficiency with immune dysregulation, associated with impaired TCR signaling and thymocyte survival in humans. The small number of patients reported to date showed recurrent sinopulmonary, cutaneous and mucosal infections, and autoimmune cytopenia. Read More