248 results match your criteria Immunoglobulin D Deficiency

Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.

Nat Commun 2022 Jun 3;13(1):3107. Epub 2022 Jun 3.

Yabumoto Department of Intractable disease research, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. Read More

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Cyclic Fevers in Adult Diagnosed As Hyperimmunoglobulin D Syndrome.

Cureus 2022 Apr 6;14(4):e23878. Epub 2022 Apr 6.

Rheumatology, Atrium Health Wake Forest Baptist, Winston-Salem, USA.

Hyper immunoglobulin D Syndrome (HIDS) is a rare autosomal recessive disease often presents during infancy. The disease is caused by an abnormal gene that codes for mevalonate kinase (MVK). This results in recurrent fever episodes and gastrointestinal discomfort (including diarrhea, joint pain, and oral sores). Read More

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[Analysis of MVK gene variant in a child with high IgD syndrome caused by mevalonate kinase deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Apr;39(4):413-416

Deparment of Paediatrics, The Third People' s Hospital of Hubei Province, Wuhan, Hubei 430415, China.

Objective: To analyze the clinical and genetic features of a patient with mevalonate kinase deficiency (MKD).

Methods: Whole exome sequencing was carried out for the proband. Candidate variant was verified by Sanger sequencing. Read More

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Homozygous V377I mutation causing mevalonate kinase.

BMJ Case Rep 2022 Apr 6;15(4). Epub 2022 Apr 6.

Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, EPE, Setubal, Portugal.

Hyperimmunoglobulinaemia D syndrome (HIDS) is a rare autosomal recessive disorder caused by mutations in the mevalonate kinase (MVK) gene, located on chromosome 12. The most common mutation identified in MVK gene so far is V377I. Compound heterozygotes that include this variant may exhibit a more severe phenotype of the disease and homozygotes are rarely found in clinical practice probably they express a milder phenotype. Read More

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Experience of Autoimmune and autoinflammatory diseases in a Turkish pediatric cohort with primary immunodeficiencies.

Allergol Immunopathol (Madr) 2021 1;49(6):1-7. Epub 2021 Nov 1.

Department of Pediatric Allergy-Immunology, Faculty of Medicine, Çukurova University, Adana, Turkey.

Background: Primary immunodeficiency diseases (PID) are the diseases characterized by a dysfunction of the immune system. Affected patients share a different phenotype such as chronic infections, allergy, autoimmunity, and autoinflammation.

Methods: In all, 433 children with PID were enrolled in this study. Read More

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February 2022

Class Switch Recombination Defects: impact on B cell maturation and antibody responses.

Clin Immunol 2021 01 1;222:108638. Epub 2020 Dec 1.

University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, WA, USA. Electronic address:

To assess how B cell phenotype analysis correlates with antigen responses in patients with class switch recombination defects (CSRD) we quantified memory B cells by flow-cytometry and immunized CSRD patients with the neoantigen bacteriophage phiX174 (phage). CSRD patients showed uniformly absent or markedly reduced switched memory B cells (IgMIgDCD27). CD40L patients had reduced CD27 memory B cells (both non-switched and switched). Read More

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January 2021

Genetic loss of NFAT2 (NFATc1) impairs B cell development of B1 and B2 B cells.

Cell Immunol 2020 03 28;349:104048. Epub 2020 Jan 28.

Dept. of Hematology, Oncology and Immunology, University Hospital Tübingen, Tübingen, Germany; Dept. of Hematology, Oncology and Immunology, Klinikum Region Hannover, KRH Klinikum Siloah, Hannover, Germany. Electronic address:

NFAT2 activity was shown to be of critical importance in B cell receptor signaling, development and proliferation; however its role in B cell development in the periphery is still not completely understood. We confirmed that NFAT2 deletion leads to impaired B1 B cell development, supported by our finding of limited B1 progenitors in the bone marrow and spleen of NFAT2 deficient mice. Moreover, we show for the first time that loss of NFAT2 increases immature B cells in particular transitional T2 and T3 as well as mature follicular B cells while marginal zone B cells are decreased. Read More

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Immunometabolic function of cholesterol in cardiovascular disease and beyond.

Cardiovasc Res 2019 07;115(9):1393-1407

Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Fédération Hospitalo-Universitaire (FHU) Oncoage, Nice, France.

Inflammation represents the driving feature of many diseases, including atherosclerosis, cancer, autoimmunity and infections. It is now established that metabolic processes shape a proper immune response and within this context the alteration in cellular cholesterol homeostasis has emerged as a culprit of many metabolic abnormalities observed in chronic inflammatory diseases. Cholesterol accumulation supports the inflammatory response of myeloid cells (i. Read More

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Hyper-IgD syndrome in a patient with IgA immunodeficiency.

Clin Exp Rheumatol 2018 Sep-Oct;36(5):934. Epub 2018 Jul 19.

Institute of Infection, Immunity and Inflammation, University of Glasgow, UK; and Rheumatology Department, Army Shared Fund "NIMTS" Hospital, Athens, Greece.

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January 2019

Long-acting FC-fusion rhGH (GX-H9) shows potential for up to twice-monthly administration in GH-deficient adults.

Eur J Endocrinol 2018 Sep 4;179(3):169-179. Epub 2018 Jul 4.

Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objective: Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients.

Design: This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea. Read More

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September 2018

Hyper-immunoglobulin D syndrome with novel mutations in an afebrile infant.

Pediatr Dermatol 2018 Jul 30;35(4):482-485. Epub 2018 Mar 30.

Department of Medicine, Dell Medical School, University of Texas, Austin, TX, USA.

Hyper-immunoglobulin D syndrome is a rare autosomal-recessive autoinflammatory syndrome in which a mevalonate kinase deficiency results due to mutations of the mevalonate kinase gene. We report a case of an Asian male infant who was found to have hyper-immunoglobulin D syndrome in the absence of fever. His skin manifestations included cephalic pustulosis as well recurrent transient and fixed pink plaques and nodules on the face and extremities. Read More

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Metabolic Induction of Trained Immunity through the Mevalonate Pathway.

Cell 2018 01;172(1-2):135-146.e9

Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany. Electronic address:

Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Read More

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January 2018

Altered marginal zone and innate-like B cells in aged senescence-accelerated SAMP8 mice with defective IgG1 responses.

Cell Death Dis 2017 08 17;8(8):e3000. Epub 2017 Aug 17.

Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.

Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19CD45RCD21CD23) and a decrease of naive B cells (CD19IgD), whereas there is an enhancement of a CD19CD45R innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45RCD21CD23CD5CD11b) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice. These changes in aged SAMP8 mice were associated with lower IgG isotype levels, displaying low variable gene usage repertoires of the immunoglobulin heavy chain (V) diversity, with a diminution on IgG1-memory B cells (CD11bGr1CD138IgMIgDCD19CD38IgG1), an increase in T follicular helper (T, CD4CXCR5PD1) cell numbers, and an altered MOMA-1 (metallophilic macrophages) band in primary follicles. Read More

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Metabolic Reprogramming Commits Differentiation of Human CD27IgD B Cells to Plasmablasts or CD27IgD Cells.

J Immunol 2017 07 16;199(2):425-434. Epub 2017 Jun 16.

First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka 807-8555, Japan;

B cells play a crucial role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). However, the relevance of the metabolic pathway in the differentiation of human B cell subsets remains unknown. In this article, we show that the combination of CpG/TLR9 and IFN-α markedly induced the differentiation of CD27IgD unswitched memory B cells into CD27CD38 plasmablasts. Read More

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A 6-year-old girl diagnosed with mevalonate kinase deficiency who had hydrops fetalis and neonatal-onset cholestasis.

Nihon Rinsho Meneki Gakkai Kaishi 2017 ;40(2):131-137

Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital.

We experienced a 6-year-old girl diagnosed with mevalonate kinase deficiency (MKD) who had cholestasis, anemia, and elevated inflammatory markers in neonatal period. She was admitted to our hospital because of fever and elevated inflammatory markers at 5 years 11months of age. Without using antibiotics, the fever and the inflammatory markers were spontaneously resolved. Read More

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September 2017

IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice.

Proc Natl Acad Sci U S A 2017 02 30;114(7):E1196-E1204. Epub 2017 Jan 30.

Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;

Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effector functions. IgD CSR is a rare event, and its regulation is poorly understood. We report that deficiency of 53BP1, a DNA damage-response protein, caused age-dependent overproduction of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymphoid tissues. Read More

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February 2017

Mevalonate kinase deficiency associated with ataxia and retinitis pigmentosa in two brothers with MVK gene mutations.

Ophthalmic Genet 2017 Jul-Aug;38(4):340-344. Epub 2017 Jan 17.

c Institut für Humangenetik , Universität Regensburg , Regensburg , Germany.

Purpose: To report the clinical and molecular genetic findings in two brothers with retinitis pigmentosa (RP) and mevalonate kinase deficiency (MKD).

Methods: The brothers were examined clinically and with fundus autofluorescence, near-infrared autofluorescence, and spectral domain optical coherence tomography. Targeted resequencing was done with a custom designed gene panel containing 78 genes associated with RP. Read More

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December 2017

Endothelial Plasmalemma Vesicle-Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells.

J Immunol 2016 11 14;197(10):3970-3981. Epub 2016 Oct 14.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756;

Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgMIgD B cells in both the spleen and the peritoneal cavity. Read More

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November 2016

Duplex Quantitative PCR Assay for Detection of Haemophilus influenzae That Distinguishes Fucose- and Protein D-Negative Strains.

J Clin Microbiol 2016 09 22;54(9):2380-3. Epub 2016 Jun 22.

School of Paediatrics and Child Health, University of Western Australia, Perth, Australia Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia

We have developed a specific Haemophilus influenzae quantitative PCR (qPCR) that also identifies fucose-negative and protein D-negative strains. Analysis of 100 H. influenzae isolates, 28 Haemophilus haemolyticus isolates, and 14 other bacterial species revealed 100% sensitivity (95% confidence interval [CI], 96% to 100%) and 100% specificity (95% CI, 92% to 100%) for this assay. Read More

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September 2016

Periodic Illness Associated With Epstein-Barr Virus: A New Diagnosis After a 22-Year Follow-up.

Clin Infect Dis 2016 06 29;62(12):1613-4. Epub 2016 Mar 29.

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases.

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Hyperimmunoglobulin D syndrome in an Indian family undiagnosed for 11 years.

Int J Rheum Dis 2017 Dec 1;20(12):2236-2237. Epub 2015 Dec 1.

National Amyloidosis Centre, UCL Medical School, Royal Free Campus, London, UK.

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December 2017

Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to promote airway infection.

J Clin Invest 2015 Oct 31;125(10):3878-90. Epub 2015 Aug 31.

Regulation of neutrophil activity is critical for immune evasion among extracellular pathogens, yet the mechanisms by which many bacteria disrupt phagocyte function remain unclear. Here, we have shown that the respiratory pathogen Streptococcus pneumoniae disables neutrophils by exploiting molecular mimicry to degrade platelet-activating factor (PAF), a host-derived inflammatory phospholipid. Using mass spectrometry and murine upper airway infection models, we demonstrated that phosphorylcholine (ChoP) moieties that are shared by PAF and the bacterial cell wall allow S. Read More

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October 2015

In Silico Prediction of the Effects of Mutations in the Human Mevalonate Kinase Gene: Towards a Predictive Framework for Mevalonate Kinase Deficiency.

Ann Hum Genet 2015 Nov 29;79(6):451-9. Epub 2015 Sep 29.

School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK.

Mevalonate kinase (MVK) catalyses the phosphorylation of mevalonate. Deficiency of MVK is associated with two rare periodic fever syndromes, mevalonic aciduria (MA), a severe form and hyper-immunoglobulin-D syndrome (HIDS), a milder form. An in silico approach was used to analyse the physicochemical and structural effects of 47 disease-associated variants of MVK. Read More

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November 2015

A restrospective survey of patients's journey before the diagnosis of mevalonate kinase deficiency.

Joint Bone Spine 2015 Jul 9;82(4):240-4. Epub 2015 Feb 9.

Department of Pediatric Rheumatology, National referral centre for auto-inflammatory diseases (CEREMAI), CHU de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France; University of Paris Sud, Le Kremlin-Bicêtre, France; Inserm U1018 CESP, Le Kremlin-Bicêtre, France.

Unlabelled: Mevalonate kinase deficiency (MKD) is an autosomic recessive auto-inflammatory disease caused by mutations of the MVK gene. MKD being a very rare disease, numerous misdiagnoses and medical referrals may precede the right diagnosis, amplifying the burden of the disease.

Objectives: To evaluate the patient's medical referrals between the first symptom and the diagnosis of MKD and the diagnosis delay. Read More

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Comment to Santos et al., "hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype".

Gene 2015 Mar 22;559(1):99-101. Epub 2015 Jan 22.

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137 Trieste, Italy. Electronic address:

We performed molecular modeling analysis onto a novel mutation in the gene MVK, described by Santos et al., found to be causative of a severe form of Hyper-IgD/Mevalonate Kinase Deficiency. The mutation p. Read More

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Current advances in the understanding and treatment of mevalonate kinase deficiency.

Int J Immunopathol Pharmacol 2014 Oct-Dec;27(4):491-8

Institute of Pediatrics, Universita’ Cattolica Sacro Cuore, Rome, Italy.

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. Read More

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Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease.

Vaccine 2015 Jan 22;33(2):321-6. Epub 2014 Nov 22.

Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia; Department of Respiratory Medicine, Queensland Children's Medical Research Institute, Royal Children's Hospital, QLD, Australia.

Background: Endobronchial infections related to non-typeable Haemophilus influenzae (NTHi) are common in children and adults with suppurative airway disease such as bronchiectasis and COPD. Impaired cell mediated immune responses to NTHi have been described in these patients. Currently there are no interventions known to correct the deficiency in cell mediated immune responses to NTHi. Read More

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January 2015

Altered serum cytokine signature in common variable immunodeficiency.

J Clin Immunol 2014 Nov 23;34(8):971-8. Epub 2014 Sep 23.

Department of Pathology and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.

Purpose: Common variable immunodeficiency (CVID) is the most frequent form of primary symptomatic hypogammaglobulinemia. CVID patients display a number of abnormalities in lymphocyte subpopulations including chronic T-cell activation and decreased numbers of circulating CD4(+) T cells and NK cells. We and others have recently shown that CVID is associated with increased concentration of soluble CD14 (sCD14) and other factors indicating limited microbial translocation. Read More

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November 2014

The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRβ and IgH allelic exclusion.

J Immunol 2014 Sep 15;193(6):2881-90. Epub 2014 Aug 15.

Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

Coordination of V rearrangements between loci on homologous chromosomes is critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM) protein kinase promotes DNA repair and activates checkpoints to suppress aberrant Ig and TCR rearrangements. In response to RAG cleavage of Igκ loci, ATM inhibits RAG expression and suppresses further Vκ-to-Jκ rearrangements to enforce Igκ allelic exclusion. Read More

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September 2014

Zfp318 regulates IgD expression by abrogating transcription termination within the Ighm/Ighd locus.

J Immunol 2014 Sep 23;193(5):2546-53. Epub 2014 Jul 23.

Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112

The protein Zfp318 is expressed during the transition of naive B cells from an immature to mature state. To evaluate its role in mature B cell functions, a conditional gene deficiency in Zfp318 was created and deleted in bone marrow lineages via Vav-Cre. B cell development was minimally altered in the absence of the protein, although transitional 2 (T2) B cell populations were depressed in the absence of Zfp318. Read More

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September 2014