Clinical, Immunological, and Molecular Heterogeneity of 173 Patients With the Phenotype of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome.

Abstract:

:Background: Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) Syndrome is a rare recessive disorder caused by mutations in the FOXP3 gene. In addition, there has been an increasing number of patients with wild-type FOXP3 gene and, in some cases, mutations in other immune regulatory genes. Objective: To molecularly asses a cohort of 173 patients with the IPEX phenotype and to delineate the relationship between the clinical/immunologic phenotypes and the genotypes. Methods: We reviewed the clinical presentation and laboratory characteristics of each patient and compared clinical and laboratory data of FOXP3 mutation-positive (IPEX patients) with those from FOXP3 mutation-negative patients (IPEX-like). A total of 173 affected patients underwent direct sequence analysis of the FOXP3 gene while 85 IPEX-like patients with normal FOXP3 were investigated by a multiplex panel of "Primary Immune Deficiency (PID-related) genes." Results: Forty-four distinct FOXP3 variants were identified in 88 IPEX patients, 9 of which were not previously reported. Among the 85 IPEX-like patients, 19 different disease-associated variants affecting 9 distinct genes were identified. Conclusions: We provide a comprehensive analysis of the clinical features and molecular bases of IPEX and IPEX-like patients. Although we were not able to identify major distinctive clinical features to differentiate IPEX from IPEX-like syndromes, we propose a simple flow-chart to effectively evaluate such patients and to focus on the most likely molecular diagnosis. Given the large number of potential candidate genes and overlapping phenotypes, selecting a panel of PID-related genes will facilitate a molecular diagnosis.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Gambineri E,Ciullini Mannurita S,Hagin D,Vignoli M,Anover-Sombke S,DeBoer S,Segundo GRS,Allenspach EJ,Favre C,Ochs HD,Torgerson TR

doi

10.3389/fimmu.2018.02411

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

2411

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • Features of Immunosenescence in Women Newly Diagnosed With Breast Cancer.

    abstract::Adults exposed to childhood maltreatment have increased stress reactivity. This profile is associated with dysregulation of the immune system, including enhanced inflammatory reactions and accelerated senescence. Subjects exposed to ear stress have increased risk for several age-related diseases, including cardiovascu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01651

    authors: Trintinaglia L,Bandinelli LP,Grassi-Oliveira R,Petersen LE,Anzolin M,Correa BL,Schuch JB,Bauer ME

    更新日期:2018-07-16 00:00:00

  • Are Conventional Type 1 Dendritic Cells Critical for Protective Antitumor Immunity and How?

    abstract::Dendritic cells (DCs) are endowed with a unique potency to prime T cells, as well as to orchestrate their expansion, functional polarization and effector activity in non-lymphoid tissues or in their draining lymph nodes. The concept of harnessing DC immunogenicity to induce protective responses in cancer patients was ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00009

    authors: Cancel JC,Crozat K,Dalod M,Mattiuz R

    更新日期:2019-02-12 00:00:00

  • IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction.

    abstract::Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,随机对照试验

    doi:10.3389/fimmu.2018.02035

    authors: Orrem HL,Nilsson PH,Pischke SE,Kleveland O,Yndestad A,Ekholt K,Damås JK,Espevik T,Bendz B,Halvorsen B,Gregersen I,Wiseth R,Andersen GØ,Ueland T,Gullestad L,Aukrust P,Barratt-Due A,Mollnes TE

    更新日期:2018-09-12 00:00:00

  • Individual in vivo Profiles of Microglia Polarization After Stroke, Represented by the Genes iNOS and Ym1.

    abstract::Microglia are the brain-innate immune cells which actively surveil their environment and mediate multiple aspects of neuroinflammation, due to their ability to acquire diverse activation states and phenotypes. Simplified, M1-like microglia are defined as pro-inflammatory cells, while the alternative M2-like cells prom...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01236

    authors: Collmann FM,Pijnenburg R,Hamzei-Taj S,Minassian A,Folz-Donahue K,Kukat C,Aswendt M,Hoehn M

    更新日期:2019-06-04 00:00:00

  • CD4+ T Cells Play a Critical Role in Microbiota-Maintained Anti-HBV Immunity in a Mouse Model.

    abstract::The ability of the host to clear hepatitis B virus (HBV) is closely correlated to the establishment of commensal microbiota. However, how microbiota affects anti-HBV immunity is still unclear. Using a well-known hydrodynamical HBV transfection mouse model and treatment with antibiotics (Atb), we explored the change in...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00927

    authors: Wu T,Li F,Chen Y,Wei H,Tian Z,Sun C,Sun R

    更新日期:2019-04-30 00:00:00

  • Pro-Inflammatory Signaling by IL-10 and IL-22: Bad Habit Stirred Up by Interferons?

    abstract::Interleukin (IL)-10 and IL-22 are key members of the IL-10 cytokine family that share characteristic properties such as defined structural features, usage of IL-10R2 as one receptor chain, and activation of signal transducer and activator of transcription (STAT)-3 as dominant signaling mode. IL-10, formerly known as c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2013.00018

    authors: Mühl H

    更新日期:2013-02-04 00:00:00

  • Remote Activation of a Latent Epitope in an Autoantigen Decoded With Simulated B-Factors.

    abstract::Mutants of a catalytically inactive variant of Proteinase 3 (PR3)-iPR3-Val103 possessing a Ser195Ala mutation relative to wild-type PR3-Val103-offer insights into how autoantigen PR3 interacts with antineutrophil cytoplasmic antibodies (ANCAs) in granulomatosis with polyangiitis (GPA) and whether such interactions can...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02467

    authors: Pang YP,Casal Moura M,Thompson GE,Nelson DR,Hummel AM,Jenne DE,Emerling D,Volkmuth W,Robinson WH,Specks U

    更新日期:2019-10-25 00:00:00

  • Cell-Free Mitochondrial DNA in the CSF: A Potential Prognostic Biomarker of Anti-NMDAR Encephalitis.

    abstract::Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory brain disease that can develop a variety of neuropsychiatric presentations. However, the underlying nature of its inflammatory neuronal injury remains unclear. Mitochondrial DNA (mtDNA) is recently regarded as a damage-associated mol...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00103

    authors: Peng Y,Zheng D,Zhang X,Pan S,Ji T,Zhang J,Shen HY,Wang HH

    更新日期:2019-02-06 00:00:00

  • Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differential Regulation and Correlation With Disease Activity.

    abstract::Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.03057

    authors: Mendez-Huergo SP,Hockl PF,Stupirski JC,Maller SM,Morosi LG,Pinto NA,Berón AM,Musuruana JL,Nasswetter GG,Cavallasca JA,Rabinovich GA

    更新日期:2019-01-09 00:00:00

  • MicroRNA-21: A Positive Regulator for Optimal Production of Type I and Type III Interferon by Plasmacytoid Dendritic Cells.

    abstract::Plasmacytoid dendritic cells (pDCs) are the major producers of type I and type III interferons (IFNs) that play essential roles in host antiviral immunity. MicroRNAs (miRs) are small, noncoding RNAs that can modulate many immune processes. Although molecular regulation of type I IFN production by pDCs has been studied...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00947

    authors: Liu F,Liu C,Hu X,Shang Y,Wu L

    更新日期:2017-08-21 00:00:00

  • Vaccination with Altered Peptide Ligands of a Plasmodium berghei Circumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes.

    abstract::Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell ep...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00115

    authors: Minigo G,Flanagan KL,Slattery RM,Plebanski M

    更新日期:2017-02-14 00:00:00

  • Post-Aire maturation of thymic medullary epithelial cells involves selective expression of keratinocyte-specific autoantigens.

    abstract::The autoimmune regulator (Aire)-directed ectopic expression of tissue-specific antigens (TSAs) by mature medullary thymic epithelial cells (mTECs) has been viewed as an essential mechanism in the induction of central tolerance. Recent data suggest that the survival of mTECs extends beyond the Aire+ cell population to ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00019

    authors: Wang X,Laan M,Bichele R,Kisand K,Scott HS,Peterson P

    更新日期:2012-03-01 00:00:00

  • Histone Deacetylase 1 Plays an Acetylation-Independent Role in Influenza A Virus Replication.

    abstract::Influenza A viruses (IAVs) take advantage of the host acetylation system for their own benefit. Whether the nucleoprotein (NP) of IAVs undergoes acetylation and the interaction between the NP and the class I histone deacetylases (HDACs) were largely unknown. Here, we showed that the NP protein of IAV interacted with H...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01757

    authors: Chen L,Wang C,Luo J,Su W,Li M,Zhao N,Lyu W,Attaran H,He Y,Ding H,He H

    更新日期:2017-12-12 00:00:00

  • Early Ovariectomy Results in Reduced Numbers of CD11c+/CD11b+ Spleen Cells and Impacts Disease Expression in Murine Lupus.

    abstract::Ninety percent of those diagnosed with systemic lupus erythematosus are female, with peak incidence between the ages of 15 and 45, when women are most hormonally active. Despite significant research effort, the mechanisms underlying this sex bias remain unclear. We previously showed that a functional knockout of estro...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00031

    authors: Cunningham MA,Wirth JR,Scott JL,Eudaly J,Collins EL,Gilkeson GS

    更新日期:2016-02-15 00:00:00

  • Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity.

    abstract:OBJECTIVE:Roseburia hominis is a flagellated gut anaerobic bacterium belonging to the Lachnospiraceae family within the Firmicutes phylum. A significant decrease of R. hominis colonization in the gut of ulcerative colitis patients has recently been demonstrated. In this work, we have investigated the mechanisms of R. h...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01166

    authors: Patterson AM,Mulder IE,Travis AJ,Lan A,Cerf-Bensussan N,Gaboriau-Routhiau V,Garden K,Logan E,Delday MI,Coutts AGP,Monnais E,Ferraria VC,Inoue R,Grant G,Aminov RI

    更新日期:2017-09-26 00:00:00

  • Distinct Dysfunctional States of Circulating Innate-Like T Cells in Metabolic Disease.

    abstract::The immune system plays a significant role in controlling systemic metabolism. Innate-like T (ILT) cells in particular, such as mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells and γδ T cell receptor expressing cells, have been reported to promote metabolic homeostasis. However, the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00448

    authors: Li Y,Woods K,Parry-Strong A,Anderson RJ,Capistrano C,Gestin A,Painter GF,Hermans IF,Krebs J,Gasser O

    更新日期:2020-03-13 00:00:00

  • Fungal Infection in the Brain: What We Learned from Intravital Imaging.

    abstract::Approximately 1.2 billion people suffer from fungal diseases worldwide. Arguably, the most serious manifestation occurs when pathogenic fungi infect the brain, often causing fatal meningoencephalitis. For most fungi, infection occurs via the vascular route. The organism must first be arrested in the brain microvascula...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00292

    authors: Shi M,Mody CH

    更新日期:2016-08-02 00:00:00

  • O-Serotype Conversion in Salmonella Typhimurium Induces Protective Immune Responses against Invasive Non-Typhoidal Salmonella Infections.

    abstract::Salmonella infections remain a big problem worldwide, causing enteric fever by Salmonella Typhi (or Paratyphi) or self-limiting gastroenteritis by non-typhoidal Salmonella (NTS) in healthy individuals. NTS may become invasive and cause septicemia in elderly or immuno-compromised individuals, leading to high mortality ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01647

    authors: Li P,Liu Q,Luo H,Liang K,Yi J,Luo Y,Hu Y,Han Y,Kong Q

    更新日期:2017-12-04 00:00:00

  • Manipulation of Gut Microbiota Influences Immune Responses, Axon Preservation, and Motor Disability in a Model of Progressive Multiple Sclerosis.

    abstract::Gut microbiota dysbiosis has been implicated in MS and other immune diseases, although it remains unclear how manipulating the gut microbiota may affect the disease course. Using a well-established model of progressive MS triggered by intracranial infection with Theiler's murine encephalomyelitis virus (TMEV), we soug...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01374

    authors: Mestre L,Carrillo-Salinas FJ,Mecha M,Feliú A,Espejo C,Álvarez-Cermeño JC,Villar LM,Guaza C

    更新日期:2019-06-14 00:00:00

  • P2X7 Receptor Induces Tumor Necrosis Factor-α Converting Enzyme Activation and Release to Boost TNF-α Production.

    abstract::Tumor necrosis factor (TNF)-α is a major pro-inflammatory cytokine produced in response to toll-like receptor stimulation. TNF-α release is controlled by the activity of TNF-α converting enzyme (TACE) that cut membrane-bound TNF-α to shed its ectodomain as a soluble cytokine. The purinergic receptor P2X ligand-gated i...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00862

    authors: Barberà-Cremades M,Gómez AI,Baroja-Mazo A,Martínez-Alarcón L,Martínez CM,de Torre-Minguela C,Pelegrín P

    更新日期:2017-07-24 00:00:00

  • Thermodynamics of Peptide-MHC Class II Interactions: Not all Complexes are Created Equal.

    abstract::The adaptive immune response begins when CD4+ T cells recognize antigenic peptides bound to class II molecules of the Major Histocompatibility Complex (MHCII). The interaction between peptides and MHCII has been historically interpreted as a rigid docking event. However, this model has been challenged by the evidence ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2013.00308

    authors: Ferrante A

    更新日期:2013-10-01 00:00:00

  • MIF and CXCL12 in Cardiovascular Diseases: Functional Differences and Similarities.

    abstract::Coronary artery disease (CAD) as part of the cardiovascular diseases is a pathology caused by atherosclerosis, a chronic inflammatory disease of the vessel wall characterized by a massive invasion of lipids and inflammatory cells into the inner vessel layer (intima) leading to the formation of atherosclerotic lesions;...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00373

    authors: van der Vorst EP,Döring Y,Weber C

    更新日期:2015-07-21 00:00:00

  • Profiling of Canonical and Non-Traditional Cytokine Levels in Interferon-β-Treated Relapsing-Remitting-Multiple Sclerosis Patients.

    abstract:Background:Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing-remitting (RR) form, characterized by flare-ups followed by periods of recov...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01240

    authors: D'Angelo C,Reale M,Costantini E,Di Nicola M,Porfilio I,de Andrés C,Fernández-Paredes L,Sánchez-Ramón S,Pasquali L

    更新日期:2018-06-04 00:00:00

  • Adipocytes Directly Affect Coronary Artery Disease Pathogenesis via Induction of Adipokine and Cytokine Imbalances.

    abstract::This study aimed to investigate the adipokine and cytokine profiles of adipocytes from epicardial and subcutaneous adipose tissues in interconnection with the visceral adipose tissue area and the biochemical and clinical characteristics of patients with coronary artery disease. We assessed 84 patients with coronary ar...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02163

    authors: Gruzdeva O,Uchasova E,Dyleva Y,Borodkina D,Akbasheva O,Antonova L,Matveeva V,Belik E,Ivanov S,Sotnikov A,Kozyrin K,Brel N,Sinitsky M,Karetnikova V,Kokov A,Bychkova E,Pecherina T,Barbarash O

    更新日期:2019-09-19 00:00:00

  • Differential MicroRNA Expression Levels in Cutaneous Acute Graft-Versus-Host Disease.

    abstract::Allogeneic hematopoietic stem cell transplantation is a curative treatment for numerous hematological malignancies. However, acute graft-versus-host disease (aGvHD) is a major complication affecting 40-70% of all transplant patients, whereby the earliest and most frequent presentation is in the skin. MicroRNAs play a ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01485

    authors: Atarod S,Norden J,Bibby LA,Janin A,Ratajczak P,Lendrem C,Pearce KF,Wang XN,O'Reilly S,Van Laar JM,Collin M,Dickinson AM,Crossland RE

    更新日期:2018-07-10 00:00:00

  • Predictable Irreversible Switching Between Acute and Chronic Inflammation.

    abstract::Many a disease associates with inflammation. Upon binding of antigen-antibody complexes to immunoglobulin-like receptors, mast cells release tumor necrosis factor-α and proteases, causing fibroblasts to release endogenous antigens that may be cross reactive with exogenous antigens. We made a predictive dynamic map of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01596

    authors: Abudukelimu A,Barberis M,Redegeld FA,Sahin N,Westerhoff HV

    更新日期:2018-08-07 00:00:00

  • Functionally Convergent B Cell Receptor Sequences in Transgenic Rats Expressing a Human B Cell Repertoire in Response to Tetanus Toxoid and Measles Antigens.

    abstract::The identification and tracking of antigen-specific immunoglobulin (Ig) sequences within total Ig repertoires is central to high-throughput sequencing (HTS) studies of infections or vaccinations. In this context, public Ig sequences shared by different individuals exposed to the same antigen could be valuable markers ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01834

    authors: Bürckert JP,Dubois ARSX,Faison WJ,Farinelle S,Charpentier E,Sinner R,Wienecke-Baldacchino A,Muller CP

    更新日期:2017-12-22 00:00:00

  • miRNAs Predicted to Regulate Host Anti-viral Gene Pathways in IPNV-Challenged Atlantic Salmon Fry Are Affected by Viral Load, and Associated With the Major IPN Resistance QTL Genotypes in Late Infection.

    abstract::Infectious pancreatic necrosis virus (IPNV) infection has been a major problem in salmonid aquaculture. Marker-assisted selection of individuals with resistant genotype at the major IPN quantitative trait locus (IPN-QTL) has significantly reduced mortality in recent years. We have identified host miRNAs that respond t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.02113

    authors: Woldemariam NT,Agafonov O,Sindre H,Høyheim B,Houston RD,Robledo D,Bron JE,Andreassen R

    更新日期:2020-09-11 00:00:00

  • Combined p14ARF and Interferon-β Gene Transfer to the Human Melanoma Cell Line SK-MEL-147 Promotes Oncolysis and Immune Activation.

    abstract::Immune evasion is an important cancer hallmark and the understanding of its mechanisms has generated successful therapeutic approaches. Induction of immunogenic cell death (ICD) is expected to attract immune cell populations that promote innate and adaptive immune responses. Here, we present a critical advance for our...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.576658

    authors: Cerqueira OLD,Clavijo-Salomon MA,Cardoso EC,Citrangulo Tortelli Junior T,Mendonça SA,Barbuto JAM,Strauss BE

    更新日期:2020-10-22 00:00:00

  • Stimulation of monocytes by placental microparticles involves toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells.

    abstract::Human pregnancy is accompanied by a mild systemic inflammatory response, which includes the activation of monocytes circulating in maternal blood. This response is exaggerated in preeclampsia, a placental-dependent disorder specific to human pregnancies. We and others showed that placental syncytiotrophoblast membrane...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2014.00173

    authors: Joerger-Messerli MS,Hoesli IM,Rusterholz C,Lapaire O

    更新日期:2014-04-15 00:00:00