Roger Colobran

Roger Colobran
University Hospital Vall d'Hebron · Immunology Division

34.6
 · 
PhD

About

79
Publications
6,664
Reads
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683
Citations
Introduction
Head of Immunogenetics Area in Hospital Vall d'Hebron (Barcelona). Immunology Division. Clinical and Molecular Genetics Area. Expertise in Immunology and Genetics. Interests: Autoimmunity, Central Tolerance, Thymus, Immunogenetics, Molecular Diagnòstic of Primary Immunodeficiencies, Mutations, SNPs, CNVs, Genomic Variation.
Research Experience
March 2016 - present
University Hospital Vall d'Hebron
Position
  • Head of Immunogenetics Area / Researcher
September 2013 - present
Autonomous University of Barcelona
Position
  • Professor (Associate)
July 2011 - February 2016
VHIR Vall d’Hebron Research Institute
Position
  • Post-doctoral Researcher

Publications

Publications (79)
Article
Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumon...
Article
Full-text available
Autoinflammatory 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...
Article
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X-linked agammaglobulinemia (XLA) is a clinically and genetically well-defined immunodeficiency and the most common form of agammaglobulinemia. It is characterized by susceptibility to recurrent bacterial infections, profound hypogammaglobulinemia, and few or no circulating B cells. XLA is caused by mutations in the BTK gene, which encodes Bruton's...
Article
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Background: Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders. The lack of comprehensive disease-specific mutation databases may hinder or delay classification of the genetic variants found in samples from these patients. This is especially true for familial hemophagocytic lymphohistiocytosis (FHL), a life-threatening PID cla...
Article
The presence of mutations in PRF1, UNC13D, STX11 and STXBP2 genes in homozygosis or compound heterozygosis results in immune deregulation. Most such cases lead to clinical manifestations of haemophagocytic lymphohistiocytosis (HLH). In the present study, we analyzed degranulation and cytotoxicity in a pediatric patient with a late presentation of H...
Article
In addition to their detection in typical X‐linked severe combined immunodeficiency, hypomorphic mutations in the IL‐2 receptor common gamma chain gene (IL2RG) have been described in patients with atypical clinical and immunological phenotypes. In this leaky clinical phenotype, the diagnosis is often delayed, limiting prompt therapy in these patien...
Article
Full-text available
Background: The current scenario of newborn screening is changing as DNA studies are being included in the programs of several countries. Severe combined immunodeficiency (SCID) disorders can be detected using quantitative PCR assays to measure T-cell receptor excision circles (TRECs), a byproduct of correct T-cell development. However, in additio...
Article
Full-text available
Primary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of genetic defects in PID patients in daily clinical prac...
Article
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Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn scre...
Article
Autoimmune thyroid diseases (AITDs), i.e., Graves' disease (GD) and Hashimoto thyroiditis (HT), are the most prevalent organ-specific autoimmune diseases, but their pathogenesis is still incompletely understood. The PD-1/PD-L1 pathway is an important mechanism of peripheral tolerance that has not been investigated in AITDs. Here, we report the anal...
Article
Full-text available
Graves' disease (GD) involves the presence of agonistic auto-antibodies against the thyrotropin receptor (TSHR), which are responsible for the clinical symptoms. While failure of TSHR tolerance is central to GD pathogenesis, the process leading to this failure remains poorly understood. Two mechanisms intimately linked to tolerance have been propos...
Article
Full-text available
Mendelian diseases have shown to be an efficient model for connecting genotypes to phenotypes and for elucidating the function of genes. Whole‐exome sequencing (WES) accelerated the study of rare Mendelian diseases in families, allowing for directly pinpointing rare causal mutations in genic regions without the need for linkage analysis. However, t...
Article
In the last 3 years, the association of thyrotropin receptor gene (TSHR) variations to Graves’ disease (GD) has been confirmed. It is now well established that a 30 Kb region of intron 1 of the TSHR gene is linked to GD predisposition. Elucidating the mechanism(s) by which these polymorphisms confer susceptibility is difficult but would constitute...
Article
Full-text available
Background For the accurate diagnosis of immunodeficiencies is crucial to compare patients’ immunology laboratory values with age‐sex matched controls, yet there is a paucity of normal values for most populations. Objectives To define appropriate reference values of extended lymphocyte subpopulations and T‐cell receptor excision circle (TRECs) lev...
Article
Full-text available
LRBA deficiency was first described in 2012 as an autosomal recessive disorder caused by biallelic mutations in the LRBA gene (OMIM #614700). It was initially characterized as producing early-onset hypogammaglobulinemia, autoimmune manifestations, susceptibility to inflammatory bowel disease, and recurrent infection. However, further reports expand...
Article
Background: Post-zygotic de novo mutations lead to the phenomenon of gene mosaicism. The three main types are called somatic, gonadal and gonosomal mosaicism, which differ on the body distribution of post-zygotic mutations. Mosaicism has been occasionally reported in primary immunodeficiency diseases (PID) since early 90s, but its real involvement...
Article
Monoallelic loss-of-function mutations in NFKB1 were recently recognized as the most common monogenic cause of common variable immunodeficiency (CVID). The prototypic clinical phenotype of NFKB1-deficient patients includes common CVID features, such as hypogammaglobulinaemia and sinopulmonary infections, plus other highly variable individual manife...
Article
The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and...
Article
Full-text available
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency characterized by recurrent infections, hypogammaglobulinemia and poor response to vaccines. Its diagnosis is made based on clinical and immunological criteria, after exclusion of other diseases that can cause similar phenotypes. Currently, less than 20...
Article
There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 gene...
Article
Full-text available
The complement system is an important effector arm of innate immunity and plays a crucial role in the defense against common pathogens. But effective defense and maintenance of homeostasis requires a careful balance between complement activation and regulation. Factor I (FI) is one of the most important regulators of the complement system. Complete...
Article
Background: Low C3 either secondary to comsumption/low production, to C3 nephritic factor and antifactor H auto-antibodies or, more rarely, due to deficiencies in the regulatory proteins factor H, factor I or Factor B or C3 itself, predisposes to infection by encapsulated microorganisms, and is associated to autoimmunity. In previous studies, we ha...
Article
Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in...
Conference Paper
Introduction: X-linked Severe Combined Immunodeficiency (X-SCID) is the most frequent form of SCID, caused by mutations in the gene encoding the IL-2-receptor γ-chain (IL2RG). This immunodeficiency is characterized by severe lymphopenia and recurring persistent infections in the first months of life. The common γ-chain works as signal-transducing s...
Conference Paper
Full-text available
Introduction. A new primary antibody deficiency caused by hyperactivation of the PI3K signaling pathway was described in 2014, consisting of two closely related entities: one is caused by gain-of-function mutations in PIK3CD encoding for the p110δ subunit resulting in “Activated PI3Kδ Syndrome 1” (APDS1) and the other is caused by an activating het...
Article
Complement factor I (CFI) deficiency is typically associated to recurrent infections with encapsulated microorganisms and, less commonly, to autoimmunity. We report a 53-years old male who, in a routine control for non-alcoholic fatty liver disease, presented a flat beta-2 fraction at the capillary protein electropherogram. Patient's clinical recor...
Article
The complement system plays a central role in defense to encapsulated bacteria through opsonization and membrane attack complex (MAC) dependent lysis. The three activation pathways (classical, lectin, and alternative) converge in the cleavage of C5, which initiates MAC formation and target lysis. C5 deficiency is associated to recurrent infections...
Article
The transmembrane glycoprotein CD26 or dipeptidyl peptidase IV (DPPIV) is a multifunctional protein. In immune system, CD26 plays a role in T-cell function and is also involved in thymic maturation and emigration patterns. In preclinical studies, treatment with DPPIV inhibitors reduces insulitis and delays or even reverses the new -onset of type 1...
Article
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CD26 is a T cell activation marker consisting in a type II transmembrane glycoprotein with dipeptidyl peptidase IV (DPPIV) activity in its extracellular domain. It has been described that DPPIV inhibition delays the onset of type 1 diabetes and reverses the disease in non-obese diabetic (NOD) mice. The aim of the present study was to assess the eff...
Article
Full-text available
As most autoimmune diseases, inherited predisposition to Graves' disease (GD) is polygenic with the main contributory genes being located in the HLA region. Also, as in other autoimmune diseases, family linkage, candidate gene association, and GWAS studies have identified an expanding number of predisposing genes (CTLA4, CD40, PTPN22...) and 2 of t...
Poster
Familial hemophagocytic lymphohistiocytosis (FHL)is a life-treating autosomal recessive disease caused by an impaired cytotoxicity. Recently, the synergistic effect of heterozygous and dominant negative mutations in cytotoxic pathway has been described as new inherited forms of this condition.
Poster
Hemophagocytic lymphohistiocytosis and subcutaneous panniculitis T-cell lymphoma associated to a heterozygous mutation in STXBP2
Article
Full-text available
Graves' disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients. We previously demonstrated that TSHR, the target of this autoimmune response, is also a key susceptibility gene for GD,...
Article
Full-text available
Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the...
Article
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal-dominant and life-threatening disorder caused by mutations in SERPING1 gene. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. Here we report the case of a patient with HAE-C1IN...
Article
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal-dominant disease caused by mutations in SERPING1 gene. The main clinical feature of C1INH deficiency is the spontaneous edema of the subcutaneous and submucosal layers. More than 280 different mutations scattering the entire SERPING1 gene have been reported. We ide...
Article
DNA methylation, which most commonly occurs at the C5 position of cytosines within CpG dinucleotides, is one of several epigenetic mechanisms that cells use to control gene expression. The importance of DNA methylation in a variety of biological processes (i.e., embryonic development, cellular proliferation and differentiation, chromosome stability...
Article
Full-text available
Down syndrome (DS), a chromosomal condition caused by the trisomy of chromosome 21, is associated with various immunological impairments, including a high incidence of autoimmune diseases (e.g., hypothyroidism, type 1 diabetes) and anatomical changes in the thymus. The autoimmune regulator (AIRE) is a transcription factor whose gene maps in 21q22.3...
Article
Full-text available
Graves’ disease (GD) is the paradigm of an anti-receptor autoimmune disease with agonistic auto-antibodies against the thyrotropin receptor (TSHR) being the underlying pathogenic mechanism. TSHR belongs to the category of tissue-restricted antigens (TRAs), which are expressed by medullary thymic epithelial cells (mTECs) and thereby induce central T...
Article
Full-text available
Graves' disease (GD) is the paradigm of an anti-receptor autoimmune disease, with agonistic auto-antibodies against the thyrotropin receptor (TSHR-thyroid-stimulating hormone receptor) being the underlying pathogenic effector mechanism. The TSHR belongs to the category of tissue-restricted antigens, which are promiscuously expressed in the thymus a...
Article
Full-text available
Psoriasis is a common inflammatory skin disease with key immunological and genetic components. Recruitment of leukocytes into the skin is a central step in its pathogenesis, mediated by cytokines. Among the cytokines expressed in psoriatic lesions, C-C chemokine ligand 4 (CCL4) and C-C chemokine ligand 4-like (CCL4L) chemokines appear to be pivotal...
Article
Graves' disease (GD) is a chronic autoimmune process in the thyroid gland and involves IFN and IFN driven immune activation. Assuming the thyroid gland is the main site stimulating the autoimmune response, we investigated the role of IFNs and other factors in the chronic evolution of GD by comparing the transcriptomic profiles of thyroid glands fro...
Article
Psoriasis is a common inflammatory skin disease with key immunological and genetic components. Recruitment of leukocytes into the skin is a central step in its pathogenesis, mediated by cytokines. Among the cytokines expressed in psoriatic lesions, C-C chemokine ligand 4 (CCL4) and C-C chemokine ligand 4-like (CCL4L) chemokines appear to be pivotal...
Article
Genome copy number changes (copy number variations: CNVs) include inherited, de novo and somatically acquired deviations from a diploid state within a particular chromosomal segment. CNVs are frequent in higher eukaryotes and associated with a substantial portion of inherited and acquired risk for various human diseases. CNVs are distributed widely...
Chapter
There is a structural and a functional classification of chemokines. The former includes four groups: CXC, CC, C and CX3C chemokines. There is a redundancy and binding promiscuity between chemokine receptors and their ligands. Recently, a functional classification distinguishing between inflammatory and homeostatic chemokines has been introduced. H...
Article
Full-text available
Lung transplantation (LT) has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful LT is rejection of the transplanted organ where chemokines are pivotal mediators. Here, we test the relationship between copy number variation (CNV) in the CCL4L chemokine gene and rejection risk in LT...
Article
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The recent description of a large amount of copy number variation (CNV) in the human genome has extended the concept of genome diversity. In this study we integrate the analysis of CNV and single nucleotide polymorphisms (SNPs) in the human CCL4L chemokine gene. CCL4L is a nonallelic copy of CCL4/MIP-1beta chemokine and displays a CNV that also inc...
Article
In this second review on chemokines, we focus on the polymorphisms and alternative splicings and on their consequences in disease. Because chemokines are key mediators in the pathogenesis of inflammatory, autoimmune, vascular and neoplastic disorders, a large number of studies attempting to relate particular polymorphisms of chemokines to given dis...
Article
Chemokines are a superfamily of small structurally related cytokines that have evolved to form a complex network of proteins that typically regulate leucocyte traffic but also carry very diverse sets of immune and non-immune functions. Two general features of cytokines, redundancy and promiscuity, are particularly prominent in chemokines. In part,...
Article
Full-text available
Is a commercial product always reliable? Using CCL4 and CCL4L1 chemokines as a model, this work shows important changes in the sequences of a commercial product. The detected confusions in CCL4 and CCL4L1 can entail important consequences, particularly in experiments aimed at defining functional activities or cellular effects of these molecules. We...
Article
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Human CCL4/macrophage inflammatory protein (MIP)-1beta and CCL3/MIP-1alpha are two highly related molecules that belong to a cluster of inflammatory CC chemokines located in chromosome 17. CCL4 and CCL3 were formed by duplication of a common ancestral gene, generating the SCYA4 and SCYA3 genes which, in turn, present a variable number of additional...
Article
Polymerase chain reaction (PCR)-based human leukocyte antigen (HLA) typing methods currently used in most histocompatibility laboratories, such as PCR-sequence-specific primers (PCR-SSP) and PCR-sequence-specific oligonucleotide probes (PCR-SSO), are time-consuming and are at risk of contamination during the post-PCR process. The aim of this study...