DOCSLIB.ORG

Syndrome of Serum Igm in Patients with Hyper-Igm Defective Self

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Syndrome of Serum Igm in Patients with Hyper-Igm Defective Self Defective Self-Reactive Antibody Repertoire of Serum IgM in Patients with Hyper-IgM Syndrome This information is current as Sébastien Lacroix-Desmazes, Igor Resnick, Dorothea Stahl, of September 25, 2021. Luc Mouthon, Teresa Espanol, Jacov Levy, Srini V. Kaveri, Luigi Notarangelo, Martha Eibl, Alain Fischer, Hans Ochs and Michel D. Kazatchkine J Immunol 1999; 162:5601-5608; ; http://www.jimmunol.org/content/162/9/5601 Downloaded from References This article cites 46 articles, 14 of which you can access for free at: http://www.jimmunol.org/content/162/9/5601.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Defective Self-Reactive Antibody Repertoire of Serum IgM in Patients with Hyper-IgM Syndrome1 Se´bastien Lacroix-Desmazes,* Igor Resnick,† Dorothea Stahl,* Luc Mouthon,* Teresa Espanol,‡ Jacov Levy,§ Srini V. Kaveri,* Luigi Notarangelo,¶ Martha Eibl,i Alain Fischer,** Hans Ochs,†† and Michel D. Kazatchkine2* We have analyzed the self-reactive repertoires of IgM and IgG Abs in the serum of 19 patients with hyper-IgM syndrome (HIM) by means of a quantitative immunoblotting technique that allows for a quantitative comparison of Ab repertoires in health and disease by multiparametric statistical analysis. Normal tissue extracts of liver, lung, stomach, and kidney were used as sources of self Ags. Extracts of Pseudomonas aeruginosa and Staphylococcus epidermidis were used as sources of nonself Ags. We demonstrate a significant bias in repertoires of reactivities of IgM of patients with HIM with self Ags. Ab repertoires of IgM toward nonself Downloaded from Ags did not differ, however, between patients and controls. No difference was found between IgM repertoires of untreated patients and those of patients receiving substitutive treatment with i.v. IgG. IgG in the serum of HIM patients lacked reactivity with self Ags, although it exhibited a pattern of reactivity with nonself Ags that was similar to that of IgG of healthy controls. The data demonstrate that functional CD40-CD40 ligand interactions are essential for the selection of natural self-reactive B cell repertoires. The Journal of Immunology, 1999, 162: 5601–5608. mmunodeficiency with hyper-IgM syndrome (HIM)3 is a rare thrombocytopenia or other autoimmune manifestations such as he- http://www.jimmunol.org/ disease characterized by normal or increased serum concen- molytic anemia and nephritis (1, 19). An increased incidence of I trations of IgM with decreased or absent IgG, IgA, and IgE autoantibodies, including anti-erythrocyte, anti-platelet, anti- (1, 2). HIM results from defective interactions between CD40 li- thyroid, anti-nuclear, anti-cardiolipin, and anti-smooth muscle gand (CD40L) on activated T cells and CD40 on B cells. The Abs, has been reported in patients with HIM (19–23). X-linked form of HIM (X-HIM) is characterized by defective Natural Abs of the IgM, IgG, and IgA isotypes that are reactive CD40L due to deletions/insertions, point mutations, or truncation with a broad range of self Ags are present in normal serum (24– in the CD40L-encoding gene (3–12). Several in vivo and in vitro 26). Ab repertoires of natural IgM and IgG toward self Ags are studies have documented that T cell-dependent isotype switch is highly homogeneous among healthy individuals and remain invari- by guest on September 25, 2021 strictly dependent on cognate interactions involving CD40 and ant with aging (27–30). Evidence obtained in mice suggests that CD40L and that impaired CD40-CD40L interactions inhibit the the selection of autoreactive B cells requires the presence of CD41 development of germinal centers and the generation of B memory T lymphocytes under conditions of both pathological and physio- cells (13–17). Patients with HIM lack germinal centers in second- logical autoimmunity (31–34). ary lymphoid organs (18). The patients suffer from recurrent upper In the present study, we analyzed the Ab repertoires of IgM and and lower respiratory tract infections and also present with an un- IgG in the serum of patients with HIM by means of a quantitative usual susceptibility to Pneumocystis carinii pneumonia and Cryp- immunoblotting technique that allows for multiparametric statisti- tosporidium infection, suggesting impaired T cell functions. HIM cal analysis of Ab reactivities with self and nonself Ags. We dem- patients often present with persistent neutropenia and may develop onstrate that Ab repertoires of IgM toward self Ags are skewed in patients with HIM, whereas repertoires directed toward bacterial Ags do not differ between patients and healthy controls. In addi- *Institut National de la Sante´et de la Recherche Me´dicale (INSERM), Unit 430 and Universite´Pierre et Marie Curie, Hoˆpital Broussais, Paris, France; †Research Institute tion, little reactivity with self Ags of IgG in the serum of patients of Hematology, Moscow, Russia; ‡Immunology Unit, Vall d’Hebron, Barcelona, with HIM was detected. Our observations demonstrate that the Spain; §Department of Pediatrics, Soroka Medical Center, Beer Sheva, Israel; ¶De- i lack of functional CD40-CD40L interactions and/or impaired T/B partment of Pediatrics, University of Brescia, Brescia, Italy; Institute of Immunology, University of Vienna, Vienna, Austria; **INSERM, Unit 429, Hoˆpital des Enfants- cell cooperation in HIM affect the selection processes of natural Malades, Paris, France; and ††Department of Pediatrics, University of Washington self-reactive B cell repertoires. Medical School, Seattle, WA 98195 Received for publication September 30, 1998. Accepted for publication February 12, 1999. Patients and Methods Patients The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance EDTA-plasma was obtained from 19 children (18 boys and 1 girl), between with 18 U.S.C. Section 1734 solely to indicate this fact. 3 and 14 years old, diagnosed with immunodeficiency with HIM. Twenty 1 This work was supported by Institut National de la Sante´et de la Recherche Me´di- healthy young adult male blood donors with a mean age of 34 6 5 years cale, France, and the Central Laboratory of the Swiss Red Cross (Bern, Switzerland). were used as normal controls. Previous studies from our laboratory had S.L.D. is a recipient of a grant from the Ministe`re de l’Education Nationale et de la demonstrated that self-reactive Ab repertoires in serum remain highly ho- Recherche, France. I.R. is a recipient of a grant from the European Union (PECO). mogeneous and invariant from early childhood to adulthood (29, 35). 2 Address correspondence and reprint requests to Dr. Michel D. Kazatchkine, IN- Sixteen of the male patients had X-HIM. Two male patients presented SERM U430, Hoˆpital Broussais, 96, rue Didot, 75014 Paris, France. with autosomal recessive HIM, and one female patient had secondary HIM 3 Abbreviations used in this paper: HIM, hyper-IgM syndrome; X-HIM, X-linked associated with congenital rubella. Activated PBMC totally lacked expres- HIM; CD40L, CD40 ligand; PCA, principal component analysis; LDA, linear dis- sion of the CD40L Ag in 11 X-HIM patients, whereas expression of the Ag criminant analysis; LDL, low density lipoprotein. was low in 3 patients (2 patients with X-HIM and 1 patient with autosomal Copyright © 1999 by The American Association of Immunologists 0022-1767/99/$02.00 5602 SELF-REACTIVE REPERTOIRES OF IgM IN THE HYPER-IgM SYNDROME recessive HIM) and unknown in the remaining 5 cases. All patients had corresponding to peaks of reactivity for concentrations of IgG between 50 suffered from severe and/or recurrent infections before diagnosis, including and 400 mg/ml and of IgM between 5 and 50 mg/ml. Saturation was upper respiratory tract infections (10 of 16), P. carinii pneumonia (2 of 16), achieved for concentrations of IgG and IgM above 400 and 50 mg/ml, and episodic or chronic infectious diarrhea (6 of 16 including Cryptospo- respectively. The reproducibility of the assay was 10% (variation coeffi- ridium infection in 3 cases). Hematological abnormalities included neutro- cient). The 95% confidence interval of the mean area under the curve penia in 11 patients and pure RBC aplasia in 2 patients due to parvovirus corresponding to each peak of immunoreactivity was 30% in the case of B19 infection, as previously reported (36). Nephritis was present in 1 pa- IgM and 25% in the case of IgG, as calculated by Student’s t test (27, 28). tient and arthritis in 2 patients (described in Ref. 1). Autosomal recessive HIM was diagnosed in 2 patients with low or normal expression of the Statistical analysis CD40L Ag, respectively, and suffering from upper respiratory tract infec- tions. One patient had secondary HIM associated with congenital rubella. Densitometric profiles of immunoblots were divided into sections corre- CD40L expression in this patient was normal, and the patient suffered sponding to individual peaks of immunoreactivity. Respective peak areas upper respiratory tract infections. Twelve of the 19 patients received sub- were calculated in the case of each tissue extract. To discriminate between stitutive therapy with i.v. Ig, in amounts ranging from 200 mg/kg/body individual repertoires, peak areas corresponding to sections obtained with weight every 5 wk to 600 mg/kg every 2 wk.
Load more

Recommended publications
  • Allergy, Asthma & Immunology Associates (Private Practice) 2808
    CURRICULUM VITAE Roger H. Kobayashi, M.D. Business Address: Allergy, Asthma & Immunology Associates (Private practice) 2808 South 80th Avenue, Suites 210 and 240, Omaha, NE 68124 (402) 391-1800 Fax (402) 391-1563 email: [email protected] Education: 6/1969 University of Nebraska, Lincoln, Nebraska, B.A. (Pre-Med/Economics) 9/69-6/73 University of Hawaii Medical School, Honolulu, Hawaii 6/72-5/75 University of Hawaii Graduate School, Honolulu, Hawaii, M.S. (Physiology) 9/74-4/75 UCSD School of Medicine & UCLA School of Medicine 7/73-5/75 University of Nebraska College of Medicine, Omaha, Nebraska, M.D. Academic Positions: 6/75-7/76 Pediatric Intern, University of Southern California School of Medicine, Los Angeles, California 7/76-7/77 Pediatric Resident, University of Southern California School of Medicine, Los Angeles, California 7/77-12/79 Fellowship, Pediatric Immunology & Allergy, UCLA School of Medicine, Los Angeles, California 1/80-6/84 Assistant Professor of Pediatrics and Medical Microbiology, University of Nebraska College of Medicine, Omaha, Nebraska 1/80-9/88 Director, Division of Allergy and Immunology, Department of Pediatrics, University of Nebraska 7/84-9/88 Associate Professor of Pediatrics, University of Nebraska College of Medicine 7/85-9/88 Associate Professor of Pathology and Medical Microbiology, University of Nebraska College of Medicine 9/88-1/90 Associate Professor of Pediatrics, UCLA School of Medicine, Los Angeles, CA 1/90-6/95 Assoc Clinical Prof of Pediatrics UCLA School of Medicine, Los Angeles, CA 6/95-present
    [Show full text]
  • Somatic Mosaicism in Wiskott–Aldrich Syndrome Suggests in Vivo Reversion by a DNA Slippage Mechanism
    Somatic mosaicism in Wiskott–Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism Taizo Wada*, Shepherd H. Schurman*, Makoto Otsu*, Elizabeth K. Garabedian*, Hans D. Ochs†, David L. Nelson‡, and Fabio Candotti*§ *Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; †Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; and ‡Immunophysiology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Communicated by Francis S. Collins, National Institutes of Health, Bethesda, MD, May 24, 2001 (received for review April 23, 2001) Somatic mosaicism caused by in vivo reversion of inherited muta- of whom showed a progressively mild clinical course because of tions has been described in several human genetic disorders. Back the selective growth advantage of the revertant lymphocytes. mutations resulting in restoration of wild-type sequences and The molecular mechanism leading to the reversion events has second-site mutations leading to compensatory changes have been remained unknown in most cases, except for the few cases where shown in mosaic individuals. In most cases, however, the precise crossing over or gene conversion has been shown in compound genetic mechanisms underlying the reversion events have re- heterozygous patients (11, 12). DNA polymerase slippage is the mained unclear, except for the few instances where crossing over most commonly invoked mechanism to explain triplet repeat or gene conversion have been demonstrated. Here, we report a expansion in human diseases (e.g., Huntington’s disease, fragile patient affected with Wiskott–Aldrich syndrome (WAS) caused by X syndrome, and Friedreich ataxia) (16).
    [Show full text]
  • Retrospective Diagnosis of X-Linked Hyper-Igm Syndrome in a Family With
    Letters to the Editor ical malignancies. One of the proband’s brothers (Patient Retrospective diagnosis of X-linked hyper-IgM III.4) was hospitalized 6-7 times a year with recurrent, syndrome in a family with multiple deaths of affected males severe bacterial infections of the gastrointestinal and res - piratory tracts until his death at age 10. Laboratory eval - uations between 1971 and 1977 demonstrated severe hypo-gammaglobulinemia with normal or elevated IgM All males in two generations of a Hungarian fam - levels (IgG, 0.85-2.95 g/L; IgA, 0.10-0.87 g/L; IgM, 1.37- ily died of interstitial pneumonia. History and 3.72 g/L). These data together with the family history records suggested X-linked hyper-IgM syndrome suggested X-HIG. 1-2 (X-HIGM). DNA sequencing of a female carrier We performed mutational analysis of the CD40L of the revealed a c. 654C →A transversion of the CD40L proband and her mother. The proband’s aunt (II.4) who gene that predicts premature termination of CD40L died at 70 years of age, and had no children, was not synthesis. This report points to the importance of available for genetic testing. Genomic DNA was isolated early carrier detection and genetic counseling in from whole blood samples. Exons 1 to 5 of the CD40L, families with X-linked primary immunodeficiency and the flanking intron regions were amplified by PCR. 3 diseases. We propose that the c.654C →A sequence The PCR products were sequenced with the BigDye variant may associate with severe X-HIGM pheno - Terminator Cycle sequencing kit (Applied Biosystems).
    [Show full text]
  • Agammaglobulinemia Hypogammaglobulinemia Hereditary Disease Immunoglobulins
    Pediat. Res. 2: 72-84 (1968) Agammaglobulinemia hypogammaglobulinemia hereditary disease immunoglobulins Hereditary Alterations in the Immune Response: Coexistence of 'Agammaglobulinemia', Acquired Hypogammaglobulinemia and Selective Immunoglobulin Deficiency in a Sibship REBECCA H. BUCKLEY[75] and J. B. SIDBURY, Jr. Departments of Pediatrics, Microbiology and Immunology, Division of Immunology, Duke University School of Medicine, Durham, North Carolina, USA Extract A longitudinal immunologic study was conducted in a family in which an entire sibship of three males was unduly susceptible to infection. The oldest boy's history of repeated severe infections be- ginning in infancy and his marked deficiencies of all three major immunoglobulins were compatible with a clinical diagnosis of congenital 'agammaglobulinemia' (table I, fig. 1). Recurrent severe in- fections in the second boy did not begin until late childhood, and his serum abnormality involved deficiencies of only two of the major immunoglobulin fractions, IgG and IgM (table I, fig. 1). This phenotype of selective immunoglobulin deficiency is previously unreported. Serum concentrations of the three immunoglobulins in the youngest boy (who also had a late onset of repeated infection) were normal or elevated when he was first studied, but a marked decline in levels of each of these fractions was observed over a four-year period (table I, fig. 1). We could find no previous reports describing apparent congenital and acquired immunologic deficiencies in a sibship. Repeated infections and demonstrated specific immunologic unresponsiveness preceded gross ab- normalities in the total and fractional gamma globulin levels in both of the younger boys (tables II-IV). When the total immunoglobulin level in the second boy was 735 mg/100 ml, he failed to respond with a normal rise in titer after immunization with 'A' and 'B' blood group substances, diphtheria, tetanus, or Types I and II poliovaccines.
    [Show full text]
  • Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency
    Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD, David A. Khan, MD, Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD, David I. Bernstein, MD, Joann Blessing-Moore, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Chief Editor: Francisco A. Bonilla, MD, PhD Co-Editor: David A. Khan, MD Members of the Joint Task Force on Practice Parameters: David I. Bernstein, MD, Joann Blessing-Moore, MD, David Khan, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Primary Immunodeficiency Workgroup: Chairman: Francisco A. Bonilla, MD, PhD Members: Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD GlaxoSmithKline, Merck, and Aerocrine; has received payment for lectures from Genentech/ These parameters were developed by the Joint Task Force on Practice Parameters, representing Novartis, GlaxoSmithKline, and Merck; and has received research support from Genentech/ the American Academy of Allergy, Asthma & Immunology; the American College of Novartis and Merck.
    [Show full text]
  • X Inactivation and Immunocompetence in Female Carriers of the X-Linked Hyper-Igm Syndrome
    X inactivation and immunocompetence in female carriers of the X-linked hyper-IgM syndrome. T J Kipps J Clin Invest. 1994;94(2):469-469. https://doi.org/10.1172/JCI117355. Editorial Find the latest version: https://jci.me/117355/pdf X Inactivation and Immunocompetence in Female Carriers of the X-linked Hyper-lgM Syndrome Editorial Immunocompetence requires cognate cell-cell communication severe combined immune deficiency, in which carriers predomi- that is mediated through cell surface ligand-receptor interac- nately generate mature lymphocytes that express the normal tions (1). An important player in such interactions is CD40, a allele. type I membrane glycoprotein that is expressed by a variety of Cases of extreme Lyonization can result in phenotype ex- cells, including B cells, monocytes, dendritic cells, and thymic pression of an X-linked disease in the female carrier, as has epithelial cells. Crosslinking this surface molecule can induce been noted in cases of Wiskott-Aldrich syndrome, hemophilia maturation, activation, and/or proliferation of CD40-bearing A, or Duchenne muscular dystrophy. However, with regard to cells. This is mediated by the CD40-ligand (otherwise called the relative number of T cells that can express a functional gp39 or TRAP), a type II membrane glycoprotein that is ex- CD40-ligand, it seems that a little can go a long way. This may pressed on the surface of T cells 6-8 h after their immune reflect the presence of signaling pathways other than that of the activation (2). CD40-CD40-ligand, that, once primed by a relatively small The importance of the CD40-CD40-ligand interaction is number of CD40-ligand-expressing T cells, can perpetuate the underscored by the X-linked hyper-IgM syndrome.
    [Show full text]
  • CDG and Immune Response: from Bedside to Bench and Back Authors
    CDG and immune response: From bedside to bench and back 1,2,3 1,2,3,* 2,3 1,2 Authors: Carlota Pascoal , Rita Francisco , Tiago Ferro , Vanessa dos Reis Ferreira , Jaak Jaeken2,4, Paula A. Videira1,2,3 *The authors equally contributed to this work. 1 Portuguese Association for CDG, Lisboa, Portugal 2 CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN), Caparica, Portugal 3 UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal 4 Center for Metabolic Diseases, UZ and KU Leuven, Leuven, Belgium Word count: 7478 Number of figures: 2 Number of tables: 3 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jimd.12126 This article is protected by copyright. All rights reserved. Abstract Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein-attached glycans that mediate cell-cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are Congenital Disorders of Glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterised by an increased propensity to – often life-threatening – infection.
    [Show full text]
  • Blueprint Genetics Severe Combined Immunodeficiency Panel
    Severe Combined Immunodeficiency Panel Test code: IM0101 Is a 80 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of combined immunodeficiencies. The genes on this panel are included in the Primary Immunodeficiency Panel. About Severe Combined Immunodeficiency Severe combined immunedeficiencies (SCIDs) are a group of primary immunodeficiencies characterized by specific mutations in genes of T and B-lymphocyte systems and leading to little or no immune response. Different subtypes of SCIDs are characterized and subdivided by the presence of circulating T and B cells. T cells are absent or markedly decreased in the most types, but levels of B cells vary. In addition, both of these disease subgroups (T-B+ and T-B-) can occur with or without NK cells. Patients with SCID are susceptible to recurrent infections that can be fatal. The worldwide prevalence of SCID is estimated to be at least 1:100,000 births, while some genetically more homogenous populations may show markedly increased numbers. Mutations in IL2RG are the most common reason for SCIDs, explaining approximately 50% of all cases and close to 100% of X-linked cases. Availability 4 weeks Gene Set Description Genes in the Severe Combined Immunodeficiency Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ADA Severe combined immunodeficiency due to adenosine deaminase AR 49 93 deficiency AK2 Reticular dysgenesis AR 14 17 ATM Breast cancer, Ataxia-Telangiectasia AD/AR 1047 1109 BCL11B Immunodeficiency
    [Show full text]
  • Selective Igm Deficiency—An Underestimated Primary Immunodeficiency
    UC Irvine UC Irvine Previously Published Works Title Selective IgM Deficiency-An Underestimated Primary Immunodeficiency. Permalink https://escholarship.org/uc/item/6wg240n5 Journal Frontiers in immunology, 8(SEP) ISSN 1664-3224 Authors Gupta, Sudhir Gupta, Ankmalika Publication Date 2017 DOI 10.3389/fimmu.2017.01056 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California REVIEW published: 05 September 2017 doi: 10.3389/fimmu.2017.01056 Selective IgM Deficiency—An Underestimated Primary Immunodeficiency Sudhir Gupta* and Ankmalika Gupta† Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, CA, United States Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD. A number Edited by: of B cell subset abnormalities have been reported and impaired specific antibodies Guzide Aksu, to Streptococcus pneumoniae responses are observed in more than 45% of cases. Ege University, Turkey Innate immunity, T cells, T cell subsets, and T cell functions are essentially normal. Reviewed by: Amos Etzioni, The pathogenesis of SIGMD remains unclear. Mice selectively deficient in secreted IgM University of Haifa, Israel are also unable to control infections from bacterial, viral, and fungal pathogens, and Isabelle Meyts, develop autoimmunity.
    [Show full text]
  • Prevention of Infections During Primary Immunodeficiency
    Clinical Infectious Diseases Advance Access published September 28, 2014 INVITED ARTICLE IMMUNOCOMPROMISED HOSTS David R. Snydman, Section Editor Prevention of Infections During Primary Immunodeficiency Claire Aguilar,1,2,3 Marion Malphettes,1,4 Jean Donadieu,1,5 Olivia Chandesris,1,3,6 Hélène Coignard-Biehler,1,2,3 Emilie Catherinot,1,7 Isabelle Pellier,1,8 Jean-Louis Stephan,1,9 Vincent Le Moing,1,10 Vincent Barlogis,1,11 Felipe Suarez,1,3,6 Stéphane Gérart,3 Fanny Lanternier,1,2,3 Arnaud Jaccard,1,12 Paul-Henri Consigny,2 Florence Moulin,13 Odile Launay,14 Marc Lecuit,1,2,3 Olivier Hermine,1,3,6 Eric Oksenhendler,1,4 Capucine Picard,1,3,15,16,a Stéphane Blanche,1,3,16,a Alain Fischer,1,3,16,17,a Nizar Mahlaoui,1,3,16 and Olivier Lortholary1,2,3 1Centre de Référence des Déficits Immunitaires Héréditaires, and 2Centre d’Infectiologie Necker Pasteur, Hôpital Necker–Enfants Malades, Assistance publique–Hôpitaux de Paris (AP-HP), 3Sorbonne Paris Cité, Université Paris Descartes, Institut-Hospitalo-Universitaire (IHU) Imagine, 4Département ’ 5 ’ 6 d Immunologie, Hôpital Saint-Louis, Service d Hémato-Oncologie Pédiatrique, Registre des Neutropénies Congénitales, Hôpital Trousseau, Service Downloaded from d’Hématologie Adulte, IHU Imagine, Hôpital Necker–Enfants Malades, AP-HP, Paris, 7Service de Pneumologie, Hôpital Foch, Suresnes, 8Unité d’Immuno- Hématologie-Oncologie Pédiatrique, Centre Hospitalier Universitaire (CHU) d’Angers, 9Unité d’Immuno-Hématologie-Oncologie Pédiatrique, CHU de Saint- Etienne, 10Service des Maladies Infectieuses et
    [Show full text]
  • Common Variable Immunodeficiency (CVID)
    UNIVERSIDADE DE LISBOA FACULDADE DE MEDICINA DE LISBOA AUTOIMUNIDADE E CÉLULAS REGULADORAS + HIGH T CD4 CD25 NA IMUNODEFICIÊNCIA COMUM VARIÁVEL Susana Clara Barão Lopes da Silva dos Anjos MESTRADO EM IMUNOLOGIA MÉDICA 2007 UNIVERSIDADE DE LISBOA FACULDADE DE MEDICINA DE LISBOA AUTOIMUNIDADE E CÉLULAS REGULADORAS + HIGH T CD4 CD25 NA IMUNODEFICIÊNCIA COMUM VARIÁVEL Susana Clara Barão Lopes da Silva dos Anjos Mestrado em Imunologia Médica Dissertação orientada pelo Professor Doutor Antero G. Palma-Carlos Todas as afirmações efectuadas no presente documento são da exclusiva responsabilidade do seu autor, não cabendo qualquer responsabilidade à Faculdade de Medicina de Lisboa pelos conteúdos nele apresentados 2007 A impressão esta dissertação foi aprovada em Comissão Coordenadora do Conselho Científico da Faculdade de Medicina de Lisboa, em reunião de 8 de Maio de 2007. Good research brings you more questions than answers. Sir John Vane, Nobel Prize 1982 RESUMO Introdução: Vários mecanismos têm sido sugeridos para explicar a elevada prevalência de doenças autoimunes (DAIs) na Imunodeficiência Comum Variável (ICV). Procurámos avaliar a prevalência de DAIs numa população com IDCV, caracterizar estes doentes e verificar se um defeito quantitativo na população T CD4+CD25high poderia estar associado à maior prevalência de autoimunidade na ICV. Métodos: Foram incluídos 47 doentes com ICV sob terapêutica substitutiva com imunoglobulina endovenosa (IGEV). Através de revisão dos processos clínicos e entrevista individual foram recolhidos dados clínicos e laboratoriais relativamente às manifestações de apresentação e evolução clínica, incluindo DAIs e níveis séricos de imunoglobulinas no diagnóstico de ICV. Em estudo transversal, foi quantificada IgG sérica e populações T, B e NK e células T CD4CD25 por citometria de fluxo em sangue total.
    [Show full text]
  • X-Linked Hyper-Igm Syndrome with Bronchiectasis
    Published online: 2020-04-19 X‑linked Hyper‑IgM Syndrome with Bronchiectasis Devki Nandan, Vimal Kumar Nag, Nitin Trivedi, Sarman Singh1 Report Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Dr. Ram Manohar Lohia Hospital, 1Department of Clinical Microbiology, All India Institute of Medical Sciences, New Delhi, India Address for correspondence: Dr. Devki Nandan, E-mail: [email protected] Case ABSTRACT The X-linked hyper-immunoglobulin M syndrome (HIGM-1) is a rare genetic disorder characterized by elevated serum IgM levels and low to undetectable levels of serum IgG, IgA and IgE. These patients characteristically present with recurrent sinopulmonary infections and recurrent diarrhea. They also have high susceptibility for Pneumocystis jiroveci (PJ) pneumonia. Herein, we report a case of HGM-1 in a 5-year-old boy who presented with bronchiectasis and, possibly, PJ pneumonia. The diagnosis was established on the basis of clinical features, immune profile, whole blood flow cytometry and history of two male sibling’s death due to recurrent pneumonia and diarrhea. Key words: Bronchiectasis, children, Pneumocystis jiroveci, X-linked hyper-IgM syndrome INTRODUCTION CASE REPORT yper‑immunoglobulin M syndrome (HIGM) A 5‑year‑old boy, born of consanguineous (4th degree) H is a rare heterogeneous group of marriage, presented with complaints of productive disorders, 70% of which are due to CD40‑ligand cough and right ear discharge since 1 year, fever and deficiency.[1] These patients are susceptible to respiratory distress for 25 days and oral thrush since recurrent sinopulmonary infections and opportunistic 20 days. infections, especially Pneumocystis jiroveci pneumonia. Bronchiectasis is characterized by abnormal He had a history of five admissions in various hospitals dilated thick‑walled bronchi that are inflamed and for pneumonia since the age of 1 year.
    [Show full text]