Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 5/2017

Open Access 01-07-2017 | Original Article

Advances in the Care of Primary Immunodeficiencies (PIDs): from Birth to Adulthood

Authors: Nizar Mahlaoui, Klaus Warnatz, Alison Jones, Sarita Workman, Andrew Cant

Published in: Journal of Clinical Immunology | Issue 5/2017

Login to get access

Abstract

Primary immunodeficiencies (PIDs) are a widely heterogeneous group of inherited defects of the immune system consisting of many clinical phenotypes with at least 300 underlying genetic deficits currently known. Patients with PIDs can present with, or develop during the course of their life, a susceptibility to recurrent and chronic infection along with autoimmune, allergic, inflammatory, and/or proliferative disorders, all potentially leading to end-organ damage. In recent years, a combination of basic and clinical research has greatly improved understanding of the underlying immunological and genetic defects in PIDs, leading to improved diagnosis, classification, and treatment approaches. In this review, we consider some of the key understandings that should direct diagnostic and treatment approaches in PID and offer insights into current and emerging management approaches and the lifelong care of patients from childhood through to adulthood.
Literature
1.
Picard C, Al-Herz W, Bousfiha A, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol 2015.
2.
Parvaneh N, Casanova JL, Notarangelo LD, Conley ME. Primary immunodeficiencies: a rapidly evolving story. J Allergy Clin Immunol. 2013;131:314–23.CrossRefPubMed
3.
Fischer A, Hacein-Bey Abina S, Touzot F, Cavazzana M. Gene therapy for primary immunodeficiencies. Clin Genet. 2015;88:507–15.CrossRefPubMed
4.
5.
Picard C, Fischer A. Contribution of high-throughput DNA sequencing to the study of primary immunodeficiencies. Eur J Immunol. 2014;44:2854–61.CrossRefPubMed
6.
Lilic D. New perspectives on the immunology of chronic mucocutaneous candidiasis. Curr Opin Infect Dis. 2002;15:143–7.CrossRefPubMed
7.
Lilic D, Cant AJ, Abinun M, Calvert JE, Spickett GP. Chronic mucocutaneous candidiasis. I. Altered antigen-stimulated IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) production. Clin Exp Immunol. 1996;105:205–12.CrossRefPubMedPubMedCentral
8.
Lilic D, Gravenor I, Robson N, et al. Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis. Infect Immun. 2003;71:5690–9.CrossRefPubMedPubMedCentral
9.
van de Veerdonk FL, Plantinga TS, Hoischen A, et al. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med. 2011;365:54–61.CrossRefPubMed
10.
Brown L, Xu-Bayford J, Allwood Z, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117:3243–6.CrossRefPubMed
11.
Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312:729–38.CrossRefPubMedPubMedCentral
12.
Gaspar HB, Hammarstrom L, Mahlaoui N, Borte M, Borte S. The case for mandatory newborn screening for severe combined immunodeficiency (SCID). J Clin Immunol. 2014;34:393–7.CrossRefPubMed
13.
14.
Cunningham-Rundles C, Warnatz K. Chapter 14. Stiehm’s Immune Deficiencies Ed: Sullivan/Stiehm. 2014;
15.
Bonilla FA, Barlan I, Chapel H, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4:38–59.CrossRefPubMed
16.
Gathmann B, Mahlaoui N, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134:116–26.CrossRefPubMed
17.
Mouillot G, Carmagnat M, Gerard L, et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010;30:746–55.CrossRefPubMed
18.
Chapel H, Lucas M, Patel S, et al. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J Allergy Clin Immunol. 2012;130:1197–8. e9 CrossRefPubMed
19.
Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119:1650–7.CrossRefPubMedPubMedCentral
20.
Oksenhendler E, Gerard L, Fieschi C, et al. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis. 2008;46:1547–54.CrossRefPubMed
21.
Malphettes M, Gerard L, Carmagnat M, et al. Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin Infect Dis. 2009;49:1329–38.CrossRefPubMed
22.
van de Ven AA, Warnatz K. The autoimmune conundrum in common variable immunodeficiency disorders. Curr Opin Allergy Clin Immunol. 2015;15:514–24.CrossRefPubMed
23.
24.
Lopez-Herrera G, Tampella G, Pan-Hammarstrom Q, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90:986–1001.CrossRefPubMedPubMedCentral
25.
Kuehn HS, Niemela JE, Rangel-Santos A, et al. Loss-of-function of the protein kinase C delta (PKCdelta) causes a B-cell lymphoproliferative syndrome in humans. Blood. 2013;121:3117–25.CrossRefPubMedPubMedCentral
26.
Angulo I, Vadas O, Garcon F, et al. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342:866–71.CrossRefPubMedPubMedCentral
27.
Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15:88–97.CrossRefPubMed
28.
29.
Flanagan SE, Haapaniemi E, Russell MA, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet. 2014;46:812–4.CrossRefPubMedPubMedCentral
30.
Fliegauf M, Bryant VL, Frede N, et al. Haploinsufficiency of the NF-kappaB1 subunit p50 in common variable immunodeficiency. Am J Hum Genet. 2015;97:389–403.CrossRefPubMedPubMedCentral
31.
Keller A, Backes C, Haas J, et al. Validating Alzheimer's disease micro RNAs using next-generation sequencing. Alzheimers Dement. 2016;12:565–76.CrossRefPubMed
32.
Gamez-Diaz L, August D, Stepensky P, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137:223–30.CrossRefPubMed
33.
34.
35.
Ghosh S, Bienemann K, Boztug K, Borkhardt A. Interleukin-2-inducible T-cell kinase (ITK) deficiency—clinical and molecular aspects. J Clin Immunol. 2014;34:892–9.CrossRefPubMedPubMedCentral
36.
Belot A, Kasher PR, Trotter EW, et al. Protein kinase C delta deficiency causes Mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. Arthritis Rheum. 2013;65:2161–71.CrossRefPubMedPubMedCentral
37.
38.
Fevang B, Yndestad A, Sandberg WJ, et al. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin Exp Immunol. 2007;147:521–5.CrossRefPubMedPubMedCentral
39.
40.
Shulzhenko N, Morgun A, Hsiao W, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med. 2011;17:1585–93.CrossRefPubMedPubMedCentral
41.
Perreau M, Vigano S, Bellanger F, et al. Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders. J Exp Med. 2014;211:2033–45.CrossRefPubMedPubMedCentral
42.
Ebadi M, Aghamohammadi A, Rezaei N. Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics. Expert Rev Clin Immunol. 2015;11:117–39.CrossRefPubMed
43.
44.
Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol. 2010;137:21–30.CrossRefPubMed
45.
Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125:1354–60. e4 CrossRefPubMed
46.
Milner JD, Vogel TP, Forbes L, et al. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood. 2015;125:591–9.CrossRefPubMedPubMedCentral
47.
Liu L, Okada S, Kong XF, et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med. 2011;208:1635–48.CrossRefPubMedPubMedCentral
48.
Gennery AR, Slatter MA, Grandin L, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126:602–10. e1-11 CrossRefPubMed
49.
Gungor T, Teira P, Slatter M, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383:436–48.CrossRefPubMed
50.
Wehr C, Gennery AR, Lindemans C, et al. Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency. J Allergy Clin Immunol. 2015;135:988–97. e6 CrossRefPubMed
51.
Bertaina A, Merli P, Rutella S, et al. HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B cells in children with nonmalignant disorders. Blood. 2014;124:822–6.CrossRefPubMed
52.
53.
54.
Blum RW, Garell D, Hodgman CH, et al. Transition from child-centered to adult health-care systems for adolescents with chronic conditions. A position paper of the Society for Adolescent Medicine. J Adolesc Health. 1993;14:570–6.CrossRefPubMed
55.
Christie D, Viner R. Chronic illness and transition: time for action. Adolesc Med State Art Rev. 2009;20:981–7. xi PubMed
56.
Metadata
Title
Advances in the Care of Primary Immunodeficiencies (PIDs): from Birth to Adulthood
Authors
Nizar Mahlaoui
Klaus Warnatz
Alison Jones
Sarita Workman
Andrew Cant
Publication date
01-07-2017
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 5/2017
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-017-0401-y

Other articles of this Issue 5/2017

Journal of Clinical Immunology 5/2017 Go to the issue

Letter to Editor

Enterovirus-Related Immune Reconstitution Inflammatory Syndrome (IRIS) Following Haploidentical Stem Cell Transplantation in an MHC Class II-Deficient Child

Original Article

Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First Indian Patient and a Novel Deletion Affecting IL1RN

CME Review

Human IκBα Gain of Function: a Severe and Syndromic Immunodeficiency

Original Article

Common Variable Immunodeficiency Caused by FANC Mutations

Original Article

Identification of 22q11.2 Deletion Syndrome via Newborn Screening for Severe Combined Immunodeficiency

Original Article

Multicolor Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits