Semin Respir Crit Care Med 2021; 42(04): 525-536
DOI: 10.1055/s-0041-1730893
Review Article

Common Variable Immunodeficiency and Other Immunodeficiency Syndromes in Bronchiectasis

Pamela J. McShane
1   Section of Pulmonary and Critical Care Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas
› Author Affiliations

Abstract

Immunodeficiency represents a vast number of diseases and syndromes. Both primary and secondary forms of immunodeficiency are important contributors to the development of bronchiectasis. Primary immune deficiencies, in particular, are increasingly identified and defined as contributors. Specific immune deficiencies that are closely associated with bronchiectasis and as discussed in this article are common variable immunodeficiency, specific antibody deficiency, immunodeficiencies involving immunoglobulin E, DOCK8 immunodeficiency, phosphoglucomutase 3 deficiency, activated phosphoinositide 3-kinase delta syndrome, and X-linked agammaglobulinemia. Each of these primary immune deficiencies has unique nuances. Vigilance for these unique signs and symptoms is likely to improve recognition of specific immunodeficiency in the idiopathic bronchiectasis patient. Secondary forms of immunodeficiency occur as a result of a separate disease process. Graft versus host disease, malignancy, and human immunodeficiency virus are three classic examples discussed in this article. An awareness of the potential for these disease settings to lead to bronchiectasis is necessary to optimize patient care. With understanding and mindfulness toward the intricate relationship between bronchiectasis and immunodeficiency, there is an opportunity to elucidate pathophysiologic underpinnings between these two syndromes.



Publication History

Article published online:
14 July 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Cole PJ. Inflammation: a two-edged sword--the model of bronchiectasis. Eur J Respir Dis Suppl 1986; 147: 6-15
  • 2 Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet 2018; 392 (10150): 880-890
  • 3 Polverino E, Goeminne PC, McDonnell MJ. et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J 2017; 50 (03) 50
  • 4 Chang AB, Bell SC, Torzillo PJ. et al; Extended Voting Group. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand Thoracic Society of Australia and New Zealand guidelines. Med J Aust 2015; 202 (03) 130
  • 5 Pasteur MC, Bilton D, Hill AT. British Thoracic Society Bronchiectasis Non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010; 65 (Suppl. 01) i1-i58
  • 6 Tangye SG, Al-Herz W, Bousfiha A. et al. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2020; 40 (01) 24-64
  • 7 Sullivan KE, Puck JM, Notarangelo LD. et al. USIDNET: a strategy to build a community of clinical immunologists. J Clin Immunol 2014; 34 (04) 428-435
  • 8 Seidel MG, Kindle G, Gathmann B. et al; ESID Registry Working Party and collaborators. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract 2019; 7 (06) 1763-1770
  • 9 Cooper MD, Faulk WP, Fudenberg HH. et al. Classification of primary immunodeficiencies. N Engl J Med 1973; 288 (18) 966-967
  • 10 Fudenberg H, Good RA, Goodman HC. et al. Primary immunodeficiencies. Report of a World Health Organization Committee. Pediatrics 1971; 47 (05) 927-946
  • 11 Notarangelo LD, Fischer A, Geha RS. et al; International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol 2009; 124 (06) 1161-1178
  • 12 Conley ME, Notarangelo LD, Etzioni A. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Diagnostic criteria for primary immunodeficiencies. Clin Immunol 1999; 93 (03) 190-197
  • 13 Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immunodeficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol 2013; 174 (02) 203-211
  • 14 Bonilla FA, Barlan I, Chapel H. et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract 2016; 4 (01) 38-59
  • 15 Modell V, Orange JS, Quinn J, Modell F. Global report on primary immunodeficiencies: 2018 update from the Jeffrey Modell Centers Network on disease classification, regional trends, treatment modalities, and physician reported outcomes. Immunol Res 2018; 66 (03) 367-380
  • 16 Oksenhendler E, Gérard L, Fieschi C. et al; DEFI Study Group. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis 2008; 46 (10) 1547-1554
  • 17 Ardeniz O, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Clin Immunol 2009; 133 (02) 198-207
  • 18 Kainulainen L, Nikoskelainen J, Ruuskanen O. Diagnostic findings in 95 Finnish patients with common variable immunodeficiency. J Clin Immunol 2001; 21 (02) 145-149
  • 19 Patrawala M, Cui Y, Peng L. et al. Pulmonary disease burden in primary immunodeficiency disorders: data from USIDNET Registry. J Clin Immunol 2020; 40 (02) 340-349
  • 20 Weinberger T, Fuleihan R, Cunningham-Rundles C, Maglione PJ. Factors beyond lack of antibody govern pulmonary complications in primary antibody deficiency. J Clin Immunol 2019; 39 (04) 440-447
  • 21 Maglione PJ, Overbey JR, Radigan L, Bagiella E, Cunningham-Rundles C. Pulmonary radiologic findings in common variable immunodeficiency: clinical and immunological correlations. Ann Allergy Asthma Immunol 2014; 113 (04) 452-459
  • 22 Eden E, Choate R, Barker A. et al. The clinical features of bronchiectasis associated with alpha-1 antitrypsin deficiency, common variable immunodeficiency and primary ciliary dyskinesia--results from the U.S. Bronchiectasis Research Registry. Chronic Obstr Pulm Dis (Miami) 2019; 6 (02) 145-153
  • 23 Chalmers JD, Goeminne P, Aliberti S. et al. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med 2014; 189 (05) 576-585
  • 24 Martínez-García MA, de Gracia J, Vendrell Relat M. et al. Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score. Eur Respir J 2014; 43 (05) 1357-1367
  • 25 Lonni S, Chalmers JD, Goeminne PC. et al. Etiology of non-cystic fibrosis bronchiectasis in adults and its correlation to disease severity. Ann Am Thorac Soc 2015; 12 (12) 1764-1770
  • 26 Qi Q, Wang W, Li T, Zhang Y, Li Y. Aetiology and clinical characteristics of patients with bronchiectasis in a Chinese Han population: a prospective study. Respirology 2015; 20 (06) 917-924
  • 27 Guan WJ, Gao YH, Xu G. et al. Aetiology of bronchiectasis in Guangzhou, southern China. Respirology 2015; 20 (05) 739-748
  • 28 Lee JVA, Chotirmall S. Etiology and microbiological profile of bronchiectasis in adults. Am J Respir Crit Care Med 2018; 197: A1975
  • 29 Visser SK, Bye PTP, Fox GJ. et al. Australian adults with bronchiectasis: the first report from the Australian Bronchiectasis Registry. Respir Med 2019; 155: 97-103
  • 30 Dhar R, Singh S, Talwar D. et al. Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry. Lancet Glob Health 2019; 7 (09) e1269-e1279
  • 31 Picard C, Bobby Gaspar H, Al-Herz W. et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol 2018; 38 (01) 96-128
  • 32 Orange JS, Ballow M, Stiehm ER. et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 2012; 130 (3, Suppl): S1-S24
  • 33 Keswani A, Dunn NM, Manzur A. et al. The clinical significance of specific antibody deficiency (SAD) severity in chronic rhinosinusitis (CRS). J Allergy Clin Immunol Pract 2017; 5 (04) 1105-1111
  • 34 Vendrell M, de Gracia J, Rodrigo MJ. et al. Antibody production deficiency with normal IgG levels in bronchiectasis of unknown etiology. Chest 2005; 127 (01) 197-204
  • 35 van Kessel DA, van Velzen-Blad H, van den Bosch JMM, Rijkers GT. Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology. Eur Respir J 2005; 25 (03) 482-489
  • 36 Freeman AF, Olivier KN. Hyper-IgE syndromes and the lung. Clin Chest Med 2016; 37 (03) 557-567
  • 37 Davis SD, Schaller J, Wedgwood RJ. Job's syndrome. Recurrent, “cold”, staphylococcal abscesses. Lancet 1966; 1 (7445): 1013-1015
  • 38 Freeman AF, Kleiner DE, Nadiminti H. et al. Causes of death in hyper-IgE syndrome. J Allergy Clin Immunol 2007; 119 (05) 1234-1240
  • 39 Freeman AF, Renner ED, Henderson C. et al. Lung parenchyma surgery in autosomal dominant hyper-IgE syndrome. J Clin Immunol 2013; 33 (05) 896-902
  • 40 Biggs CM, Keles S, Chatila TA. DOCK8 deficiency: insights into pathophysiology, clinical features and management. Clin Immunol 2017; 181: 75-82
  • 41 Su HC, Jing H, Angelus P, Freeman AF. Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome. Immunol Rev 2019; 287 (01) 9-19
  • 42 Zhang Q, Dove CG, Hor JL. et al. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity. J Exp Med 2014; 211 (13) 2549-2566
  • 43 Pillay BA, Avery DT, Smart JM. et al. Hematopoietic stem cell transplant effectively rescues lymphocyte differentiation and function in DOCK8-deficient patients. JCI Insight 2019; 5: 5
  • 44 Sassi A, Lazaroski S, Wu G. et al. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels. J Allergy Clin Immunol 2014; 133 (05) 1410-1419 , 1419.e1–1419.e13
  • 45 Zhang Y, Yu X, Ichikawa M. et al. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immunodeficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immunol 2014; 133 (05) 1400-1409 , 1409.e1–1409.e5
  • 46 Pacheco-Cuéllar G, Gauthier J, Désilets V. et al. A novel PGM3 mutation is associated with a severe phenotype of bone marrow failure, severe combined immunodeficiency, skeletal dysplasia, and congenital malformations. J Bone Miner Res 2017; 32 (09) 1853-1859
  • 47 Freeman AF, Milner JD. The child with elevated IgE and infection susceptibility. Curr Allergy Asthma Rep 2020; 20 (11) 65
  • 48 Angulo I, Vadas O, Garçon F. et al. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science 2013; 342 (6160): 866-871
  • 49 Lucas CL, Kuehn HS, Zhao F. et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol 2014; 15 (01) 88-97
  • 50 Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K. PI3Kδ and primary immunodeficiencies. Nat Rev Immunol 2016; 16 (11) 702-714
  • 51 Michalovich D, Nejentsev S. Activated PI3 kinase delta syndrome: from genetics to therapy. Front Immunol 2018; 9: 369
  • 52 Elkaim E, Neven B, Bruneau J. et al. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: a cohort study. J Allergy Clin Immunol 2016; 138 (01) 210-218
  • 53 Coulter TI, Chandra A, Bacon CM. et al. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: a large patient cohort study. J Allergy Clin Immunol 2017; 139 (02) 597-606
  • 54 Bruton OC. Agammaglobulinemia. Pediatrics 1952; 9 (06) 722-728
  • 55 Vetrie D, Vorechovský I, Sideras P. et al. The gene involved in X-linked agammaglobulinaemia is a member of the Src family of protein-tyrosine kinases. Nature 1993; 361 (6409): 226-233
  • 56 Tsukada S, Saffran DC, Rawlings DJ. et al. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993; 72 (02) 279-290
  • 57 Winkelstein JA, Marino MC, Lederman HM. et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore) 2006; 85 (04) 193-202
  • 58 Shillitoe B, Bangs C, Guzman D. et al. The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017. Clin Exp Immunol 2018; 192 (03) 284-291
  • 59 Ochs HD, Smith CI. X-linked agammaglobulinemia. A clinical and molecular analysis. Medicine (Baltimore) 1996; 75 (06) 287-299
  • 60 Plebani A, Soresina A, Rondelli R. et al; Italian Pediatric Group for XLA-AIEOP. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol 2002; 104 (03) 221-230
  • 61 Bryan BA, Battersby A, Shillitoe BM. et al. Respiratory health and related quality of life in patients with congenital agammaglobulinemia in the Northern Region of the UK. J Clin Immunol 2016; 36 (05) 472-479
  • 62 Shillitoe B, Gennery A. X-linked agammaglobulinaemia: outcomes in the modern era. Clin Immunol 2017; 183: 54-62
  • 63 Filipovich AH, Weisdorf D, Pavletic S. et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11 (12) 945-956
  • 64 Labžentytė V, Zemnickienė S, Danila E, Šileikienė V, Zablockis R, Gruslys V. A fast and fatal course of bronchiectasis: an unusual rare expression of chronic graft versus host disease: a case report. Acta Med Litu 2016; 23 (01) 54-59
  • 65 Phatak TD, Maldjian PD. Progressive bronchiectasis as a manifestation of chronic graft versus host disease following bone marrow transplantation. Radiol Case Rep 2015; 3 (01) 137
  • 66 Bhatia S, Francisco L, Carter A. et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood 2007; 110 (10) 3784-3792
  • 67 Hildebrandt GC, Fazekas T, Lawitschka A. et al. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transplant 2011; 46 (10) 1283-1295
  • 68 Couriel D, Carpenter PA, Cutler C. et al. Ancillary therapy and supportive care of chronic graft-versus-host disease: national institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report. Biol Blood Marrow Transplant 2006; 12 (04) 375-396
  • 69 Bergeron A, Belle A, Chevret S. et al. Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 39 (09) 547-553
  • 70 Bashoura L, Gupta S, Jain A. et al. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41 (01) 63-67
  • 71 Sicras-Mainar A, de Abajo FJ, Izquierdo-Alonso JL. Clinical and economic consequences of inhaled corticosteroid doses and particle size in triple inhalation therapy for COPD: real-life study. Int J Chron Obstruct Pulmon Dis 2020; 15: 3291-3302
  • 72 Andréjak C, Nielsen R, Thomsen VO, Duhaut P, Sørensen HT, Thomsen RW. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax 2013; 68 (03) 256-262
  • 73 Greer M, Berastegui C, Jaksch P. et al. Lung transplantation after allogeneic stem cell transplantation: a pan-European experience. Eur Respir J 2018; 51 (02) 51
  • 74 González D, van der Burg M, García-Sanz R. et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood 2007; 110 (09) 3112-3121
  • 75 Hallek M, Shanafelt TD, Eichhorst B. Chronic lymphocytic leukaemia. Lancet 2018; 391 (10129): 1524-1537
  • 76 Yogi S, Yamashiro T, Kamiya H. et al. Thoracic manifestations of adult T-cell leukemia/lymphoma on chest CT: difference between clinical subtypes. Diagn Interv Radiol 2019; 25 (01) 55-61
  • 77 Okada F, Ando Y, Kondo Y, Matsumoto S, Maeda T, Mori H. Thoracic CT findings of adult T-cell leukemia or lymphoma. AJR Am J Roentgenol 2004; 182 (03) 761-767
  • 78 Zaman M, Huissoon A, Buckland M. et al. Clinical and laboratory features of seventy-eight UK patients with Good's syndrome (thymoma and hypogammaglobulinaemia). Clin Exp Immunol 2019; 195 (01) 132-138
  • 79 Iyengar S, Harrison J, Richman P. Relapsed B-CLL/small B-lymphocytic lymphoma presenting as bronchiectasis. Eur J Haematol 2007; 79 (03) 274-275
  • 80 Dragic T, Litwin V, Allaway GP. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996; 381 (6584): 667-673
  • 81 Quinn TC. Acute primary HIV infection. JAMA 1997; 278 (01) 58-62
  • 82 Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med 1998; 339 (01) 33-39
  • 83 Cilloniz C, Torres A, Polverino E. et al. Community-acquired lung respiratory infections in HIV-infected patients: microbial aetiology and outcome. Eur Respir J 2014; 43 (06) 1698-1708
  • 84 Anwar GA, McDonnell MJ, Worthy SA. et al. Phenotyping adults with non-cystic fibrosis bronchiectasis: a prospective observational cohort study. Respir Med 2013; 107 (07) 1001-1007
  • 85 Buscot M, Pottier H, Marquette CH, Leroy S. Phenotyping adults with non-cystic fibrosis bronchiectasis: a 10-year cohort study in a French Regional University Hospital Center. Respiration 2016; 92 (01) 1-8
  • 86 Berman DM, Mafut D, Djokic B, Scott G, Mitchell C. Risk factors for the development of bronchiectasis in HIV-infected children. Pediatr Pulmonol 2007; 42 (10) 871-875
  • 87 Hensley-McBain T, Klatt NR. The dual role of neutrophils in HIV infection. Curr HIV/AIDS Rep 2018; 15 (01) 1-10
  • 88 Bedi P, Davidson DJ, McHugh BJ, Rossi AG, Hill AT. Blood neutrophils are reprogrammed in bronchiectasis. Am J Respir Crit Care Med 2018; 198 (07) 880-890
  • 89 Giam YH, Shoemark A, Chalmers JD. Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism. Eur Respir J 2021; 2003157
  • 90 Perez EE, Orange JS, Bonilla F. et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol 2017; 139 (3S): S1-S46
  • 91 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 (06) 1354-1360