Exploring noninfectious radiological lung findings in adult patients with primary immunodeficiency diseases
Main Article Content
Keywords
class-switched memory B cell, high-resolution computed tomography, lung, pulmonary function test, primary immunodeficiency
Abstract
Primary immunodeficiency diseases (PIDs) show different patterns of airway involvement, particularly bronchiectasis; however, comparative studies of radiologic manifestations in patients with PIDs are scarce. Hence, the aim of this study to investigate radiologic lung findings in adult patients with PIDs and evaluate the possible relationship between clinical and immunologic features and respiratory function in these patients. In this study, the demographic and clinical characteristics, serum immunoglobulins (Ig), lymphocyte subgroups, high-resolution computed tomography (HRCT), and pulmonary function tests (PFTs) of 116 adult patients with PID were evaluated and those with and without abnormal HRCT were compared. The median age was 40 (28–48) years, and there were 51 (44%) females. Abnormal findings were detected in 55.2% of the HRCTs, but the most common findings were bronchiectasis (30.2%), bilateral involvement (73.5%), and lower lobe predominance. The median age and age of diagnosis were higher in those with HRCT findings. The obstructive pattern was the most common found in the PFTs. Forced vital capacity, maximal mid-expiratory flow at 25–75%, immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), cluster of differentiation (CD)4+ T cell, CD4+/CD8+ ratio, and class-switched memory B (cSMB) cell levels were significantly lower, whereas mortality was higher. Noninfectious pulmonary complications are among the important causes of morbidity and mortality in PID that could result in chronic lung disease despite adequate Ig therapy. Considering the extra radiation dose of HRCT, clinical findings and immunological and PFT parameters accompanying radiological features may be helpful in predicting the diagnosis; it may also be useful in determining additional treatment modalities and reducing mortality.
References
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3 Grimbacher B, Party ERW. The European Society for Immunodeficiencies (ESID) registry 2014. Clin Exp Immunol. 2014;178(Suppl 1):18–20. 10.1111/cei.12496
4 Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of spirometry 2019 update. An official American Thoracic Society and European Respiratory Society technical statement. Am J Respir Crit Care Med. 2019;200(8):e70–88. 10.1164/rccm.201908-1590ST
5 Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human inborn errors of immunity: 2022 Update on the classification from the international union of immunological societies expert committee. J Clin Immunol. 2022;42(7):1473–507. 10.1007/s10875-022-01289-3
6 Blore J, Haeney MR. Primary antibody deficiency and diagnostic delay. BMJ. 1989;298(6672):516–7. 10.1136/bmj.298.6672.516
7 Thickett KM, Kumararatne DS, Banerjee AK, Dudley R, Stableforth DE. Common variable immune deficiency: Respiratory manifestations, pulmonary function and high-resolution CT scan findings. QJM. 2002;95(10):655–62. 10.1093/qjmed/95.10.655
8 Thalhammer J, Kindle G, Nieters A, Rusch S, Seppanen MRJ, Fischer A, et al. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations. J Allergy Clin Immunol. 2021;148(5):1332-41 e5.
9 Long A, Kleiner A, Looney RJ. Immune dysregulation. J Allergy Clin Immunol. 2023;151(1):70–80. 10.1016/j.jaci.2022.11.001
10 Jolles S, Sanchez-Ramon S, Quinti I, Soler-Palacin P, Agostini C, Florkin B, et al. Screening protocols to monitor respiratory status in primary immunodeficiency disease: Findings from a European survey and subclinical infection working group. Clin Exp Immunol. 2017;190(2):226–34. 10.1111/cei.13012
11 Cunningham-Rundles C. Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol. 1989;9(1):22–33. 10.1007/BF00917124
12 Cunningham-Rundles C. How I treat common variable immune deficiency. Blood. 2010;116(1):7–15. 10.1182/blood-2010-01-254417
13 Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: Clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34–48. 10.1006/clim.1999.4725
14 Turner PJ, Mehr S, Kemp AS. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol. 2011;22(4):449–50; author reply 51–2. 10.1111/j.1399-3038.2010.01118.x
15 Maarschalk-Ellerbroek LJ, de Jong PA, van Montfrans JM, Lammers JW, Bloem AC, Hoepelman AI, et al. CT screening for pulmonary pathology in common variable immunodeficiency disorders and the correlation with clinical and immunological parameters. J Clin Immunol. 2014;34(6):642–54. 10.1007/s10875-014-0068-6
16 Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16. 10.1007/s10875-007-9075-1
17 Baumann U, Routes JM, Soler-Palacin P, Jolles S. The lung in primary immunodeficiencies: New concepts in infection and inflammation. Front Immunol. 2018;9:1837. 10.3389/fimmu.2018.01837
18 Gupta S, Pattanaik D, Krishnaswamy G. Common variable immune deficiency and associated complications. Chest. 2019;156(3):579–93. 10.1016/j.chest.2019.05.009
19 Grenier PA, Brun AL, Longchampt E, Lipski M, Mellot F, Catherinot E. Primary immunodeficiency diseases of adults: A review of pulmonary complication imaging findings. Eur Radiol. 2024;34(6):4142–54. 10.1007/s00330-023-10334-7
20 Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114(2):415–21. 10.1016/j.jaci.2004.05.057
21 Costa-Carvalho BT, Wandalsen GF, Pulici G, Aranda CS, Sole D. Pulmonary complications in patients with antibody deficiency. Allergol Immunopathol (Madr). 2011;39(3):128–32. 10.1016/j.aller.2010.12.003
22 Movahedi M, Jamee M, Ghaffaripour H, Noori F, Ghaini M, Eskandarzadeh S, et al. Pulmonary manifestations in a cohort of patients with inborn errors of immunity: An 8-year follow-up study. Allergol Immunopathol (Madr). 2022;50(1):80–4. 10.15586/aei.v50i1.388
23 Bierry G, Boileau J, Barnig C, Gasser B, Korganow AS, Buy X, et al. Thoracic manifestations of primary humoral immunodeficiency: A comprehensive review. Radiographics. 2009;29(7):1909–20.
24 Barbosa M, Chalmers JD. Bronchiectasis. Presse Med. 2023;52(3):104174. 10.1016/j.lpm.2023.104174
25 Goussault H, Salvator H, Catherinot E, Chabi ML, Tcherakian C, Chabrol A, et al. Primary immunodeficiency-related bronchiectasis in adults: Comparison with bronchiectasis of other etiologies in a French reference center. Respir Res. 2019;20(1):275. 10.1186/s12931-019-1242-4
26 van de Ven AA, de Jong PA, Hoytema van Konijnenburg DP, Kessels OA, Boes M, Sanders EA, et al. Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency. Clin Exp Immunol. 2011;165(2):235–42. 10.1111/j.1365-2249.2011.04425.x
27 van de Ven AA, van Montfrans JM, Terheggen-Lagro SW, Beek FJ, Hoytema van Konijnenburg DP, Kessels OA, et al. A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. Chest. 2010;138(2):371–9. 10.1378/chest.09-2398
28 Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5(Suppl A):S225–33. 10.1016/S1526-0542(04)90043-7
29 Baumann U, Gocke K, Gewecke B, Freihorst J, von Specht BU. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: A clinical phase I/II study. Respir Res. 2007;8(1):57. 10.1186/1465-9921-8-57
30 Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol. 2011;29:273–93. 10.1146/annurev-immunol-031210-101317
31 Twigg HL, 3rd. Humoral immune defense (antibodies): Recent advances. Proc Am Thorac Soc. 2005;2(5):417–21. 10.1513/pats.200508-089JS
32 Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: Results from a multicenter prospective cohort study. J Clin Immunol. 2011;31(3):315–22. 10.1007/s10875-011-9511-0
33 Park JE, Beal I, Dilworth JP, Tormey V, Haddock J. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency. Eur J Radiol. 2005;54(3):359–64. 10.1016/j.ejrad.2004.09.005
34 Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med. 1997;127(8 Pt 1):613–7. 10.7326/0003-4819-127-8_Part_1-199710150-00005
35 Touw CM, van de Ven AA, de Jong PA, Terheggen-Lagro S, Beek E, Sanders EA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol. 2010;21(5):793–805. 10.1111/j.1399-3038.2009.00963.x
36 Landau LI, Phelan PD. The spectrum of cystic fibrosis: A study of pulmonary mechanics in 46 patients. Am Rev Respir Dis. 1973;108(3):593–602.
37 Chen Y, Stirling RG, Paul E, Hore-Lacy F, Thompson BR, Douglass JA. Longitudinal decline in lung function in patients with primary immunoglobulin deficiencies. J Allergy Clin Immunol. 2011;127(6):1414–7. 10.1016/j.jaci.2011.03.041
38 Rich AL, Le Jeune IR, McDermott L, Kinnear WJ. Serial lung function tests in primary immune deficiency. Clin Exp Immunol. 2008;151(1):110–3. 10.1111/j.1365-2249.2007.03550.x
39 Alachkar H, Taubenheim N, Haeney MR, Durandy A, Arkwright PD. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol. 2006;120(3):310–8. 10.1016/j.clim.2006.05.003
40 Detkova D, de Gracia J, Lopes-da-Silva S, Vendrell M, Alvarez A, Guarner L, et al. Common variable immunodeficiency: Association between memory B cells and lung diseases. Chest. 2007;131(6):1883–9. 10.1378/chest.06-2994
41 Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7. 10.1182/blood-2011-09-377945
42 Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: Division into distinct clinical phenotypes. Blood. 2008;112(2):277–86. 10.1182/blood-2007-11-124545
43 The United States Immunodeficiency Network (USIDNET) webpage [Available from: https://usidnet.org/registry-data/stats-registry-enrollment/.
44 ESID Registry Network Reporting Tool public webpage Available from: https://cci-reporting.uniklinik-freiburg.de/#/.
45 Aghamohammadi A, Rezaei N, Yazdani R, Delavari S, Kutukculer N, Topyildiz E, et al. Consensus Middle East and North Africa registry on inborn errors of immunity. J Clin Immunol. 2021;41(6):1339–51. 10.1007/s10875-021-01053-z
2 Jesenak M, Banovcin P, Jesenakova B, Babusikova E. Pulmonary manifestations of primary immunodeficiency disorders in children. Front Pediatr. 2014;2:77. 10.3389/fped.2014.00077
3 Grimbacher B, Party ERW. The European Society for Immunodeficiencies (ESID) registry 2014. Clin Exp Immunol. 2014;178(Suppl 1):18–20. 10.1111/cei.12496
4 Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of spirometry 2019 update. An official American Thoracic Society and European Respiratory Society technical statement. Am J Respir Crit Care Med. 2019;200(8):e70–88. 10.1164/rccm.201908-1590ST
5 Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human inborn errors of immunity: 2022 Update on the classification from the international union of immunological societies expert committee. J Clin Immunol. 2022;42(7):1473–507. 10.1007/s10875-022-01289-3
6 Blore J, Haeney MR. Primary antibody deficiency and diagnostic delay. BMJ. 1989;298(6672):516–7. 10.1136/bmj.298.6672.516
7 Thickett KM, Kumararatne DS, Banerjee AK, Dudley R, Stableforth DE. Common variable immune deficiency: Respiratory manifestations, pulmonary function and high-resolution CT scan findings. QJM. 2002;95(10):655–62. 10.1093/qjmed/95.10.655
8 Thalhammer J, Kindle G, Nieters A, Rusch S, Seppanen MRJ, Fischer A, et al. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations. J Allergy Clin Immunol. 2021;148(5):1332-41 e5.
9 Long A, Kleiner A, Looney RJ. Immune dysregulation. J Allergy Clin Immunol. 2023;151(1):70–80. 10.1016/j.jaci.2022.11.001
10 Jolles S, Sanchez-Ramon S, Quinti I, Soler-Palacin P, Agostini C, Florkin B, et al. Screening protocols to monitor respiratory status in primary immunodeficiency disease: Findings from a European survey and subclinical infection working group. Clin Exp Immunol. 2017;190(2):226–34. 10.1111/cei.13012
11 Cunningham-Rundles C. Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol. 1989;9(1):22–33. 10.1007/BF00917124
12 Cunningham-Rundles C. How I treat common variable immune deficiency. Blood. 2010;116(1):7–15. 10.1182/blood-2010-01-254417
13 Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: Clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34–48. 10.1006/clim.1999.4725
14 Turner PJ, Mehr S, Kemp AS. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol. 2011;22(4):449–50; author reply 51–2. 10.1111/j.1399-3038.2010.01118.x
15 Maarschalk-Ellerbroek LJ, de Jong PA, van Montfrans JM, Lammers JW, Bloem AC, Hoepelman AI, et al. CT screening for pulmonary pathology in common variable immunodeficiency disorders and the correlation with clinical and immunological parameters. J Clin Immunol. 2014;34(6):642–54. 10.1007/s10875-014-0068-6
16 Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16. 10.1007/s10875-007-9075-1
17 Baumann U, Routes JM, Soler-Palacin P, Jolles S. The lung in primary immunodeficiencies: New concepts in infection and inflammation. Front Immunol. 2018;9:1837. 10.3389/fimmu.2018.01837
18 Gupta S, Pattanaik D, Krishnaswamy G. Common variable immune deficiency and associated complications. Chest. 2019;156(3):579–93. 10.1016/j.chest.2019.05.009
19 Grenier PA, Brun AL, Longchampt E, Lipski M, Mellot F, Catherinot E. Primary immunodeficiency diseases of adults: A review of pulmonary complication imaging findings. Eur Radiol. 2024;34(6):4142–54. 10.1007/s00330-023-10334-7
20 Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114(2):415–21. 10.1016/j.jaci.2004.05.057
21 Costa-Carvalho BT, Wandalsen GF, Pulici G, Aranda CS, Sole D. Pulmonary complications in patients with antibody deficiency. Allergol Immunopathol (Madr). 2011;39(3):128–32. 10.1016/j.aller.2010.12.003
22 Movahedi M, Jamee M, Ghaffaripour H, Noori F, Ghaini M, Eskandarzadeh S, et al. Pulmonary manifestations in a cohort of patients with inborn errors of immunity: An 8-year follow-up study. Allergol Immunopathol (Madr). 2022;50(1):80–4. 10.15586/aei.v50i1.388
23 Bierry G, Boileau J, Barnig C, Gasser B, Korganow AS, Buy X, et al. Thoracic manifestations of primary humoral immunodeficiency: A comprehensive review. Radiographics. 2009;29(7):1909–20.
24 Barbosa M, Chalmers JD. Bronchiectasis. Presse Med. 2023;52(3):104174. 10.1016/j.lpm.2023.104174
25 Goussault H, Salvator H, Catherinot E, Chabi ML, Tcherakian C, Chabrol A, et al. Primary immunodeficiency-related bronchiectasis in adults: Comparison with bronchiectasis of other etiologies in a French reference center. Respir Res. 2019;20(1):275. 10.1186/s12931-019-1242-4
26 van de Ven AA, de Jong PA, Hoytema van Konijnenburg DP, Kessels OA, Boes M, Sanders EA, et al. Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency. Clin Exp Immunol. 2011;165(2):235–42. 10.1111/j.1365-2249.2011.04425.x
27 van de Ven AA, van Montfrans JM, Terheggen-Lagro SW, Beek FJ, Hoytema van Konijnenburg DP, Kessels OA, et al. A CT scan score for the assessment of lung disease in children with common variable immunodeficiency disorders. Chest. 2010;138(2):371–9. 10.1378/chest.09-2398
28 Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5(Suppl A):S225–33. 10.1016/S1526-0542(04)90043-7
29 Baumann U, Gocke K, Gewecke B, Freihorst J, von Specht BU. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: A clinical phase I/II study. Respir Res. 2007;8(1):57. 10.1186/1465-9921-8-57
30 Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol. 2011;29:273–93. 10.1146/annurev-immunol-031210-101317
31 Twigg HL, 3rd. Humoral immune defense (antibodies): Recent advances. Proc Am Thorac Soc. 2005;2(5):417–21. 10.1513/pats.200508-089JS
32 Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: Results from a multicenter prospective cohort study. J Clin Immunol. 2011;31(3):315–22. 10.1007/s10875-011-9511-0
33 Park JE, Beal I, Dilworth JP, Tormey V, Haddock J. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency. Eur J Radiol. 2005;54(3):359–64. 10.1016/j.ejrad.2004.09.005
34 Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med. 1997;127(8 Pt 1):613–7. 10.7326/0003-4819-127-8_Part_1-199710150-00005
35 Touw CM, van de Ven AA, de Jong PA, Terheggen-Lagro S, Beek E, Sanders EA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol. 2010;21(5):793–805. 10.1111/j.1399-3038.2009.00963.x
36 Landau LI, Phelan PD. The spectrum of cystic fibrosis: A study of pulmonary mechanics in 46 patients. Am Rev Respir Dis. 1973;108(3):593–602.
37 Chen Y, Stirling RG, Paul E, Hore-Lacy F, Thompson BR, Douglass JA. Longitudinal decline in lung function in patients with primary immunoglobulin deficiencies. J Allergy Clin Immunol. 2011;127(6):1414–7. 10.1016/j.jaci.2011.03.041
38 Rich AL, Le Jeune IR, McDermott L, Kinnear WJ. Serial lung function tests in primary immune deficiency. Clin Exp Immunol. 2008;151(1):110–3. 10.1111/j.1365-2249.2007.03550.x
39 Alachkar H, Taubenheim N, Haeney MR, Durandy A, Arkwright PD. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol. 2006;120(3):310–8. 10.1016/j.clim.2006.05.003
40 Detkova D, de Gracia J, Lopes-da-Silva S, Vendrell M, Alvarez A, Guarner L, et al. Common variable immunodeficiency: Association between memory B cells and lung diseases. Chest. 2007;131(6):1883–9. 10.1378/chest.06-2994
41 Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7. 10.1182/blood-2011-09-377945
42 Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: Division into distinct clinical phenotypes. Blood. 2008;112(2):277–86. 10.1182/blood-2007-11-124545
43 The United States Immunodeficiency Network (USIDNET) webpage [Available from: https://usidnet.org/registry-data/stats-registry-enrollment/.
44 ESID Registry Network Reporting Tool public webpage Available from: https://cci-reporting.uniklinik-freiburg.de/#/.
45 Aghamohammadi A, Rezaei N, Yazdani R, Delavari S, Kutukculer N, Topyildiz E, et al. Consensus Middle East and North Africa registry on inborn errors of immunity. J Clin Immunol. 2021;41(6):1339–51. 10.1007/s10875-021-01053-z
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May 1, 2025
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Sadi Aykan, F., Çölkesen, F., Evcen, R., Kılınç, M., Yıldız, E., Yılmaz Ergün, Ümmügülsüm, Önalan, T., Akkuş, F. A., Emin Gerek, M., & Arslan, Şevket. (2025). Exploring noninfectious radiological lung findings in adult patients with primary immunodeficiency diseases (S. Kahraman , Trans.). Allergologia Et Immunopathologia, 53(3), 41-50. https://doi.org/10.15586/aei.v53i3.1302
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Sadi Aykan, F., Çölkesen, F., Evcen, R., Kılınç, M., Yıldız, E., Yılmaz Ergün, Ümmügülsüm, Önalan, T., Akkuş, F. A., Emin Gerek, M., & Arslan, Şevket. (2025). Exploring noninfectious radiological lung findings in adult patients with primary immunodeficiency diseases (S. Kahraman , Trans.). Allergologia Et Immunopathologia, 53(3), 41-50. https://doi.org/10.15586/aei.v53i3.1302