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Journal of Clinical Immunology

, Volume 39, Issue 6, pp 569–576 | Cite as

Cellular Defects in CVID Patients with Chronic Lung Disease in the USIDNET Registry

  • Erinn S. KellnerEmail author
  • Ramsay Fuleihan
  • Charlotte Cunningham-Rundles
  • The USIDNET Consortium
  • Joshua B. WechslerEmail author
Original Article
  • 81 Downloads

Abstract

Purpose

Chronic lung disease is the most common cause of morbidity and mortality in patients with common variable immunodeficiency (CVID). While biomarkers exist to predict non-infectious complications, the unique features that define CVID patients with chronic lung disease are not well understood.

Methods

We analyzed data from CVID patients from the retrospective USIDNET (United States Immunodeficiency Network) patient database. Patients were categorized into 3 phenotypes for comparison: (1) CVID without chronic lung disease, (2) CVID with bronchiectasis only, and (3) CVID with interstitial lung disease (ILD) with or without bronchiectasis. Among these groups, differences were assessed in demographics, comorbidities, infections, treatments, and peripheral blood immune measures. We analyzed 1518 CVID patients which included 1233 (81.2%) without chronic lung disease, 147 (9.7%) with bronchiectasis only, and 138 (9.1%) with interstitial lung disease.

Results

Patients with ILD had lower CD3+ cell counts (P = .001), CD4+ cell counts (P < .05), and CD8+ cell counts (P < .001) compared with patients without lung disease. Additionally, there was significantly more CVID patients with ILD with pneumonia (P < .001), herpes viruses (P = .01) and fungal infections (P < .001) compared with patients with CVID without chronic lung disease.

Conclusion

This analysis suggests that patients with chronic lung disease may be more likely to have lower peripheral T cell counts and complications of those defects compared with CVID patients without chronic lung disease.

Keywords

Common variable immunodeficiency CVID granulomatous lymphocytic interstitial lung disease GLILD autoimmunity USIDNET 

Notes

Acknowledgements

We gratefully acknowledge Julie Magnusson, Marla Goldsmith, and Tara Caulder for their continued support with the USIDNET. We also acknowledge and thank all contributing physicians and patients. This work was partially supported by K08DK09772 (to JBW).

Authorship Contributions

ESK: Data collection, data interpretation, and manuscript preparation

RF: Critical review and co-investigator for USIDNET

CCR: Critical review and PI for USIDNET

JBW: Project supervision, data interpretation, and manuscript preparation

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38–59.  https://doi.org/10.1016/j.jaip.2015.07.025.CrossRefGoogle Scholar
  2. 2.
    Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85.  https://doi.org/10.1182/blood-2007-06-091744.CrossRefGoogle Scholar
  3. 3.
    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.  https://doi.org/10.1182/blood-2011-09-377945.CrossRefGoogle Scholar
  4. 4.
    Park J, Munagala I, Xu H, Blankenship D, Maffucci P, Chaussabel D, et al. Interferon signature in the blood in inflammatory common variable immune deficiency. PLoS One. 2013;8(9):e74893.  https://doi.org/10.1371/journal.pone.0074893.CrossRefGoogle Scholar
  5. 5.
    Fasano MB, Sullivan KE, Sarpong SB, Wood RA, Jones SM, Johns CJ, et al. Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature. Medicine (Baltimore). 1996;75(5):251–61.CrossRefGoogle Scholar
  6. 6.
    Rao N, Mackinnon AC, Routes JM. Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases. Hum Pathol. 2015;46(9):1306–14.  https://doi.org/10.1016/j.humpath.2015.05.011.CrossRefGoogle Scholar
  7. 7.
    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.  https://doi.org/10.1016/j.jaci.2004.05.057.CrossRefGoogle Scholar
  8. 8.
    Bateman EA, Ayers L, Sadler R, Lucas M, Roberts C, Woods A, et al. T cell phenotypes in patients with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections. Clin Exp Immunol. 2012;170(2):202–11.  https://doi.org/10.1111/j.1365-2249.2012.04643.x.CrossRefGoogle Scholar
  9. 9.
    Fevang B, Yndestad A, Sandberg WJ, Holm AM, Muller F, Aukrust P, et al. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin Exp Immunol. 2007;147(3):521–5.  https://doi.org/10.1111/j.1365-2249.2006.03314.x.CrossRefGoogle Scholar
  10. 10.
    Mouillot G, Carmagnat M, Gerard L, Garnier JL, Fieschi C, Vince N, et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010;30(5):746–55.  https://doi.org/10.1007/s10875-010-9424-3.CrossRefGoogle Scholar
  11. 11.
    Semenzato G. Immunology of interstitial lung diseases: cellular events taking place in the lung of sarcoidosis, hypersensitivity pneumonitis and HIV infection. Eur Respir J. 1991;4(1):94–102.Google Scholar
  12. 12.
    Crouser ED, Lozanski G, Fox CC, Hauswirth DW, Raveendran R, Julian MW. The CD4+ lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy. Chest. 2010;137(6):1432–5.  https://doi.org/10.1378/chest.09-2576.CrossRefGoogle Scholar
  13. 13.
    Ochtrop ML, Goldacker S, May AM, Rizzi M, Draeger R, Hauschke D, et al. T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood. 2011;118(2):309–18.  https://doi.org/10.1182/blood-2010-11-321695.CrossRefGoogle Scholar
  14. 14.
    Farrant J, Spickett G, Matamoros N, Copas D, Hernandez M, North M, et al. Study of B and T cell phenotypes in blood from patients with common variable immunodeficiency (CVID). Immunodeficiency. 1994;5(2):159–69.Google Scholar
  15. 15.
    Wong GK, Huissoon AP. T-cell abnormalities in common variable immunodeficiency: the hidden defect. J Clin Pathol. 2016;69(8):672–6.  https://doi.org/10.1136/jclinpath-2015-203351.CrossRefGoogle Scholar
  16. 16.
    Barbosa RR, Silva SP, Silva SL, Melo AC, Pedro E, Barbosa MP, et al. Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation. PLoS One. 2011;6(8):e22848.  https://doi.org/10.1371/journal.pone.0022848.CrossRefGoogle Scholar
  17. 17.
    Ganjalikhani-Hakemi M, Yazdani R, Sherkat R, Homayouni V, Masjedi M, Hosseini M. Evaluation of the T helper 17 cell specific genes and the innate lymphoid cells counts in the peripheral blood of patients with the common variable immunodeficiency. J Res Med Sci. 2014;19(Suppl 1):S30–5.Google Scholar
  18. 18.
    Unger S, Seidl M, van Schouwenburg P, Rakhmanov M, Bulashevska A, Frede N, et al. The TH1 phenotype of follicular helper T cells indicates an IFN-gamma-associated immune dysregulation in patients with CD21low common variable immunodeficiency. J Allergy Clin Immunol. 2018;141(2):730–40.  https://doi.org/10.1016/j.jaci.2017.04.041.CrossRefGoogle Scholar
  19. 19.
    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.  https://doi.org/10.1007/s10875-014-0068-6.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Allergy and Immunology, Department of MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Division of Allergy-ImmunologyAnn & Robert H. Lurie Children’s Hospital of ChicagoChicagoUSA
  3. 3.Division of Allergy and Immunology, Department of MedicineThe Icahn School of Medicine at Mount SinaiNew YorkUSA
  4. 4.Division of Gastroenterology, Hepatology & Nutrition, Department of PediatricsAnn & Robert H. Lurie Children’s Hospital of ChicagoChicagoUSA

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