Skip to main content
Log in

Activated CD8+ T Cells and NKT Cells in BAL Fluid Improve Diagnostic Accuracy in Sarcoidosis

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Purpose

The clinical diagnosis of pulmonary sarcoidosis is based on the presence of noncaseating granulomas in an appropriate clinical setting with either bilateral hilar adenopathy and/or parenchymal infiltrates. Lymphocytosis with an increased CD4/CD8 T cell ratio in bronchoalveolar lavage fluid is supportive. We evaluated the diagnostic accuracy of a predictive binary logistic regression model in sarcoidosis based on sex, age, and bronchoalveolar lavage fluid cell profile with and without the inclusion of HLA-DR+ CD8+ T cells and natural killer T-cell fractions.

Methods

A retrospective analysis of differential cell counts and lymphocyte phenotypes by flow cytometry in bronchoalveolar lavage was performed in 183 patients investigated for possible diffuse parenchymal lung disease. A logistic regression model with age, sex, lymphocyte fraction, eosinophils, and CD4/CD8 ratio in bronchoalveolar lavage fluid (basic model) was compared with a final model, which also included fractions of HLA-DR+ CD8+ T cells and natural killer T cells. Diagnostic accuracy of the two models was assessed by receiver operating characteristic (ROC) curves.

Results

The area under the ROC curve for the basic and final model was 0.898 [95 % confidence interval (CI) 0.852–0.945] and 0.937 (95 % CI 0.902–0.972), respectively, p = 0.008.

Conclusions

Assessment of HLA-DR+ CD8+ T cell and natural killer T-cell fractions may improve diagnostic accuracy and further strengthen the importance of bronchoalveolar lavage in the diagnostic workup of sarcoidosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Wells AU, Hirani N (2008) Interstitial lung disease guideline. Thorax 63(Suppl 5):v1–v58. doi:10.1136/thx.2008.101691

    Article  PubMed  Google Scholar 

  2. Drent M, Mansour K, Linssen C (2007) Bronchoalveolar lavage in sarcoidosis. Semin Respir Crit Care Med 28(5):486–495

    Article  PubMed  Google Scholar 

  3. Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y (2003) Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 168(8):952–958

    Article  PubMed  Google Scholar 

  4. Cordeiro CR, Jones JC, Alfaro T, Ferreira AJ (2007) Bronchoalveolar lavage in occupational lung diseases. Semin Respir Crit Care Med 28(5):504–513

    Article  PubMed  Google Scholar 

  5. Meyer KC (2007) Bronchoalveolar lavage as a diagnostic tool. Semin Respir Crit Care Med 28(5):546–560. doi:10.1055/s-2007-991527

    Article  PubMed  Google Scholar 

  6. (1999) Statement on sarcoidosis. Am J Respir Crit Care Med 160(2):736–755

  7. Kantrow SP, Meyer KC, Kidd P, Raghu G (1997) The CD4/CD8 ratio in BAL fluid is highly variable in sarcoidosis. Eur Respir J 10(12):2716–2721

    Article  CAS  PubMed  Google Scholar 

  8. Meyer KC, Soergel P (1999) Variation of bronchoalveolar lymphocyte phenotypes with age in the physiologically normal human lung. Thorax 54(8):697–700

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Heron M, Claessen AME, Grutters JC, Van Den Bosch JMM (2010) T-cell activation profiles in different granulomatous interstitial lung diseases—a role for CD8+CD28null cells? Clin Exp Immunol 160(2):256–265. doi:10.1111/j.1365-2249.2009.04076.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Korosec P, Osolnik K, Kern I, Silar M, Mohorcic K, Kosnik M (2007) Expansion of pulmonary CD8+CD56+natural killer T cells in hypersensitivity pneumonitis*. Chest 132(4):1291–1297. doi:10.1378/chest.07-0128

    Article  PubMed  Google Scholar 

  11. Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years’ observation. Br Med J 2(5261):1165–1172

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Baughman RP (2007) Technical aspects of bronchoalveolar lavage: recommendations for a standard procedure. Semin Respir Crit Care Med 28(05):475–485. doi:10.1055/s-2007-991520

    Article  PubMed  Google Scholar 

  13. Albert A (1982) On the use and computation of likelihood ratios in clinical chemistry. Clin Chem 28(5):1113–1119

    CAS  PubMed  Google Scholar 

  14. Barry SM, Condez A, Johnson MA, Janossy G (2002) Determination of bronchoalveolar lavage leukocyte populations by flow cytometry in patients investigated for respiratory disease. Cytometry 50(6):291–297

    Article  PubMed  Google Scholar 

  15. Domagała-Kulawik J, Skirecki T, Maskey-Warzechowska M, Grubek-Jaworska H, Chazan R (2012) Bronchoalveolar lavage total cell count in interstitial lung diseases—does it matter? Inflammation 35(3):803–809. doi:10.1007/s10753-011-9378-5

    Article  PubMed  Google Scholar 

  16. Sauerbrei W, Royston P, Binder H (2007) Selection of important variables and determination of functional form for continuous predictors in multivariable model building. Stat Med 26(30):5512–5528

    Article  PubMed  Google Scholar 

  17. Metz CE (1978) Basic principles of ROC analysis. Semin Nucl Med 8(4):283–298

    Article  CAS  PubMed  Google Scholar 

  18. Moons KG, de Groot JA, Linnet K, Reitsma JB, Bossuyt PM (2012) Quantifying the added value of a diagnostic test or marker. Clin Chem 58(10):1408–1417. doi:10.1373/clinchem.2012.182550

    Article  PubMed  Google Scholar 

  19. Steyerberg EW, Harrell FE Jr, Borsboom GJJM, Eijkemans MJC, Vergouwe Y, Habbema JDF (2001) Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol 54(8):774–781. doi:10.1016/S0895-4356(01)00341-9

    Article  CAS  PubMed  Google Scholar 

  20. Hallan S, Asberg A, Edna TH (1997) Estimating the probability of acute appendicitis using clinical criteria of a structured record sheet: the physician against the computer. Eur J Surg 163(6):427–432

    CAS  PubMed  Google Scholar 

  21. Efron B (1982) 9. Random subsampling. In: The Jackknife, the bootstrap and other resampling plans. SIAM, Philadelphia, p 69–73. doi:10.1137/1.9781611970319.ch9

  22. DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):837–845

    Article  CAS  PubMed  Google Scholar 

  23. Meyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, du Bois RM, Drent M, Haslam PL, Kim DS, Nagai S, Rottoli P, Saltini C, Selman M, Strange C, Wood B (2012) An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 185(9):1004–1014

    Article  PubMed  Google Scholar 

  24. Drent M, van Nierop MA, Gerritsen FA, Wouters EF, Mulder PG (1996) A computer program using BALF-analysis results as a diagnostic tool in interstitial lung diseases. Am J Respir Crit Care Med 153(2):736–741

    Article  CAS  PubMed  Google Scholar 

  25. De Smet D, Martens GA, Berghe BV, Meysman M, Heylen O, Gorus FK, De Waele M (2010) Use of likelihood ratios improves interpretation of laboratory testing for pulmonary sarcoidosis. Am J Clin Pathol 134(6):939–947. doi:10.1309/ajcpnc7sthg0fwmp

    Article  PubMed  Google Scholar 

  26. Drent M, Jacobs JA, Cobben NA, Costabel U, Wouters EF, Mulder PG (2001) Computer program supporting the diagnostic accuracy of cellular BALF analysis: a new release. Respir Med 95(10):781–786

    Article  CAS  PubMed  Google Scholar 

  27. Li QH, Li HP, Shen YP, Zhao L, Shen L, Zhang Y, Jiang DH, Baughman RP (2012) A novel multi-parameter scoring system for distinguishing sarcoidosis from sputum negative tuberculosis. Sarcoidosis Vasc Diffuse Lung Dis 29(1):11–18

    PubMed  Google Scholar 

  28. Copas JB (1983) Regression, prediction and shrinkage. J R Stat Soc Ser B 45(3):311–354. doi:10.2307/2345402

    Google Scholar 

  29. Ho L-P, Urban BC, Thickett DR, Davies RJO, McMichael AJ (2005) Deficiency of a subset of T cells with immunoregulatory properties in sarcoidosis. Lancet 365(9464):1062–1072. doi:10.1016/s0140-6736(05)71143-0

    Article  CAS  PubMed  Google Scholar 

  30. Wajchman HJ, Pierce CW, Varma VA, Issa MM, Petros J, Dombrowski KE (2004) Ex vivo expansion of CD8+CD56+ and CD8+CD56− natural killer T cells specific for MUC1 mucin. Cancer Res 64(3):1171–1180. doi:10.1158/0008-5472.can-3254-2

    Article  CAS  PubMed  Google Scholar 

  31. Ødum N, Yoshizumi H, Okamoto Y, Kamikawaji N, Kimura A, Nishimura Y, Sasazuki T (1992) Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion. Human Immunol 35(2):71–84. doi:10.1016/0198-8859(92)90014-e

    Article  Google Scholar 

  32. Imamichi H, Lempicki RA, Adelsberger JW, Hasley RB, Rosenberg A, Roby G, Rehm CA, Nelson A, Krishnan S, Pavlick M, Woods CJ, Baseler MW, Lane HC (2012) The CD8+HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls. Eur J Immunol. doi:10.1002/eji.201142046

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Assistance provided by Gine Eggen and colleagues in the Unit for cytometry, Department of Immunology and Transfusion Medicine, St. Olavs University Hospital was greatly appreciated, and the unit’s expertise in flow cytometry has been invaluable to this study.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Tøndell.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tøndell, A., Rø, A.D., Åsberg, A. et al. Activated CD8+ T Cells and NKT Cells in BAL Fluid Improve Diagnostic Accuracy in Sarcoidosis. Lung 192, 133–140 (2014). https://doi.org/10.1007/s00408-013-9527-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-013-9527-8

Keywords

Navigation