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Erschienen in: Lung 1/2014

01.02.2014

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

verfasst von: A. Tøndell, A. D. Rø, A. Åsberg, M. Børset, T. Moen, M. Sue-Chu

Erschienen in: Lung | Ausgabe 1/2014

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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.
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Literatur
2.
Zurück zum Zitat Drent M, Mansour K, Linssen C (2007) Bronchoalveolar lavage in sarcoidosis. Semin Respir Crit Care Med 28(5):486–495CrossRefPubMed Drent M, Mansour K, Linssen C (2007) Bronchoalveolar lavage in sarcoidosis. Semin Respir Crit Care Med 28(5):486–495CrossRefPubMed
3.
Zurück zum Zitat 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):952–958CrossRefPubMed 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):952–958CrossRefPubMed
4.
Zurück zum Zitat Cordeiro CR, Jones JC, Alfaro T, Ferreira AJ (2007) Bronchoalveolar lavage in occupational lung diseases. Semin Respir Crit Care Med 28(5):504–513CrossRefPubMed Cordeiro CR, Jones JC, Alfaro T, Ferreira AJ (2007) Bronchoalveolar lavage in occupational lung diseases. Semin Respir Crit Care Med 28(5):504–513CrossRefPubMed
6.
Zurück zum Zitat (1999) Statement on sarcoidosis. Am J Respir Crit Care Med 160(2):736–755 (1999) Statement on sarcoidosis. Am J Respir Crit Care Med 160(2):736–755
7.
Zurück zum Zitat 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):2716–2721CrossRefPubMed 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):2716–2721CrossRefPubMed
8.
Zurück zum Zitat Meyer KC, Soergel P (1999) Variation of bronchoalveolar lymphocyte phenotypes with age in the physiologically normal human lung. Thorax 54(8):697–700PubMedCentralCrossRefPubMed Meyer KC, Soergel P (1999) Variation of bronchoalveolar lymphocyte phenotypes with age in the physiologically normal human lung. Thorax 54(8):697–700PubMedCentralCrossRefPubMed
10.
11.
Zurück zum Zitat Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years’ observation. Br Med J 2(5261):1165–1172PubMedCentralCrossRefPubMed Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years’ observation. Br Med J 2(5261):1165–1172PubMedCentralCrossRefPubMed
13.
Zurück zum Zitat Albert A (1982) On the use and computation of likelihood ratios in clinical chemistry. Clin Chem 28(5):1113–1119PubMed Albert A (1982) On the use and computation of likelihood ratios in clinical chemistry. Clin Chem 28(5):1113–1119PubMed
14.
Zurück zum Zitat 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):291–297CrossRefPubMed 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):291–297CrossRefPubMed
15.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
16.
Zurück zum Zitat 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):5512–5528CrossRefPubMed 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):5512–5528CrossRefPubMed
19.
Zurück zum Zitat 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 CrossRefPubMed 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 CrossRefPubMed
20.
Zurück zum Zitat 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):427–432PubMed 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):427–432PubMed
22.
Zurück zum Zitat 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):837–845CrossRefPubMed 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):837–845CrossRefPubMed
23.
Zurück zum Zitat 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):1004–1014CrossRefPubMed 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):1004–1014CrossRefPubMed
24.
Zurück zum Zitat 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):736–741CrossRefPubMed 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):736–741CrossRefPubMed
25.
Zurück zum Zitat 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 CrossRefPubMed 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​ CrossRefPubMed
26.
Zurück zum Zitat 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):781–786CrossRefPubMed 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):781–786CrossRefPubMed
27.
Zurück zum Zitat 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):11–18PubMed 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):11–18PubMed
31.
Zurück zum Zitat 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 CrossRef 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 CrossRef
32.
Zurück zum Zitat 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 PubMedCentralPubMed 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 PubMedCentralPubMed
Metadaten
Titel
Activated CD8+ T Cells and NKT Cells in BAL Fluid Improve Diagnostic Accuracy in Sarcoidosis
verfasst von
A. Tøndell
A. D. Rø
A. Åsberg
M. Børset
T. Moen
M. Sue-Chu
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Lung / Ausgabe 1/2014
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-013-9527-8

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