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Published ahead of print on January 26, 2006, doi:10.1164/rccm.200507-1126OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 10, May 2006, 1145-1154

A more recent version of this article appeared on May 15, 2006
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Submitted on July 21, 2005
Accepted on January 26, 2006

Protein Profiles of Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis

Eva Kriegova1, Christian Melle2, Vitezslav Kolek1, Beata Hutyrova1, Frantisek Mrazek1, Annett Bleul2, Roland M du Bois3, Ferdinand von Eggeling2, and Martin Petrek1*

1 Medical Faculty, Palacky University, Olomouc, Czech Republic, 2 CUCA, Institute of Human Genetics and Anthropology, Friedrich-Schiller-University, Jena, Germany, 3 Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom

* To whom correspondence should be addressed. E-mail: petrekm{at}fnol.cz.

Background: Pulmonary sarcoidosis is a multisystem granulomatous disease with varying clinical phenotypes. So far, there has been little information on protein patterns (PPs) of bronchoalveolar lavage fluid (BALF) from sarcoidosis patients and no data are available on PPs in clinical disease subtypes. Objectives: To investigate the PP of BALF from patients with pulmonary sarcoidosis (S), to evaluate if PPs reflect disease course as assessed by chest X-ray (CXR) and finally to compare PPs between patients with/without Lofgren's syndrome (LS). Methods: SELDI-TOF MS was applied to investigate PPs in unconcentrated BALF from 65 patients (CXR-stage I, n=32; CXR-stage II, n=22, CXR-stage III, n=11) and 23 healthy, control subjects (C). Mann-Whitney U-test was used to detect differentially expressed protein peaks. After reverse-phase fractionation, peptide fingerprint mapping and immunodepletion were used to identify deregulated (upregulated or downregulated) proteins. Results: Forty differentially expressed protein entities (2.75-185.62 kDa) were detected in S vs. C (p<0.05). While 13 peaks (33 %) were present across all CXR-stages, 27 (67 %) were specific for particular CXR-stages. Comparison of PPs between CXR-stage I patients with/without LS revealed 25 differentially expressed peaks. The total number of deregulated peaks and also of those associated with sarcoidosis as a whole was markedly lower in patients with LS in comparison with other sarcoid phenotypes. Human serum albumin, alpha1-antitrypsin and protocadherin-2 precursor were identified from "sarcoidosis associated" PP. Conclusion: SELDI-TOF MS enables determination of protein patterns in sarcoid BALF and allows detection of protein patterns linked to particular disease course.


Key words: Diffuse lung disease, Lofgren's syndrome, SELDI-TOF MS, proteomics, albumin, alpha1-antitrypsin, protocadherin-2




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