Biomarkers in sarcoidosis 4515 The role of vitamin D 3 in the local inflammatory process in sarcoidosis ( SA )

printing supported by . Visit Chiesi at Stand D.30 TUESDAY, SEPTEMBER 27TH 2011 in the degradation of chitin and chitin-like substrate, identified in a wide variety of organisms. Increased concentrations of chitotriosidase have been reported in several lysosomal storage diseases and more recently also in sarcoidosis. In this study chitotriosidase concentrations were evaluated in a population of 233 sarcoidosis patients and 70 controls in order to verify enzyme specificity and sensibility and to evaluate chitotriosidase prognostic meaning. Chitotriosidase has been found significantly increased in serum of patients with sarcoidosis than in controls (p< 0.0001). ROC curve analysis revealed: cut-off value of 39.50 nmol/h/ml, sensitivity 89,70% and specifity 90%. The analysis of chitotriosidase in different phenotypic subgroups of patients revealed very high serum enzyme levels in symptomatic patients requiring systemic steroid therapy at onset and after disease relapses. In conclusion as a new potential biomarker of sarcoidosis severity, chitotriosidase resulted sensitive, reproducible and easily detectable in serum. 4519 Mycobacterial heat shock protein 16 kDa, marker of dormant stage of mycobacteria, in precipitated circulating immune complexes in sarcoidosis Anna Dubaniewicz1, Adam Holownia2, Mahavir Singh4. 1Department of Pulmonology, Medical University of Gdansk, Gdank, Poland; 2Department of Clinical Pharmacology, Medical University of Bialystok, Bialystok, Poland; 3Department of Genome Analysis, Helmholtz Center for Infection Research and LIONEX Diagnostics & Therapeutics GmbH, Braunschweig, Germany M. tuberculosis antigens, e.g., heat shock proteins (Mtb-hsp), genetic factor and autoimmunity have been explored as potential causes of sarcoidosis (SA). Mtbhsp inducing both cellular and humoral immune response may provide a link between infection and autoimmunity. We have recently demonstrated the presence of Mtb-hsp70, Mtb-hsp65 and Mtb-hsp16 in sarcoid tissue. Higher occurrence of serum Mtb-hsp70 than Mtb-hsp65 and Mtb-hsp16 in SA patients could be caused by sequestration of Mtb-hsp65 and Mtb-hsp16 in circulating immune complexes (CIs). To test this hypothesis, we have evaluated and quantified Mtb-hsp70, Mtbhsp65 and Mtb-hsp16 in precipitated CIs from blood of 20 patients with SA, 19 patients with active tuberculosis (TB) and 21 healthy volunteers using PEG precipitation and Western Blot. The results showed significantly increased CIs levels in SA vs TB and Control, whereas there was no difference between TB and healthy individuals. The Mtb-hsp16, Mtb-hsp65 and Mtb-hsp70 concentrations in precipitated CIs were significantly higher in SA than in TB and Control, but there was no difference between TB and Control. In all tested groups, the Mtbhsp16 concentration was significantly increased than Mtb-hsp70 and Mtb-hsp65. In summary, our results show increased presence of Mtb-hsp16, Mtb-hsp65 and Mtb-hsp70 in precipitated CIs in sarcoidosis comparing to corresponding levels in TB and healthy individuals. It seems that Mtb-hsp16 may be more important than Mtb-hsp70 and Mtb-hsp65 in circulating immune complexes formation and possibly the protein may be implicated (auto)immune response in SA related to stationary-phase of M. tuberculosis. 4520 Use of discriminant analysis to assess pulmonary functional worsening in patients with sarcoidosis by means of a panel of inflammatory markers Gregorino Paone1,2 , Maria Rulli3 , Alessandro Belli3, Armanda Propati3 , Angelo Sbrocca3, Salvatore D’Antonio3, Alfredo Sebastiani3, Giovanni Puglisi3, Giovanni Galluccio3, Sandro Batzella3. 1Department of Cardiovascular, Respiratory and Morphologic Sciences, University “La Sapienza” S.Camillo-Forlanini Hospital, Rome, Italy; 2IRCCS Fondazione Don Carlo Gnocchi Onlus, Don Gnocchi, Milan, Italy; 3Department of Respiratory Diseases, S.Camillo-Forlanini Hospital, Rome, Italy Background: Sarcoidosis’ protean clinical course has prompted many studies to discover biomarkers which could help to trace disease progression and response to therapy. Aims: In our study we performed discriminant analysis, to investigate whether a panel of selected markers measured in BALF and serum from patients with sarcoidosis would help to predict pulmonary functional worsening. Methods: We enrolled in the study 30 consecutive individuals with sarcoidosis. At enrolment participants underwent pulmonary function tests, fiber-optic bronchoscopy and radiological evaluation. PFTs were also performed at follow-up visits during a 2 year period. Pulmonary function worsening was defined as a decline of TLC, FVC, FEV1> 15% and DLCO > 10%. BALF differential cell counts were performed in all participants and BAL and serum ECP, MPO, Tryptase, PIIIP and SIL2r concentrations were quantified by RIA and ELISA tests. Discriminant analysis was performed to optimize the accuracy of selected variables in predicting functional worsening. Results: Pulmonary function worsening was observed in 24% of participants. Applying discriminant analysis function a high classification rate was obtained.The following formula: CV= PMNBAL x 0.18 +ECPBAL x 1.20 -MPOBAL x 0.03 +TryptaseBAL x 1.21PIIIPBAL x0.1 -sIL2RBAL x0.01-1.183, allowed the correct allocation of 100% of participants. The positive likelihood ratio was >20 and the negative likelihood ratio was 0. Conclusions: Our results show that a panel of BAL markers may be used to distinguish patients with stable disease from individuals with pulmonary function worsening and may help to decide therapeutic strategies. 4521 Chronic fatigue in sarcoidosis-in-clinical-remission: Psychological and physical characteristics Ingrid Korenromp1,2 , Cobi Heijnen2, Oscar Vogels3, Jan Grutters1,4 . 1Department of Pulmonology, St. Antonius Hospital, Nieuwegein, Netherlands; 2Laboratory for Neuroimmunology and Developmental Origins of Disease, University Medical Center, Utrecht, Netherlands; 3Department of Neurology, St. Antonius Hospital, Nieuwegein, Netherlands; 4Division Heart & Lungs, University Medical Center, Utrecht, Netherlands When sarcoidosis is in clinical remission, complaints of chronic fatigue often persist. The exact features of this post-inflammatory fatigue are unknown. This study assesses the severity of fatigue and the presence of fatigue-related symptoms in sarcoidosis-in-clinical-remission. Furthermore, we evaluate psychological distress, pain and patient-reported sleep quality, and record physical activity levels and muscle strength as objective assessments of fatigue. Lastly, we assess the severity of fatigue at a follow-up. Methods: Seventy-five patients with sarcoidosis-in-clinical-remission were evaluated with the Checklist Individual Strength (fatigue), the SymptomChecklist-90 (psychological distress), the McGill Pain Questionnaire (pain), standardized interview (fatigue-related symptoms), sleep diary, accelerometer and muscle strength tests. Results: Fatigue severity mean score in sarcoidosis patients in-clinical-remission was high (fatigue-severity score: 30.5±15.5), and fatigue-related symptoms were significantly more present in the fatigued patients. Median time since diagnosis was 9 years. Fatigue was significantly associated with increased psychological distress, higher pain severity scores and more pain points, reduced physical activity and reduced muscle strength. Scores on sleep quality were normal. Response at followup was 87%. Fatigue severity scores of the responding group were significantly increased compared to a year before. Conclusions: Fatigue in sarcoidosis patients in clinical remission is a long-lasting and severe problem that deteriorates over time. This post-inflammatory chronic fatigue is associated with a constellation of psychological and physical symptoms. 825s Oral Presentation Room 3.2 14:45-16:45 Abstract printing supported by . Visit Chiesi at Stand D.30printing supported by . Visit Chiesi at Stand D.30