BETA THYMOSINS IN SCLERODERMA INTERSTITIAL LUNG DISEASE: BIOMARKERS OF ALVEOLITIS

Background: β-thymosins (Tβ) are a family of ubiquitous peptides mainly involved in sequestering G-actin and in the regulation of the cytoskeleton. They also have broad extra-cellular effects, such as the modulation of angiogenesis, inflammation and wound healing. In the extra-cellular compartment, as in platelet cloths or in biological fluid as tears and saliva, they have a paracrine effect. While Tβ4, the most abundant species, is constitutively expressed by all cell types, Tβ10 has been found to be produced in pre-cancer or cancer and by activated lymphocytes and can inhibit Tβ4 effects. Tβ4 sulfoxide (sTβ4), the product of oxidation of Tβ4, can be produced during the inflammatory process. The presence and the role of Tβ in bronchoalveolar lavage fluid (BALF) have never been investigated. Objectives: The aim of the study was to evaluate the presence of Tβ4, Tβ10 and sTβ4 in BALF of systemic sclerosis (SSc) patients with interstitial lung disease (ILD) compared to normal subjects and in relation to functional, radiological and biological lung parameters. Methods: Tβ4, sTβ4 and Tβ10 were studied in 46 SSc patients (mean age 55.9±14.9 years, median disease duration 4 years, 22% males, 33% diffuse diseases, 7% smokers) with evidence of ILD on high resolution computed tomography (HRCT) and in 15 normal subjects (mean age 60.0±12.0 years, 30% males, 20% smokers) using mass-spectrometry (RP-HPLC-ESI-IT-MS). Pulmonary function tests (PFTs) and HRCT were repeated after 12-month follow-up. Results: Tβ4, sTβ4 and Tβ10 BALF levels were higher in SSc patients than in controls and in the SSc patients with alveolitis than in the patients without alveolitis, even if the differences were not statistically significant. Higher Tβ4 levels were significantly associated to higher BALF macrophage count (r=0.37, p=0.026), while lower Tβ4 BALF levels were significantly associated to the worsening in the alveolar score (p=0.039). Higher sTβ4 BALF levels were associated to an higher BALF neutrophil percentage count (r=0.37, p=0.012) and BALF sTβ4/Tβ4 ratio was higher in the patients with alveolitis than in patients without (0.13±0.18 vs 0.08±0.21; p=0.024). A strong correlation was found between Tβ10 and Tβ4 BALF levels (r=0.70, p≤0.0001); moreover, Tβ10 BALF levels were independently and significantly associated with BALF CD3 percentage count (r=0.32, p=0.036). Lower carbon monoxide diffusing capacity (DLCO) and lower forced vital capacity (FVC) values were associated to higher Tβ10 and to higher sTβ4/Tβ4 ratio BALF levels respectively (r= -0.38, p= 0.009; r= -0.59, p= 0.027). Conclusion: Lower Tβ4 BALF levels were associated to a worsening of ground glass at one year follow-up. The presence of sTβ4 characterized the SSc patients with alveolitis as expected in such an inflammatory condition. Moreover, increased levels of Tβ10 and sTβ4 were found in patients with a worse lung functional impairment. Disclosure of Interest: none declaredCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 363Session: Cytokines and inflammatory mediators (Poster Presentations )