Heat shock proteins as 'danger signals' in sarcoidosis A. Dubaniewicz (Gdansk, Poland)
Source: International Congress 2014 – ILDs 6
Session: ILDs 6 Session type: Thematic Poster Session Number: 3790
Disease area: Interstitial lung diseases, Respiratory infectionsAbstract Sarcoidosis (SA) is a multisystem granulomatous disease with unknown etiology. Like other autoimmunological disorders, SA develops due to a combination of genetic and non-infectious/infectious factors.We evidenced, that the same mycobacterial heat shock proteins (Mtb-HSPs, especially HSP16, the main marker of dormant stage of (myco)bacteria), occurring in sarcoid tissues and in precipitated immune complexes (CIs), were inducing immune response dependently on different genetic background of host (HLA and non-HLA-NRAMP1,FCGRIIA,IIC,IIIA ), developing acute sarcoidosis/Löfgren syndrome, chronic SA, latent, or active TB. In the same group of SA and TB patients, we also found increased monocytes phagocytic activity, but in contrast to TB, decreased clearance of antigens/CIs by resistant to apoptosis CD14+Fcg RII+Fcg RIII+CR1-CR4- monocytes with their decreased production of microbicidal/degradable nitric oxide and glutation, were detected in sarcoidosis.All these results may explain increased uptake of low-degradable microbial and non-infectious antigens by the same polymorphic pattern recognition receptors on genetically altered APC with following persistent 'danger signals' load: microbial HSP (pathogen-associated molecular patterns-PAMPs and/or tissue damage-associated molecular patterns-DAMPs) and human HSPs (endogenous DAMPs) with their decreased clearance, antigenemia/immunocomplexemia, increased presentation to T-cells in the context of particular HLA and B-cells, bystander activation, cross-reactivity, decreased co-stimulatory molecules and regulatory T-cells expression, apoptosis, and oxidative stress, resulting in exaggerated lymphoproliferation and sarcoid granuloma formation. Funding:grant 5160/B/P01/2010/39.Rating:
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A. Dubaniewicz (Gdansk, Poland). Heat shock proteins as 'danger signals' in sarcoidosis. Eur Respir J 2014; 44: Suppl. 58, 3790
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