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The Autoimmune Repertoire in Idiopathic Pulmonary Fibrosis
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A1063 - The Autoimmune Repertoire in Idiopathic Pulmonary Fibrosis
Author Block: E. Wiklundh1, C. Hellstrom2, C. H. Van Moorsel3, J. C. Grutters4, P. Nilsson2, B. Crestani5; 1Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 2Affinity Proteomics, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden, 3St Antonius Hospital Pulmonology, Nieuwegein, Netherlands, 4Dept of Pulmonology, St Antonius Hosp, Nieuwegein 3435 CM, Netherlands, 5Service de Pneumologie, Hopital Bichat, Paris, France.
Background: Idiopathic pulmonary fibrosis (IPF) belongs to the group of interstitial pneumonias; it is a chronic disease characterized by a continuous development of pulmonary fibrosis. IPF is progressive and primarily affects older adults, and leads to a steady decline in lung function causing severe impairment of quality of life and, usually, fatal outcomes for those affected. Autoimmunity has previously been investigated in IPF, but the pathogenic role has not been determined.
Materials and Methods: A set of 175 targets from 129 proteins were selected for suspension bead array, 253 serum samples and 99 paired bronchoalveolar lavage (BAL) samples from IPF patients were run together with 22 unpaired IPF BAL samples and 72 BAL samples from sarcoidosis (non-lofgren syndrome, nLS and lofgren syndrome, LS), asthma and healthy controls. A verification assay was performed using an additional 81 serum samples from sarcoidosis and healthy controls, against 78 selected autoantigen candidates from the first assay. Furthermore, an epitope assay towards the protein fragment with highest reactivity frequency was conducted.
Results: In the first assay results showed 30 IgG targets with elevated reactivity levels against self-proteins. Overall, autorectivity was found in both BAL and serum, however results did not always match. Reactivity toward collagen 5A1 (COL5A1) was discovered with a statistical significant higher frequency in patients with IPF compared to all other groups apart from nLS, these results were found in both serum and BAL. In general, IPF and nLS displayed higher levels and frequencies of autoreactivity compared to all other diseases and controls, both in BAL and in serum. The target sequence from zinc finger 688 (ZNF688) exhibited similar autoreactivity levels as COL5A1, although ZNF had higher reactivities in patients with LS than COL5A1. The subsequent epitope assay done on COL5A1 revealed several epitopes, i.e. potential antigen sites, within a 51-amino acid region.
Conclusions: Autoantigens were found in the majority of patient samples, although there was a high interindividual variation, autoreactivity was also present in healthy subjects. Altogether, autoreactivity was higher in IPF and in nLS patients, both groups represent a higher fibrosis rate than the other diseases potentially linking autoreactivity to fibrosis development. The epitope of COL5A1 is proposed as an autoimmune target and of interest for further validation.
Author Block: E. Wiklundh1, C. Hellstrom2, C. H. Van Moorsel3, J. C. Grutters4, P. Nilsson2, B. Crestani5; 1Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 2Affinity Proteomics, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden, 3St Antonius Hospital Pulmonology, Nieuwegein, Netherlands, 4Dept of Pulmonology, St Antonius Hosp, Nieuwegein 3435 CM, Netherlands, 5Service de Pneumologie, Hopital Bichat, Paris, France.
Background: Idiopathic pulmonary fibrosis (IPF) belongs to the group of interstitial pneumonias; it is a chronic disease characterized by a continuous development of pulmonary fibrosis. IPF is progressive and primarily affects older adults, and leads to a steady decline in lung function causing severe impairment of quality of life and, usually, fatal outcomes for those affected. Autoimmunity has previously been investigated in IPF, but the pathogenic role has not been determined.
Materials and Methods: A set of 175 targets from 129 proteins were selected for suspension bead array, 253 serum samples and 99 paired bronchoalveolar lavage (BAL) samples from IPF patients were run together with 22 unpaired IPF BAL samples and 72 BAL samples from sarcoidosis (non-lofgren syndrome, nLS and lofgren syndrome, LS), asthma and healthy controls. A verification assay was performed using an additional 81 serum samples from sarcoidosis and healthy controls, against 78 selected autoantigen candidates from the first assay. Furthermore, an epitope assay towards the protein fragment with highest reactivity frequency was conducted.
Results: In the first assay results showed 30 IgG targets with elevated reactivity levels against self-proteins. Overall, autorectivity was found in both BAL and serum, however results did not always match. Reactivity toward collagen 5A1 (COL5A1) was discovered with a statistical significant higher frequency in patients with IPF compared to all other groups apart from nLS, these results were found in both serum and BAL. In general, IPF and nLS displayed higher levels and frequencies of autoreactivity compared to all other diseases and controls, both in BAL and in serum. The target sequence from zinc finger 688 (ZNF688) exhibited similar autoreactivity levels as COL5A1, although ZNF had higher reactivities in patients with LS than COL5A1. The subsequent epitope assay done on COL5A1 revealed several epitopes, i.e. potential antigen sites, within a 51-amino acid region.
Conclusions: Autoantigens were found in the majority of patient samples, although there was a high interindividual variation, autoreactivity was also present in healthy subjects. Altogether, autoreactivity was higher in IPF and in nLS patients, both groups represent a higher fibrosis rate than the other diseases potentially linking autoreactivity to fibrosis development. The epitope of COL5A1 is proposed as an autoimmune target and of interest for further validation.
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