SAT0497 A PILOT PROTEOMIC ANALYSIS OF PLASMA BIOMARKERS IN IgA VASCULITIS
Authors: S. Demir, M. Sardan, I. Yet, E. Sag, Y. Bilginer, Ö. Celikbicak, S. Özen
Journal: Annals of the Rheumatic Diseases (2020)

Background: IgA vasculitis/ Henoch Schönlein Purpura (IgAV/HSP) is the most common vasculitis of childhood, characterized by the IgA1 immune deposits in the small vessels. Although it is very common, the understanding of its molecular pathogenesis is still very limited. Objectives: We aimed to analyse plasma proteomes of IgAV/HSP patients using nano liquid chromatography – tandem mass spectrometry (nLC-MS/MS) to investigate the disease pathogenesis. Methods: IgAV/HSP was diagnosed according to the Ankara criteria in 2008 (1). Five active IgAV/HSP patients and two age and gender-matched health controls were enrolled in this pilot study. Serum samples from subjects were collected on the same day of IgAV/HSP diagnosis and before steroid or other immunosuppressive treatment initiated. Sample preparation was carried out using PreOmics İST Kit. We investigated the alteration of serum proteome using the nano LC-MS/MS approach. Bruker raw files were analyzed using the proteomics software Max Quant (1.6.7.0). The human reference proteome set from UniProt was used to identify proteins. Proteomic data were analyzed with Perseus 1.6.7.0. Results: The data file includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ) values of each sample. 345 proteins were reported per sample. Identifications from the reverse decoy database, identified by site only and known contaminants were excluded. Data were log transformed. Two sample T-test was performed between groups. We identified 23 significantly different expressed proteins (Table 1). Mainly the differentially expressed proteins were in the Ig and complement pathway, innate immune inflammatory, and were among the structural cytoskeletal filaments. The levels of Complement C3, Apolipoprotein E, Glyceraldehyde-3-phosphate dehydrogenase, Filamin-A, Alpha-1B-glycoprotein, Tubulin beta-1 chain, Lipopolysaccharide-binding protein, Ig mu chain C region were significantly higher in IGAV patients. Table 1. List of differentially expressed proteins identified in IgAV compared to healthy controls Majority protein IDs Protein names Gene names p-value O75822 Eukaryotic translation initiation factor 3 subunit J EIF3J 0,004 P05106; H3BM21 Integrin beta-3 ITGB3 0,008 P02743 Serum amyloid P-component APCS 0,015 A0A0J9YX35 unknown 0,015 A2NJV5; A0A075B6S2 unknown IGKV A18; IGKV2D-29 0,021 P02679 Fibrinogen gamma chain FGG 0,022 A0A0C4DH36 unknown IGHV3-38 0,024 P0DP03; P01768 Ig heavy chain V-III region CAM 0,024 O14791 Apolipoprotein L1 APOL1 0,025 P01024 Complement C3 C3 0,030 P02675 Fibrinogen beta chain; Fibrinopeptide B FGB 0,030 P01860 Ig gamma-3 chain C region IGHG3 0,031 A0A075B7D8 unknown IGHV3OR15-7 0,034 P02649 Apolipoprotein E APOE 0,035 P04406 Glyceraldehyde-3-phosphate dehydrogenase GAPDH 0,037 A0A075B6R2; A0A087WW49 unknown IGHV4-4 0,039 P21333 Filamin-A FLNA 0,043 P04217 Alpha-1B-glycoprotein A1BG 0,045 P02790 Hemopexin HPX 0,046 A0A0C4DH25 unknown IGKV3D-20 0,047 Q9H4B7 Tubulin beta-1 chain TUBB1 0,049 P18428 Lipopolysaccharide-binding protein LBP 0,049 P01871 Ig mu chain C region IGHM 0,050 Conclusion: This pilot proteomic study may provide us a perspective in the pathogenesis of IgAV (HSP). References: [1]Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 2010;69(5):798e806. Disclosure of Interests: Selcan Demir: None declared, Melis Sardan: None declared, Idil Yet: None declared, Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ömür Celikbicak: None declared, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis