SAT0497 A PILOT PROTEOMIC ANALYSIS OF PLASMA BIOMARKERS IN IgA VASCULITIS

• Published in: Annals of the rheumatic diseases Vol. 79; no. Suppl 1; pp. 1204 - 1205
• Main Authors: Demir, S., Sardan, M., Yet, I., Sag, E., Bilginer, Y., Celikbicak, Ö., Özen, S.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2020
• Subjects: Amino acid sequence; Amyloid; Apolipoprotein E; Apolipoproteins; Arteritis; Children; Complement component C3; Contaminants; Cytoskeleton; Dehydrogenases; Fibrinogen; Filaments; Glyceraldehyde-3-phosphate dehydrogenase; Glycoproteins; Granulomatosis; Hemopexin; Immunoglobulin A; Inflammation; Initiation factor eIF-3; Lipopolysaccharide-binding protein; Lipopolysaccharides; Liquid chromatography; Mass spectroscopy; Pathogenesis; Proteins; Proteomes; Proteomics; Purpura; Schonlein-Henoch purpura; Takayasu's disease; Tubulin; Vasculitis; Ankara Turkey; Turkey
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2020-eular.6230

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 controlsMajority protein IDsProtein namesGene namesp-valueO75822Eukaryotic translation initiation factor 3 subunit JEIF3J0,004P05106;H3BM21Integrin beta-3ITGB30,008P02743Serum amyloid P-componentAPCS0,015A0A0J9YX35unknown0,015A2NJV5;A0A075B6S2unknownIGKV A18;IGKV2D-290,021P02679Fibrinogen gamma chainFGG0,022A0A0C4DH36unknownIGHV3-380,024P0DP03;P01768Ig heavy chain V-III region CAM0,024O14791Apolipoprotein L1APOL10,025P01024Complement C3C30,030P02675Fibrinogen beta chain; Fibrinopeptide BFGB0,030P01860Ig gamma-3 chain C regionIGHG30,031A0A075B7D8unknownIGHV3OR15-70,034P02649Apolipoprotein EAPOE0,035P04406Glyceraldehyde-3-phosphate dehydrogenaseGAPDH0,037A0A075B6R2;A0A087WW49unknownIGHV4-40,039P21333Filamin-AFLNA0,043P04217Alpha-1B-glycoproteinA1BG0,045P02790HemopexinHPX0,046A0A0C4DH25unknownIGKV3D-200,047Q9H4B7Tubulin beta-1 chainTUBB10,049P18428Lipopolysaccharide-binding proteinLBP0,049P01871Ig mu chain C regionIGHM0,050Conclusion: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