PhD Scientific Days 2017

Oral Presentations: Basic Sciences II.

Analysis of linear antibody epitopes on factor H and CFHR1 using sera of patients with autoimmune atypical hemolytic uremic syndrome

Előadó neve

Dr. Trojnár, Eszter

Előadó munkahelye

III. Department of Internal Medicine, Research Laboratory

Előadó telefonszáma

0630/6510139

Előadó e-mail címe

eszter.trojnar@gmail.com

Az előadás címe

Analysis of linear antibody epitopes on factor H and CFHR1 using sera of patients with autoimmune atypical hemolytic uremic syndrome

Szerző(k) neve és munkahelye

Eszter Trojnár1, Mihály Józsi2, Katalin Uray3, T Sakari Jokiranta4, Zoltán Prohászka5
1 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary
2 MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary
3 MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary
4 Research Programs Unit, Immunobiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
5 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary

Témacsoport

molecular sciences

Szekció

Oral Presentations: Basic Sciences II.

Data of the presenter

Doctoral School: Basic Medicine
Program: Clinical and Experimental Cardiology / Atherosclerosis
Supervisor: Zoltán Prohászka
Email address of the presenter: eszter.trojnar@gmail.com

Text of the abstract

Analysis of linear antibody epitopes on factor H and CFHR1 using sera of patients with autoimmune atypical hemolytic uremic syndrome

Introduction: In autoimmune atypical hemolytic uremic syndrome (aHUS) the complement regulator factor H (FH) is blocked by anti-FH autoantibodies, while 90% of the patients carry a homozygous deletion of its homologue protein, CFHR1.
Aims: Since the molecular basis of autoantibody binding in disease pathogenesis is unknown, we performed epitope mapping of FH to provide structural insight in the autoantibody recruitment on FH and potentially CFHR1.
Methods: With overlapping synthetic peptides we located the amino acids (aa) involved in binding of acute and convalescence stage autoantibodies in eight autoimmune aHUS patients. We confirmed the location of the mapped epitopes using recombinant FH domains 19-20 that carried single-aa substitutions at the suspected antibody binding sites in three of our patients. Location of the linear epitopes and the introduced point mutations was visualized using crystal structures of the corresponding domains of FH and CFHR1.
Results: We identified three linear epitopes on FH (aa1157-1171; aa1177-1191; aa1207-1226) and one on CFHR1 (aa276-290) that are recognized both in the acute and convalescence stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite 7 of our patients being deficient for CFHR1. Epitope mapping with the domain constructs validated the location of the linear epitopes on FH with a distinct autoantibody binding motif within aa1183-1198 in line with published observations.
Summary: The linear epitopes we identified contain amino acids involved in C3b and sialic acid binding on FH, which may explain the functional deficiency of FH in the presence of autoantibodies. Our data identifies the exact structures involved in autoantibody recruitment on FH and confirms the presence of an autoantibody binding epitope on CFHR1.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1037

Authors (legacy)

Eszter Trojnár1, Mihály Józsi2, Katalin Uray3, T Sakari Jokiranta4, Zoltán Prohászka5
1 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary
2 MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary
3 MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary
4 Research Programs Unit, Immunobiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
5 3rd Dept. of Internal Medicine, Research Laboratory, Semmelweis University, Budapest, Hungary