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Mohammad, Imran, 2012. Studies on the role of alpha enolase as a candidate autoantigen in pristane-induced arthritis and immunological tolerance of citrullinated type II collagen. Second cycle, A1N, A1F or AXX ( AXX). Uppsala: SLU, Dept. of Molecular Biosciences

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Abstract

Rheumatoid Arthritis is a symmetric polyarticular disease, which mainly targets the
synovial membrane, cartilage and bone of small diarthrodial joints of hand and feet. The
etiology of rheumatoid arthritis remains uncertain. Pristane‐induced arthritis in the DA
rat is a widely used experimental arthritis model. The mechanisms involved in arthritis
development are not known. PIA is MHC class II associated and CD4+ T cells can transfer
the disease to naïve recipients. As in human RA the autoantigens driving the joint
inflammation are not yet known. In our lab, the immune responses against ubiquitously
expressed RNA binding protein hnRNP‐A2 (RA33), cartilage specific rat CII and CXI as
candidate autoantigens in PIA were studied. In the present study, we investigated the
immune responses to the tissue non‐specific antigen α‐enolase. In my thesis, the first
chapter shows the immune response against α‐enolase as autoantigen. The MHC
dependency and association was assessed in MHC congenics rats. The results obtained
will be useful to understand the T cell pathology in PIA and RA.
In the second chapter of my thesis we discuss immune tolerance towards a cartilage
specific autoantigen, mouse CII (mCII). The mCII expression in the thymus was studied.
From the obtained data two hypotheses of tolerance breakage can be drawn. According
to one hypothesis, the CII expressed in the thymus undergo post‐translational
modification and gets converted into citrullinated CII by the PAD enzymes. The
citrullinated CII undergo tolerization and the T cells in the periphery come into contact
with native CII in joints and recognize it as foreign. Therefore, the T cells invoke
autoimmune response against the native CII in joint. In another hypothesis, the T cells
get tolerized towards native CII expressed in thymus. The T cells in the periphery are
presented with neoepitopes in the joints, e.g. due to citrullination of CII in joints. This
condition elicits the immune response towards citrullinated CII in joints.

Main title:Studies on the role of alpha enolase as a candidate autoantigen in pristane-induced arthritis and immunological tolerance of citrullinated type II collagen
Authors:Mohammad, Imran
Supervisor:Haag, Sabrina and Raposo, Bruno and Tuncel, Jonatan and Linné, Tommy
Examiner:Fossum, Caroline
Series:UNSPECIFIED
Volume/Sequential designation:UNSPECIFIED
Year of Publication:2012
Level and depth descriptor:Second cycle, A1N, A1F or AXX
Student's programme affiliation:NM003 Biotechnology - Master's Programme 120 HEC
Department:(VH) > Dept. of Molecular Biosciences
Keywords:rheumatoid arthritis, collagen type II, enolase, IL-17, PADI2, PADI4
URN:NBN:urn:nbn:se:slu:epsilon-s-1867
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-s-1867
Subjects:Life sciences
Language:English
Deposited On:23 Nov 2012 11:52
Metadata Last Modified:22 Nov 2013 08:31

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