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Transglutaminase and peptidylarginine deiminase in the pathogenesis of autoimmune diseases

Roth, Bodil LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:9.
Abstract
Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune

disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific glutamine residues of

gliadins have been identified. A similar situation is seen in rheumatoid arthritis with both anticitrullinated

protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme,

peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an

enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. However,

this hypothesis is challenged by findings in cases of primary Sjögren’s syndrome (pSS), who do

not express ACPA, but who... (More)
Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune

disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific glutamine residues of

gliadins have been identified. A similar situation is seen in rheumatoid arthritis with both anticitrullinated

protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme,

peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an

enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. However,

this hypothesis is challenged by findings in cases of primary Sjögren’s syndrome (pSS), who do

not express ACPA, but who have been reported to carry anti-PAD. Objectives: Reproducing the

study claiming the presence of anti-PAD in pSS. Screening for ACPA and antibodies against

TG2 and PAD in pSS (n=78), multiple sclerosis (MS) (n=85), and Alzheimer’s disease (AD)

(n=79). Methods: ELISAs. Results: With blood donors (n=100) as controls, no increased

prevalence of autoantibodies was found among the patient groups tested. Conclusions: Contrary

to what has been published previously, patients with pSS do not express anti-PAD. The

hypothesis of a complex between an enzyme and its modified substrate constituting the

neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2, and

ACPA is comparatively restricted. Although attractive from a theoretical point of view, PAD and

TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. Venge, Per, Institutionen för medicinska vetenskaper, Akademiska sjukhuset, 75185 Uppsala
organization
publishing date
type
Thesis
publication status
published
subject
keywords
multiple sclerosis, pathogenesis, peptidylarginine deiminase, transglutaminase., Sjögren’s syndrome, autoimmune, Alzheimer’s disease
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:9
pages
100 pages
publisher
Chronic Inflammatory and Degenerative Diseases Research Unit
defense location
Universiteteklinikernas Aula, ingång 35, Universitetssjukhuset MAS, Malmö
defense date
2008-02-15 09:15
ISSN
1652-8220
ISBN
978-91-85897-62-9
language
English
LU publication?
yes
id
1fb5b4b6-837b-406f-bd28-8ab80d8fd6fc (old id 950086)
date added to LUP
2008-01-24 11:27:42
date last changed
2016-09-19 08:44:50
@phdthesis{1fb5b4b6-837b-406f-bd28-8ab80d8fd6fc,
  abstract     = {Coeliac disease (CD) is becoming a model for understanding the pathogenesis of autoimmune<br/><br>
disorders. In CD, antibodies against transglutaminase 2 (TG2) and specific glutamine residues of<br/><br>
gliadins have been identified. A similar situation is seen in rheumatoid arthritis with both anticitrullinated<br/><br>
protein antibodies (ACPA) and auto-antibodies against the citrullinating enzyme,<br/><br>
peptidylarginine deiminase (PAD). Previously, we have suggested that a complex between an<br/><br>
enzyme and its modified substrate constitutes the neoantigen in autoimmune diseases. However,<br/><br>
this hypothesis is challenged by findings in cases of primary Sjögren’s syndrome (pSS), who do<br/><br>
not express ACPA, but who have been reported to carry anti-PAD. Objectives: Reproducing the<br/><br>
study claiming the presence of anti-PAD in pSS. Screening for ACPA and antibodies against<br/><br>
TG2 and PAD in pSS (n=78), multiple sclerosis (MS) (n=85), and Alzheimer’s disease (AD)<br/><br>
(n=79). Methods: ELISAs. Results: With blood donors (n=100) as controls, no increased<br/><br>
prevalence of autoantibodies was found among the patient groups tested. Conclusions: Contrary<br/><br>
to what has been published previously, patients with pSS do not express anti-PAD. The<br/><br>
hypothesis of a complex between an enzyme and its modified substrate constituting the<br/><br>
neoantigen in autoimmune diseases is still valid. The prevalence of anti-PAD, anti-TG2, and<br/><br>
ACPA is comparatively restricted. Although attractive from a theoretical point of view, PAD and<br/><br>
TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD.},
  author       = {Roth, Bodil},
  isbn         = {978-91-85897-62-9},
  issn         = {1652-8220},
  keyword      = {multiple sclerosis,pathogenesis,peptidylarginine
deiminase,transglutaminase.,Sjögren’s syndrome,autoimmune,Alzheimer’s disease},
  language     = {eng},
  pages        = {100},
  publisher    = {Chronic Inflammatory and Degenerative Diseases Research Unit},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Transglutaminase and peptidylarginine deiminase in the pathogenesis of autoimmune diseases},
  volume       = {2008:9},
  year         = {2008},
}