Transglutaminase and peptidylarginine deiminase in the pathogenesis of autoimmune diseases
(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:
https://lup.lub.lu.se/record/950086
- author
- Roth, Bodil LU
- supervisor
-
- Klas Sjöberg LU
- Pål Stenberg LU
- opponent
-
- Prof. Venge, Per, Institutionen för medicinska vetenskaper, Akademiska sjukhuset, 75185 Uppsala
- organization
- publishing date
- 2008
- type
- Thesis
- publication status
- published
- subject
- keywords
- multiple sclerosis, pathogenesis, peptidylargininedeiminase, 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 09:15:00
- 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
- 2016-04-01 14:44:24
- date last changed
- 2019-05-21 22:22:42
@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}}, keywords = {{multiple sclerosis; pathogenesis; peptidylargininedeiminase; transglutaminase.; Sjögren’s syndrome; autoimmune; Alzheimer’s disease}}, language = {{eng}}, 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}}, url = {{https://lup.lub.lu.se/search/files/4135860/1027082.pdf}}, volume = {{2008:9}}, year = {{2008}}, }