Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis--new pathways to epitope spreading. Clinical and experimental rheumatology. [Clin Exp Rheumatol] Journal article | | Title | Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis--new pathways to epitope spreading. | | Author(s) | Roth EB, Stenberg P, Book C, Sjöberg K | | Institution | Hospital Pharmacy, Malmö University Hospital, Malmö, Sweden. | | Source | Clin Exp Rheumatol 2006 Jan-Feb; 24(1):12-8. | | MeSH | Adult
Aged
Aged, 80 and over
Animals
Antirheumatic Agents
Arthritis, Rheumatoid
Autoantibodies
Citrulline
Epitopes
Female
Guinea Pigs
Humans
Hydrolases
Immunoglobulin A
Immunoglobulin G
Male
Methotrexate
Middle Aged
Recombinant Proteins
Transglutaminases
| | Abstract | OBJECTIVE: The findings of the involvement of tissue transglutaminase (tTg) in the pathogenesis of coeliac disease (CD) have stimulated progress in the field of auto-immune diseases. Another calcium-dependent cysteine enzyme, peptidylarginine deiminase type 4 (PAD4), seems to be involved in the pathogenesis of rheumatoid arthritis (RA). There are obvious similarities between Tgs and PADs.
METHODS: Using enzyme-linked immuno-sorbent assays, we have measured the occurrence of antibodies against guinea pig (gp) and human recombinant (hr) tTg, PAD and citrulline in 59 controls and 184 RA-patients, of whom 71 were treated with methotrexate (mtx).
RESULTS: In addition to the expected antibodies against citrulline (62%), sera from the 113 RA-patients without mtx treatment contained significantly increased frequencies of IgG anti-PAD (35%), IgA anti-gp-tTg (34%), IgA anti-hr tTg (20%), IgG anti-gp-tTg (13%) and IgA anti-hr-FXIII (15%) compared to controls. In sera from the mtx-treated RA-patients the expression of antibodies was reduced. In patients not treated with methotrexate there was a statistically significant correlation between, on one hand, IgG anti-PAD and on the other hand, IgG anti-citrulline, IgA anti-gp-tTg, IgA anti-hr-tTg, IgG anti-gp-tTg, IgG anti-hr-tTg, or IgA anti-hr-FXIII. In the mtx-treated group these correlations were less pronounced.
CONCLUSION: In addition to the expected antibodies against citrulline, sera from RA-patients contained antibodies against PAD and against Tgs of at least two kinds, indicating that the specificity for anti-tTg in CD is far from complete. Most of the patients displayed more than one antibody, a possible indication of epitope spreading. MTX-treatment reduced the expression of antibodies. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16539813 |
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