The antigen specificity of the rheumatoid arthritis-associated ACPA directed to citrullinated fibrin is very closely restricted

Iobagiu, Cristina; Magyar, Anna; Nogueira, Léonor; Cornillet, Martin; Sebbag, Mireille; Arnaud, Jacques; Hudecz, Ferenc; Serre, Guy

doi:10.1016/j.jaut.2011.07.003

Cited by 45 publications

(35 citation statements)

References 36 publications

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“…In the present work, we have analysed the relationship between the autoantibodies directed against two peptides, α36–50Cit 38,42 and β60–74Cit 60,72,74 , previously identified as containing the immunodominant epitopes of citrullinated fibrin18 19 with AhFibA and anti-CCP2 antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…We identified two peptides, α36–50Cit 38,42 and β60–74Cit 60,72,74 , derived from the α-chains and β-chains of fibrin respectively, as bearing the immunodominant epitopes. A large majority of AhFibA-positive sera were either only reactive to α36–50Cit 38,42 (α-sera) or only to β60–74Cit 60,72,74 (β-sera) or to both these peptides (αβ-sera) 18 19. Then, we refined the epitope mapping and identified two 4 amino acids (aa) or 5-aa-long sequences that defined two epitopes (α′- and α-epitope) on α36–50Cit 38,42 and one 5-aa β-epitope on β60–74Cit 60,72,74 19.…”

Section: Introductionmentioning

confidence: 99%

“…A large majority of AhFibA-positive sera were either only reactive to α36–50Cit 38,42 (α-sera) or only to β60–74Cit 60,72,74 (β-sera) or to both these peptides (αβ-sera) 18 19. Then, we refined the epitope mapping and identified two 4 amino acids (aa) or 5-aa-long sequences that defined two epitopes (α′- and α-epitope) on α36–50Cit 38,42 and one 5-aa β-epitope on β60–74Cit 60,72,74 19. By analysing individual sera, we found that a large majority of α-sera recognised only the α-epitope, and that β-sera recognised only the β-epitope, whereas αβ-sera had a less restricted profile recognising the α′-epitope in addition to the α- and β-epitopes.…”

Section: Introductionmentioning

confidence: 99%

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The fibrin-derived citrullinated peptide β60–74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies

Cornillet¹,

Sebbag²,

Verrouil

et al. 2014

Annals of the Rheumatic Diseases

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The fibrin-derived citrullinated peptide β60–74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies

Cornillet¹,

Sebbag²,

Verrouil

et al. 2014

Annals of the Rheumatic Diseases

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“…Cit-ME (peptide sequence scheme is demonstrated in Fig. 1A), matched non-citrullinated peptide containing arginine or lysine instead of citrulline (Non-Cit-ME), citrullinated b-fibrinogen peptide (b-Fib-Cit) (21), and the matched non-citrullinated b-fibrinogen peptide containing arginine instead of citrulline (b-Fib-NC) were used. The multiepitope synthetic peptides were obtained from GL Biochem (Shanghai, China).…”

Section: Induction Of Aia and Peptide Treatment Regimenmentioning

confidence: 99%

Immune Tolerance Induction with Multiepitope Peptide Derived from Citrullinated Autoantigens Attenuates Arthritis Manifestations in Adjuvant Arthritis Rats

Gertel

Serre

Shoenfeld

et al. 2015

The Journal of Immunology

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Citrullinated peptides are major targets of disease-specific autoantibodies in rheumatoid arthritis. Currently, citrullinated peptides are used as biomarkers for diagnosing rheumatoid arthritis by measuring anti-citrullinated protein Ab (ACPA) titers in patients’ sera. The accumulation of citrullinated proteins at synovial inflammation sites suggests that they are possible targets for tolerance induction. The objective of the present study was to determine whether citrullinated peptides could induce tolerance in an experimental arthritis model in rats. In view of the multiplicity of target citrullinated autoantigens described for ACPA, we generated a multiepitope citrullinated peptide (Cit-ME), derived from major prevalent citrullinated autoantigens (citrullinated filaggrin, fibrinogen, vimentin, and collagen type II), and studied its effects on arthritic rats. Adjuvant-induced arthritis was induced in Lewis rats. Beginning at day 7 after disease induction, the rats received eight s.c. injections of Cit-ME on alternate days. Differences in clinical status and modulation of T cell populations were analyzed. In adjuvant-induced arthritis rats treated with Cit-ME, disease severity was significantly reduced compared with that of untreated rats. Moreover, amelioration of disease manifestations was related to an increased regulatory T cell subset and an elevated apoptosis rate of T cells associated with reduced Th17 cells. Thus, the use of citrullinated peptides–based immunotherapy may be a promising approach for tolerance induction in experimental arthritis and perhaps even in susceptible individuals that are ACPA-seropositive in human arthritis.

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“…SSc [115][116][117] and rheumatoid arthritis (RA) [118,119] represent conditions in which environmental factors have different weights [120,121], as well illustrated by the significantly different concordance rates in monozygotic twins which are below 5% and lower compared to dizygotic twins [31] and approximately 15%, respectively (Table 1). For these reasons, one would expect different roles of epigenetic changes as well but data from disease-specific fibroblasts share some common features [120,122].…”

Section: From Geoepidemiology To Pollution In Slementioning

confidence: 99%

The Therapeutic Potential of Epigenetics in Autoimmune Diseases

Santis

Selmi

2011

Clinic Rev Allerg Immunol

109

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A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases.

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The antigen specificity of the rheumatoid arthritis-associated ACPA directed to citrullinated fibrin is very closely restricted

Cited by 45 publications

References 36 publications

The fibrin-derived citrullinated peptide β60–74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies

The fibrin-derived citrullinated peptide β60–74Cit60,72,74 bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies

Immune Tolerance Induction with Multiepitope Peptide Derived from Citrullinated Autoantigens Attenuates Arthritis Manifestations in Adjuvant Arthritis Rats

The Therapeutic Potential of Epigenetics in Autoimmune Diseases

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