Immunoglobulin G Subclass Profile of Anticitrullinated Peptide Antibodies Specific for Epstein Barr Virus-derived and Histone-derived Citrullinated Peptides

Panza, Filomena; Pratesi, Federico; Valoriani, Daniele; Migliorini, Paola

doi:10.3899/jrheum.130795

Cited by 7 publications

(8 citation statements)

References 10 publications

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“… (anti‐CCP), we confirmed that IgG4 anti‐CCP was almost as frequent (59%) as IgG1 (67%), whereas the occurrence rates of IgG2 (32%) and IgG3 (32%) anti‐CCP were considerably lower. Others have reported the presence of IgG1, IgG3 and IgG4 anti‐viral citrullinated peptide/histone citrullinated peptide in RA patients, while the presence of IgG2 anti‐viral citrullinated peptide/histone citrullinated peptide was negligible . The discrepancy between the present study and the study by Panza et al .…”

Section: Discussioncontrasting

confidence: 99%

“…As reported previously by Chapuy-Regaud et al [31] (anti-citrullinated fibrin antibodies) and Verpoort et al [29] (anti-CCP), we confirmed that IgG4 anti-CCP was almost as frequent (59%) as IgG1 (67%), whereas the occurrence rates of IgG2 (32%) and IgG3 (32%) anti-CCP were considerably lower. Others have reported the presence of IgG1, IgG3 and IgG4 anti-viral citrullinated peptide/histone citrullinated peptide in RA patients, while the presence of IgG2 anti-viral citrullinated peptide/histone citrullinated peptide was negligible [32]. The discrepancy between the present study and the study by Panza et al could be due to the use of different antigens in the antibody analyses, or that the patients were in different stages of the disease.…”

Section: Discussioncontrasting

confidence: 98%

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Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)

Martinsson

Johansson

Kastbom

2017

Clinical and Experimental Immunology

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Given the possible importance of anti-citrullinated peptide/protein antibodies (ACPA) for initiation and progression of rheumatoid arthritis (RA), extended knowledge about the different isotypes and subclasses is important. In the present study, we analysed the immunoglobulin (Ig)G subclasses regarding reactivity against cyclic citrullinated peptides (anti-CCP) among 504 clinically well-characterized patients with recent-onset RA in relation to smoking habits, shared epitope (SE) status and IgA and pan-IgG anti-CCP antibodies. All patients, regardless of pan-IgG anti-CCP status, were analysed for IgG1-4 CCP reactivity. Sixty-nine per cent were positive in any IgG anti-CCP subclass, and of these 67% tested positive regarding IgG1, 35% IgG2, 32% IgG3, and 59% IgG4 anti-CCP. Among ever-smokers the percentages of IgG2 anti-CCP (P = 0·01) and IgA anti-CCP (P = 0·002)-positive cases were significantly higher compared to never-smokers. A positive IgG anti-CCP subclass -negative cases. Combining SE and smoking data revealed that IgG1 and IgG4 anti-CCP were the IgG anti-CCP isotypes associated with expression of SE, although the lower number of patients positive for IgG2 or IgG3 anti-CCP could, however, have influenced the results. High levels of IgG2 anti-CCP were shown to correlate with expression of the 'non-SE' allele human leucocyte antigen (HLA)-DRB1*15. In conclusion, in this study we describe different risk factor characteristics across the IgG anti-CCP subclasses, where IgG2 appears similar to IgA anti-CCP regarding the predominant association with smoking, while IgG1 and IgG4 related more distinctly to the carriage of SE genes.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 98%

Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)

Martinsson

Johansson

Kastbom

2017

Clinical and Experimental Immunology

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“…Moreover, when the coexpression of different subclasses was analyzed, most sera were characterized by the contemporary presence of two or three subclasses when tested on VCP1, VCP2 and HCP2, while HCP1 often detected a single IgG subclass. 61 At variance with the above-mentioned studies, Verpoort et al 46 did not detect an increase in IgG4 ACPA. In fact, analyzing undifferentiated arthritis (UA) that may (UA !…”

Section: Subclasses Of Acpa Iggmentioning

confidence: 94%

Fingerprinting of anti-citrullinated protein antibodies (ACPA): specificity, isotypes and subclasses

Pratesi

Panza

Paolini

et al. 2015

Lupus

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Anti-citrullinated protein antibodies (ACPA) are a family of rheumatoid arthritis (RA)-specific autoantibodies that recognize the amino acid citrulline, resulting from the post-translational modification of arginine. Peptidyl arginine deiminase, the enzyme responsible for citrullination, is present in humans in different isoforms with different tissue distribution, enzymatic activity and target specificity; nonetheless, the number of proteins citrullinated in physiological or pathological conditions is wide, but not every citrullinated protein is a target for antibodies. In pre-RA patients the immune response to citrullinated antigens is initially restricted, expands with time and, after the onset of the disease, is relatively stable. ACPA are heterogeneous in terms of not only fine specificity but also isotype and IgG subclasses usage. This heterogeneity may be relevant for the immunopathogenesis of RA, conditioning the interaction of antibodies with complement and Fc receptors.

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“…2,3 Materials and methods Four hundred and forty-eight RA patients, followed in the Clinical Immunology Unit, University of Pisa, and in the Rheumatology Unit, University of Perugia, were recruited.…”

Section: Introductionmentioning

confidence: 99%

08.20 Acpa fingerprinting in established rheumatoid arthritis

Manca

Alunno

D'Amato

et al. 2017

Autoimmune Inflammation

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BackgroundAnti-citrullinated protein/peptide antibodies (ACPA) represent an important tool for the diagnosis of RA and the presence of multiple ACPA specificities is highly correlated with the evolution towards RA.1 However, a limited amount of information is available on the predictive value of single specificities on disease manifestations and response to therapy in established RAThe aim of the present work is to evaluate the diagnostic and prognostic value of the combined use of four well established citrullinated peptides as antigens for ACPA detection: VCP1 and VCP2 (derived from EBV proteins) and HCP1 and HCP2 (derived from histone H4).2,3 Materials and methodsFour hundred and forty-eight RA patients, followed in the Clinical Immunology Unit, University of Pisa, and in the Rheumatology Unit, University of Perugia, were recruited.RA patients were evaluated for systemic involvement, disease activity and severity, ongoing and past therapies.Anti-VCP1, -VCP2, -HCP1, -HCP2 were measured by home-made ELISA.Data were analysed by cluster analysis and principal component analysis.ResultsAntibodies to VCP1 were detected in 52% of RA patients; anti-VCP2 in 59,5%; anti-HCP1 in 57% and anti-HCP2 in 57,5%Cluster analysis and principal component analysis identify two subpopulations, that differ for ACPA levels, RF positivity, lung involvement and higher use of biological therapy.Patients were also subdivided in 5 groups according to the number of anti-peptide antibodies (negative for any, positive for one, for two, for three, for four). Mean antibody level and RF positivity progressively increased from the first to the last group, as well as the frequency of lung involvement.ConclusionsACPA are a family of antibodies with overlapping specificities. The results obtained with citrullinated peptides from EBV proteins and histone H4 suggest that fingerprinting of ACPA may be informative in established RA. A higher number of ACPA subtypes is predictive of lung involvement. Moreover, a broader ACPA repertoire also emerged as a feature of patients treated with biological therapy, thus probably affected by a more severe form of the disease.In conclusion, ACPA typing may be relevant for a better characterisation of some disease features in established RA.References1. Brink M, Hansson M, Mathsson L, et al. Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis. Arthritis Rheum. 2013;65(4):899–9102. Panza F, Pratesi F, Valoriani D, et al. Immunoglobulin G subclass profile of anticitrullinated peptide antibodies specific for Epstein Barr virus-derived and histone-derived citrullinated peptides. J Rheumatol2014;41(2): 407–8.3. Johansson L, Pratesi F, Brink M, et al. Antibodies directed against endogenous and exogenous citrullinated antigens pre-date the onset of rheumatoid arthritis. Arthritis Res Ther2016;18(1):127.

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Immunoglobulin G Subclass Profile of Anticitrullinated Peptide Antibodies Specific for Epstein Barr Virus-derived and Histone-derived Citrullinated Peptides

Cited by 7 publications

References 10 publications

Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)

Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)

Fingerprinting of anti-citrullinated protein antibodies (ACPA): specificity, isotypes and subclasses

08.20 Acpa fingerprinting in established rheumatoid arthritis

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