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P013 Porphyromonas gingivalis infection linked to ra onset and ANTI TNF alpha treatment non-response
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  1. M Jenning1,
  2. B Marklein1,
  3. Y Ytterberg2,
  4. A Catarina2,
  5. D Schaardenburg3,
  6. G Bürmester1,
  7. K Skriner1
  1. 1Department of Rheumatology and Clinical Immunology, Humboldt University and Free University, Berlin, Germany
  2. 2Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
  3. 3Amsterdam Rheumatology and Immunology Centre, Reade and Academic Medical Centre, Amsterdam, Netherlands

Abstract

Introduction Differences in enzymatic activity and pathogenic impact of Porphyromonas gingivalis (P.g.) peptidylarginine deiminase (PPAD) for development of RA have been published, confounded by different PPAD variations and methods used.

Objectives Enzymatic active PPAD isolated from an RA patient (RA-PPAD) was first time linked to citrullination of RA autoantigens, diagnosis, therapy response and RA-onset.

Methods Recombinant RA-PPAD cloned, verified by DNA sequencing and expressed in Escherichia coli and purified. RA-PPAD and its enzymatic activity was analysed using 2D-Elektrophoresis, mass spectrometry (MS), immunoblot and ELISA.

Results RA-PPAD autocitrullinates amino acid position 63 (aa63) and exhibits so far two new amino acid mutations aa73 F to L and aa447 E to V. Anti-citrullinated RA-PPAD antibodies were detected in 38% (n=36) of patients with RA, but were absent in Systemic lupus erythematosus (n=30), Osteoarthritis (n=36) and control sera (n=23). Twenty percent of RA patients (n=30) showed an increase in antibody-titre against citrullinated RA-PPAD after RA onset. High antibody titre against the cit-PPAD-peptide of 15aa (CPP) derived from the autocitrullination site (R63) correlates with TNFα-inhibitor (TBA) non-response (n=61). Anti-CPP levels correlate with DAS28,rheumatoid factor, α-CCP 2 levels and increase with age. RA-PPAD is able to citrullinate internal arginines in fibrinogen, vimentin, hnRNP-A2/B1 and histone H1. This internal citrullination-sites are recognised by RA sera and able to bind HLA401.

Conclusions Failure of P.g. clearance in RA patients may lead to excessive exposure of citrullinated self-antigens and bacterial antigens inducing immune-mimicry. P.g. infection can be linked to RA and its correlation to TBA non-response leads to the suggestion to clear P.g infection before α-TNF treatment.

Disclosure of interest None declared

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