Background/Purpose:

Antibodies recognizing cyclic citrullinated peptides (CCP) are highly specific for rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (poly JIA), and may both predict and contribute to early onset and an aggressive disease course. Risk factors for RA, including the HLA-DRB1 shared epitope (SE) and smoking, are associated with higher levels of anti-CCP antibodies. It is unknown what the natural targets of anti-CCP are, or how they are generated.  P. gingivalis, associated with gingivitis and periodontitis, expresses a citrullinated protein, α-enolase, with homology to human α-enolase, and thus is a strong candidate for the autoantigen bound by anti-CCP antibodies.  The P. gingivalis α-enolase may serve as a link between oral inflammation induced by P. gingivalis and arthritis. The pathogenesis of JIA may thus involve molecular mimicry between epitopes from citrullinated bacterial and human, triggering autoimmunity in genetically susceptible individuals.

Methods:

Anti-citrullinated enolase peptide antibodies (anti-CEP) were quantified by ELISA in plasma from 20 RF+ poly JIA patients ages 7.1-18.5 years and 20 age- and sex-matched controls. Target peptides were selected based on previously identified immunodominant epitopes in adult RA patients, and included P. gingivalis CEP citrulline- versus arginine-containing sequences and the human CEP peptide homologs. Citrullinated vimentin and citrullinated non-immunogenic CEP were negative controls.  Antibodies to CCP were assayed by QUANTA Lite CCP3.1 IgG/IgA ELISA.

Results:

Antibodies to CCP were detected in all 20 RF+ JIA patients and in one of 20 controls, though at low titer.   Antibodies to Hu-CEP were detected in 9 JIA patients (45%). All patients with anti-Hu-CEP antibodies also carried Abs to PG-CEP.  A tight correlation was found between anti-PG CEP and anti-Hu CEP (R²=0.70), suggesting cross-reactivity between antibodies.  Patients with the DRB1 shared epitope (n=12) were no more likely to carry anti-Hu-CEP (50%) or anti-PG-CEP (58%) than those without the shared epitope (n=8, 38%, 50%).  No differences were found between patients and controls in control peptide responses, which were all low.  Only weak correlations were detected between anti-CEP and age of onset or disease activity as assessed by ESR, CRP, active joint count, loss of range of motion, MD assessment or CHAQ. 

Conclusion:

A high proportion of patients with RF+ poly JIA develop Abs to citrillinated proteins, which were not detected in healthy children.  The coincidental occurrence of anti-Hu-CEP and anti-PG CEP suggest an etiologic role for P. gingivalis infection in poly JIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-response-to-porphyromonas-gingivalis-citrullinated-%ce%b1-enolase-cross-reacts-with-human-%ce%b1-enolase-in-polyarticular-jia-patients/