Anti-Cyclic Citrullinated Peptide Antibody Subclass Phenotypes in Polyarticular Juvenile Idiopathic Arthritis

Hannah Peckham¹, Lauren Bourke^2,3, Anna Radziszewska⁴, Maria Leandro⁵, Debajit Sen², Geraldine Cambridge⁶ and Yiannis Ioannou^7,8, ¹Adolescent Centre for Rheumatology Research, University College London, London, United Kingdom, ²Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom, ³Centre for Rheumatology Research, University College London, London, United Kingdom, ⁴The Rayne Institute, Arthritis Research UK Centre for Adolescent Rheumatology at University College London, Great Ormond Street Hospital and UCLH, University College London, London, United Kingdom, ⁵Centre for Rheumatology, University College London, London, United Kingdom, ⁶Centre for Rheumatology, Department of Medicine, University College London, London, United Kingdom, ⁷Arthritis Research UK Centre for Adolescent Rheumatology at University College London, Great Ormond Street Hospital and UCLH, University College London, London, United Kingdom, ⁸Centre for Rheumatology Research, University College Hospital London, London, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: autoantibodies, juvenile idiopathic arthritis (JIA), rheumatic disease and rheumatoid arthritis (RA)

Session Information

Date: Monday, November 9, 2015

Title: Pediatric Rheumatology - Clinical and Therapeutic Aspects Posters. Juvenile Arthritis and Miscellaneous Rheumatic Diseases

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Raised levels of Rheumatoid Factor (RhF) and antibodies to citrullinated proteins (ACPA), detected in the clinic using combinations of cyclic citrullinated peptides (CCP), are persistently demonstrated in adult Rheumatoid Arthritis (RA) serology. Multiple isotypes of both autoantibodies can be detected months or years prior to the onset of clinical manifestations. IgG-ACPAs are generally accepted as having greater diagnostic specificity than IgM-RhF, which are present in ~10% of the healthy population. IgG-ACPAs have also been detected in sera of patients with Juvenile Idiopathic Arthritis (JIA); in particular those with IgM-RhF+ve polyarticular JIA (poly-JIA), a subset often considered comparable to adult RA. The prevalence and predictive value of ACPA of IgG, IgM and IgA isotype has been extensively studied in adults with RA, but not, to our knowledge, in a juvenile population. This study profiles a large adolescent JIA cohort using CCP as substrate, with the aim to establish a distinct ACPA phenotype for RhF+ve poly-JIA patients, when compared to other JIA subtypes.

Methods:

Levels of anti-CCP antibodies from a total of 95 patients with poly-JIA (RhF–ve; n=67 and RhF+ve; n=24) were compared with age-matched disease controls (Enthesitis-Related Arthritis (ERA) n=29; Extended-Oligoarthritis (EOA) n= 38) and 31 age-matched healthy controls (HCs). Sera were tested for IgG, IgA and IgM isotypes of anti-CCP, using commercial ELISA plates, coated with second generation citrullinated peptides (CCP2). Cut-offs for positivity were defined by manufacturer’s instructions for IgG-CCP (5U/ml). The median age of the poly-JIA patients was 17.4 yrs (IQ range 15.9 to 19.0), with a median disease duration of 8.6 years. RhF status of the poly-JIA cohort was determined from the clinical records. Statistical analysis determined by Mann-Whitney U test.

Results:

In the poly-JIA cohort 87.5% (21/24) of IgM-RhF +ve patients were IgG-CCP+ve, compared with only 6.0% (4/67) of IgM-RhF-ve patients. Furthermore, when compared to control groups, only 2.6% of EOA patients (1/38) and none of the ERA (0/29) or HCs (0/31) were IgG-CCP positive. When results for IgM-RhF+ve/IgG-CCP+ve (n=21) poly-JIA patients were compared with those of the seronegative poly- JIA cohort (IgM-RhF -ve/IgG-CCP–ve; n=67) levels of IgA-CCP (6.47 (IQ range 4.43-15.74) vs 2.95 (IQ range 2.48-4.37);p<0.0001) and IgM-CCP (69.03 (IQ range 38.03-180.5) vs 40.52 (IQ range 27.0-66.88);p=0.0223) were significantly higher in the seropositive (IgM-RhF+ve/IgG-CCP+ve) group.

Conclusion:

This is the first study to our knowledge that profiles autoantibodies against CCP in a large adolescent JIA patient cohort. Results suggested a significantly higher proportion of poly-JIA patients who are IgM-RhF +ve being IgG-CCP positive when compared to those who were IgM-RhF–ve. Additionally, patients who are IgM-RhF+ve/IgG-CCP+ve had significantly higher levels of both IgA-CCP and IgM-CCP antibodies when compared to patients who were IgM-RhF–ve/IgG-CCP–ve. This data suggests that the serological profile of IgM-RF +ve poly-JIA patients mirrors that described in seropositive adult patients with RA.

Disclosure: H. Peckham, None; L. Bourke, None; A. Radziszewska, None; M. Leandro, None; D. Sen, None; G. Cambridge, None; Y. Ioannou, None.

To cite this abstract in AMA style:

Peckham H, Bourke L, Radziszewska A, Leandro M, Sen D, Cambridge G, Ioannou Y. Anti-Cyclic Citrullinated Peptide Antibody Subclass Phenotypes in Polyarticular Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/anti-cyclic-citrullinated-peptide-antibody-subclass-phenotypes-in-polyarticular-juvenile-idiopathic-arthritis/. Accessed .

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