Background/Purpose:  Chikungunya fever virus (CHIK) is emerging in the western hemisphere as a mosquito-borne, acute onset arthritis. The majority of cases progress to persistent moderate to severe polyarthritis that clinically resembles rheumatoid arthritis (RA).¹ As the majority of CHIK arthritis patients reportedly lack rheumatoid factor (RF) and cyclic citrullinated peptide antibody (CCP), differential diagnosis includes seronegative RA.²  Extracellular 14-3-3η, a chaperonin, is a novel biomarker for joint damage in rheumatoid arthritis (RA) and erosive psoriatic arthritis, with serum elevation occurring in early RA. We previously demonstrated that 21% of patients with early “seronegative” RA and 67% of patients with established “seronegative” RA are 14-3-3η-positive.³In order to determine the utility of RF, CCP, and 14-3-3η in the differential diagnosis of CHIK arthritis versus RA, we tested CHIK infected patient serum for 14-3-3η.

Methods:  Serum samples were submitted for CHIK IgM and IgG serology. De-identified remnant samples positive for CHIK IgM were tested for 14-3-3η by a proprietary laboratory-developed sandwich ELISA. Rheumatoid factor (RF) isotypes and cyclic citrullinated peptide antibody (CCP) were determined by ELISA.

Results:  Of 234 CHIK IgM-positive sera, 223 were also CHIK IgG-positive (95.3%, CI 91.7% to 97.6%). RF IgM was positive in 51 of the CHIK IgM-positive patients (21.8%, CI 16.7% to 27.6%), RF IgG in 7 (3.0%, CI 1.2% to 6.1%), and RF IgA in 10 (4.3%, CI 2.1% to 7.7%). CCP was positive in only 4 patients (1.7%, CI 0.5% to 4.3%). Two isotypes of RF were present in 7 patients, only one of which was CCP-positive. All 3 RF isotypes were present in 1 patient, but the patient was CCP-negative. At least one isotype of RF was positive in 59 patients (25.2%, CI 19.8% to 31.3%). 14-3-3η was positive in 25 patients (10.7%, CI 7.0% to 15.4%). Of those 25, RF was positive in only 6 (24.0%, CI 9.4% to 45.1%) and CCP was positive in only 2 (8.0%, CI 1.0% to 26.0%).

Conclusion:  Nearly all patients were positive for CHIK IgG at the time of diagnosis based on a positive CHIK IgM. At least one RF isotype was present in 25.2% of patients. CCP was uncommon. 14-3-3η was present in only 10.7% in contrast to a 64% positivity rate in early RA patients.⁴  Therefore, RF may not be helpful in differentiating early RA from CHIK arthritis. However, CCP and 14-3-3η occur less frequently in CHIK arthritis and when present may aid in the differential diagnosis of RA from CHIK arthritis.

References: 1. Arroyo-Avila, Vilá. P R Health Sci J. 34:71-77, 2015; 2. Miner et al. Arth Rheum 67:1214-20, 2015; 3. Naides, Marotta. J Rheum, in press; 4.. Maksymowych, et al. J Rheum. 41:2104-13, 2014.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/chaperonin-protein-14-3-3eta-cyclic-citrullinated-peptide-antibody-and-rheumatoid-factor-in-the-differential-diagnosis-of-chikungunya-arthritis-versus-rheumatoid-arthritis/