Abstract
Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory
autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and
disability. Although progress has been made in exploring RA nature, still there is a lot to know
about the disease pathogenesis, diagnosis, and treatment.
Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency
musculoskeletal ultrasound used to assess the disease activity and joint damage.
Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA
in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal
ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness {IMT})
were used in assessing the RA disease.
Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1-
8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant
difference. There was a significant positive correlation between anti-carbamylated protein antibodies,
14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by
carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound.
There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein
antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14-3-3η had 51.9% sensitivity and 72.1% specificity.
Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity
in RA diagnosis and had a correlation with the disease activity and joint damage.
Keywords:
Rheumatoid arthritis, anti-carbamylated antibodies, 14-3-3η, musculoskeletal ultrasound, polyarthritis,
diagnosis.
Graphical Abstract
[2]
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016; 388: 2023-38.
[5]
Mäkinen H, Kaarela K, Huhtala H, Hannonen PJ, Korpela M, Sokka T. Do the 2010 ACR/EULAR or ACR 1987 classification criteria predict erosive disease in early arthritis? Ann Rheum Dis 2012; 72-5.
[11]
Willemze A, Toes REM, Huizinga TWJ, Trouw LA. Trouw: new biomarkers in rheumatoid arthritis Netherlands J of Med 2012; 7: 9
[30]
Dawson B, Trapp R. Basic and Clinical Biostatistics 4th Edition, New York, United States Mcgraw-Hill Medical Publishing Inc 2004; 23(61): 245.
[35]
Maksymowych WP, Marotta A. 14-3-3η: a novel mediator upregulated by TNFα, reflects clinical response to anti-TNFα therapy. Arthritis Rheum 2011; (63): (Suppl. 10): S162-3.
[36]
Othman MA, Wan WS, Ghazal M. Hamid WZWA, Won KK, Yahya NK. Anti-carbamylated protein antibodies in rheumatoid arthritis patients and their association with rheumatoid factor. Saudi Med J 2017; 38-9.
[39]
Kucuksahin BO, Yeşil TH, Akan S, Erten S. Sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis 2018; 77-2.
[41]
Novikov A, Aleksandrova E, Cherkasova M, et al. diagnostic value of 14-3-3 (eta) in rheumatoid arthritis. Annals of The Rheum Dis 2017; 76:(Suppl 2).
[43]
Dasgupta B, Cherkas Y, Lamberth S, et al. Serum 14-3-3 ETA is an RA specific mechanistic marker. J Rheumatol 2014; 41(11): 2104.
[44]
Serum level of 14-3-3η (eta) protein as a diagnostic marker for rheumatoid arthritis and potential correlation with disease activity. MOJ Orthop Rheumatol 2018; 7-4.
[45]
Zickuhr L, Pourpaki M, Brooks MM, Joseph A. 14-3-3η: Useful for more than the diagnosis of rheumatoid arthritis? Arthritis Rheumatol 2017; 69: (suppl 10)
[46]
Schaardenburg DV, Turk S, Bores M, Walter M. 14-3-3η is an independent predictor of radiographic changes in early RA and higher titers inform a higher likelihood of joint damage progression. Ann Rheum Dis 2014; 73(Suppl. 2): 266.
[48]
Berglin E, Hallmans G. Serum 14-3-3η predicts the risk of RA development and its higher titers are associated with higher risk. Ann Rheum Dis 2014; 73.
[49]
Chao R, Das M, Purat N, et al. 14–3–3eta positivity is associated with higher rheumatoid arthritis disease activity measured by multi-biomarker disease activity assay. Ann Rheum Dis 2018; 77: 1326-7.
[54]
Yee A, Webb T, Seaman A, et al. Anti-CarP antibodies as promising marker to measure joint damage and disease activity in patients with rheumatoid arthritis. Immunol Res 2015; 61: 24-30.
[55]
Jagpal A, Navarro-Millan I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment, and treatment Jagpal and Navarro-Millán BMC Rheumatol 2018; 2(10)