14-3-3η Protein in Rheumatoid Arthritis: Promising Diagnostic Marker and Independent Risk Factor for Osteoporosis

Tingting Zeng, MD; Liming Tan, MD; Yang Wu, MD; Jianlin Yu, MD

Disclosures

Lab Med. 2020;51(5):529-539. 

In This Article

Abstract and Introduction

Abstract

Background: Early identification and disease monitoring are challenges facing rheumatologists in the management of rheumatoid arthritis (RA).

Methods: We utilized enzyme-linked immunosorbent assay (ELISA) to determine 14-3-3η and anticyclic citrullinated peptide antibody (anti-CCP) levels, with rheumatoid factor (RF) level detected by rate nephelometry. The diagnostic value of each index was determined via receiver operating characteristic (ROC) curve, and the association between 14-3-3η and osteoporosis was assessed using multiple logistic regression analysis.

Results: Serum levels of 14-3-3η were 3.26 ng per mL in patients with RA. These levels were helpful in identifying patients with the disease, with the area under the curve (AUC) being 0.879 and 0.853, respectively, from all healthy control individuals and patients with RA. Combining 14-3-3η with RF or anti-CCP increased the diagnostic rate. Logistic regression analysis identified 14-3-3η as an independent risk factor for RA-related osteoporosis (odds ratio [OR], 1.503; 95% confidence interval [CI], 1.116–2.025; P <.01).

Conclusions: Serum 14-3-3η detection by itself or combined with other serum indices was helpful in differentiating patients with RA. Also, it was a promising biomarker for disease monitoring in RA.

Introduction

Rheumatoid arthritis (RA) is a clinically common autoimmune disease, characterized by chronic arthritis of bilateral small joints, which causes bone and joint erosion and terminal functional deficiency.[1] As a major contributor to bone-mass reduction and osteoporosis, owing to long-term systemic inflammation and use of corticosteroids, RA seriously impaired patient quality of life.[2,3] Rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) are traditional serum biomarkers for RA diagnosis and classification.[4,5] Combined with articular symptoms and radiographic evidence, these biomarkers assist rheumatologists in confirming which patients have typically symptomatic RA. However, the manifestations of RA are too diversified for physicians to distinguish the not-well-differentiated symptoms in patients harboring other diseases that share common clinical features with RA.[1] As a result, many patients, particularly those with earlier-stage and/or serum-negative results, experience misdiagnosis or missed diagnosis. Therefore, it is highly urgent to discover useful biomarkers, to improve current diagnostic and disease-monitoring levels. Accumulating evidence[6,7] has indicated that 14-3-3η protein is elevated in patients with RA and has contributed to the upregulation of RA-related proinflammation mediator expression and joint damage.

In the present study, we used enzyme linked immunosorbent assay (ELISA) in our testing. Our goals were to evaluate the diagnostic value of serum 14-3-3η levels and to explore the association of this biomarker with osteoporosis in patients with RA.

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