Importance of 14-3-3eta, anti-CarP, and anti-Sa in the diagnosis of seronegative rheumatoid arthritis

Abstract

Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation. The study aimed to assess serum 14-3-3eta, anti-CarP, and anti-Sa in seronegative RA (SNRA) patients who were treatment-naïve as well as in healthy subjects. This is the first study in the literature to examine these autoantibodies together in SNRA patients. Materials and methods: Forty-five treatment-naïve SNRA patients and 45 healthy subjects were recruited. Drugs change the levels of autoantibodies; therefore, patients who took any medication had been excluded from our study. Anti-carbamylated protein, anti-Sa, and 14-3-3eta were measured by using three different ELISA kits. Results: Median serum concentration of healthy controls in 14-3-3eta was 0.02 (0.02-0.27) ng/mL. Median serum concentration of SNRA patients in 14-3-3eta was 1.00 (0.48-1.28) ng/mL. Data were analyzed with Mann-Whitney U tests; the P-value was <0.001 in 14-3-3eta. Receiver operating characteristic (ROC) curve analysis showed that 14-3-3eta in SNR compared to healthy controls had a significant (P < 0.001) area under the curve (AUC) of 0.90 (95% confidence interval, 0.83-0.96). At a cutoff of ≥0.33 ng/mL, the ROC curve yielded a sensitivity of 88.9%, a specificity of 82.2%, a positive predictive value of 83.3%, and a negative predictive value of 88.1%. Conclusion: We found that 14-3-3eta can be used as a diagnostic marker in SNRA.

Diagnostic accuracy of 14‐3‐3 η protein in rheumatoid arthritis: A meta‐analysis

“…Next, we carried out the subgroup analysis by Meta‐Disc 1.4 based on gender ratio, mean age, ethnicity, case number of RA patients, control groups, and study design. As shown in Table , after grouping, both the inconsistency (1‐square) of pooled sensitivity and specificity decreased in African and European groups, in Asian populations, 15,17,24‐26,28,29 the pooled sensitivity had no apparent change (0.73 [0.71‐0.75]) and the pooled specificity increased (0.91 [0.89‐0.93]); in African populations, 18,27,30 both the pooled sensitivity (0.88 [0.82‐0.93]) and specificity (0.91 [0.85‐0.95]) augmented; however, in European groups, 16,31,32 the pooled sensitivity (0.67 [0.63‐0.71]) and specificity (0.83 [0.80‐0.86]) declined. As shown in Table , in healthy and disease control, 16‐18,25,26,28‐32 the diagnostic value of pooled sensitivity decreased to 0.67 (0.65‐0.70) and pooled specificity had no apparent change (0.88 [0.86‐0.90]); however, in healthy controls, 15,24,27 both the pooled sensitivity (0.96 [0.93‐0.98]) and specificity (0.90 [0.84‐0.95]) increased, and both the inconsistency (1‐square) of pooled sensitivity and specificity decreased.…”

“…Salman et al found that 40 (88%) of their 45 patients who were seronegative for RF and ACPA were 14-3-3η-positive and suggested that 14-3-3η protein is a valuable and promising marker in patients with SNRA. 24 Another of the advantages of 14-3-3 η protein as an RA marker is that adding 14-3-3 η to RF or ACPA or the combination of all 3 markers would increase the diagnostic rate. Guan et al found that adding 14-3-3 η to RF and ACPA testing increased diagnostic sensitivity for early RA patients.…”

“…One of the advantages of 14‐3‐3η protein as an RA marker is that it can improve identification rates of seronegative RA (SNRA). Salman et al found that 40 (88%) of their 45 patients who were seronegative for RF and ACPA were 14‐3‐3η‐positive and suggested that 14‐3‐3η protein is a valuable and promising marker in patients with SNRA 24 . Another of the advantages of 14‐3‐3 η protein as an RA marker is that adding 14‐3‐3 η to RF or ACPA or the combination of all 3 markers would increase the diagnostic rate.…”

“…Next, we carried out the subgroup analysis by Meta-Disc 1.4 based on gender ratio, mean age, ethnicity, case number of RA patients, control groups, and study design. As shown in Table S1, after grouping, both the inconsistency (1-square) of pooled sensitivity and specificity decreased in African and European groups, in Asian populations, 15,17,[24][25][26]28,29 the pooled sensitivity had no apparent change Table S1, in healthy and disease control, [16][17][18]25,26,[28][29][30][31][32] the diagnostic value of pooled sensitivity decreased to 0.67 (0.65-0.70) and pooled specificity had no apparent change (0.88 [0.86-0.90]); however, in healthy controls, 15,24,27 both the pooled sensitivity (0.96 [0.93-0.98]) and specificity (0.90 [0.84-0.95]) increased, and both the inconsistency (1-square) of pooled sensitivity and specificity decreased. Overall, these results suggested that ethnicity and control groups may be a major source of heterogeneity.…”

“…A total of 381 records were identified through databases (PubMed, EMBASE, and Web of Science) and by scrutinizing the reference lists F I G U R E 1 Flow diagram of screening studies of the included studies, [15][16][17][18][24][25][26][27][28][29][30][31][32] of which 164 were excluded on account of duplicate records. Following thorough screening of the titles and abstracts, we excluded 136 of the remaining 217 studies due to no relevance to the topic or they were animal experiments.…”