Hsa_circ_0008301 as a potential biomarker of disease activity for primary Sjogren's syndrome: Increased expression in peripheral blood of patients with primary Sjogren's syndrome.

To explore the expression level, association with disease activity and clinical significance of hsa_circ_0008301 in the peripheral blood of patients with primary Sjögren's syndrome (pSS). We selected 70 pSS patients hospitalized under the Rheumatology service line at the General Hospital of Ningxia Medical University from September 2018 to June 2021 as the disease group, in which general data and clinical indicators were collected. Fifty-three patients with healthy physical examinations for the same period were selected as the healthy control group, and 32 patients with non-pSS rheumatic diseases were selected as the disease control group. We collected peripheral blood samples and used fluorescence quantitative PCR to detect the expression level of hsa_circ_0008301. In addition, we analyzed the association of the expression level of hsa_circ_0008301 with the clinical characteristics and disease activity of pSS patients. A receiver operating characteristic curve was used to evaluate the diagnosis and the disease activity value of hsa_circ_0008301 in patients with pSS. Meanwhile, we analyzed the differential expression of hsa_circ_0008301 in 24 pSS patients selected from the disease group before and after treatment. The relative expression of hsa_circ_0008301 in the peripheral blood of pSS patients was significantly higher than that in the control groups including healthy control group and disease control group. The expression level of hsa_circ_0008301 was high in pSS patients with a course of disease ≥ 10 years, fatigue symptoms, platelets < 100*10^9/L, erythrocyte sedimentation rate ≥ 50 mm/h, immunoglobulin IgG > 16 g/L, complement C3 < 0.9 g/L, ESSDAI score ≥ 5 and positively correlated with the above groups. Furthermore, ROC analysis showed that hsa_circ_0008301 was statistically significant between pSS patients and healthy controls. We selected patients from the disease group before and after treatment and showed that the expression level of hsa_circ_0008301 decreased significantly after treatment, compared with before. The area under the curve (AUC) was 0.825 (95% CI: 0.754 ∼ 0.897; P < 0.0001). The AUC of hsa_circ_0008301 in pSS patients and the disease control group was 0.673 (95% CI: 0.563 ∼ 0.782; P = 0.005), the sensitivity was 40.00%, the specificity was 93.70%, the optimal truncation value was > 0.0420, and the maximum Youden index was 0.337. In addition, ROC analysis revealed that hsa_circ_0008301 was statistically significant between disease-active patients and stable patients. The AUC value was 0.681 (95% CI: 0.553 ∼ 0.809; P = 0.010), the sensitivity was 65.90%, the specificity was 72.40%, the optimal truncation value was > 0.0285, and the maximum Youden index was 0.383. ROC analysis indicated that hsa_circ_0008301 has some value in the diagnosis and disease activity of patients with pSS. Comparison of 24 pSS patients selected from the disease group before and after treatment showed that the expression level of hsa_circ_0008301 decreased significantly after treatment compared with before treatment (Z =  - 4.257, P < 0.0001). ROC analysis indicated that hsa_circ_0008301 has some value in the diagnosis and disease activity of patients with pSS. Hsa_circ_0008301 is expressed in higher levels in the peripheral blood of patients with pSS, which is related to the disease activity. It may be involved in the occurrence and development of pSS and may have a potential biomarker for the disease.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.