BACKGROUND: The cellular communication network factor 1 (CCN1) is one of the matricellular proteins of the CCN family involved in chronic inflammatory disorders like rheumatoid arthritis (RA) and involved in human atherosclerotic lesions. This study was aimed to assess the levels of serum CCN1 in patients with rheumatoid arthritis (RA), evaluating its relation to carotid intima-media thickness (CIMT) and predisposition to subclinical carotid atherosclerosis and its impact on activity of RA disease.
MATERIALS AND METHODS: This is a case-control study that included 105 RA patients classified into active and inactive groups according to disease activity score (DAS28) with 50 healthy matched controls. Clinical and laboratory assessments were done including enzyme-linked immunosorbent assay (ELISA) measurement of CCN1 with a bilateral assessment of CIMT using high resolutionultrasonography. Comparison of CCN1 between RA patients and controls, a correlation between CCN1, DAS28, swollen joint count (SJC), tender joint count (TJC), and CIMT were analyzed.
RESULTS: There was significant elevation of CCN1 in RA patients compared to controls (235.62±62.5 vs. 73.11±18.2, respectively). The cut off value of CCN1 was 99.25 pg/ml, with an area under the curve (AUC) =0.995, p<0.001, 98 % sensitivity and 95% specificity. CCN1 was inversely correlated with DAS28 and its components in both active and inactive RA patients (r=- 0.92, r=- 0.94, p<0.001). CCN1 was inversely correlated with SJC (r= -0.64, r= - 0.67, p<0.001), TJC (r=- 0.56, r= - 0.63, p<0.001), and with Larsen xray score (r=- 0.68, r= - 0.78, p<0.001) in both active and inactive RA patients, respectively. The CCN1 levels in active RA patients were significantly lower than that in patients with low disease activity. A significant positive correlation between CCN1 levels and CIMT in RA patient groups (r=0.88, r=0.47, p<0.001, respectively) was found.
CONCLUSION: Serum CCN1 could be a helpful biomarker in the diagnosis of RA, associated with RA remission. Disruption of serum CCN1 is engaged in the pathogenesis of atherosclerosis in RA patients which could be a clue for a future treatment strategy of atherosclerosis in RA by controlling CCN1 disruption. Regular follow-up of RA patients is recommended for early detection of subclinical atherosclerosis. New research ideas for controlling CCN1 disruption as new aspects of atherosclerosis treatment in RA patients are needed.
* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.