4. DISCUSSION
This study first analyzed the association of serum C1q levels with disease activity in a large sample of Chinese TA patients. Our experimental results showed that serum C1q levels were increased in TA patients compared to healthy controls. Notably, TA patients with active disease had higher levels of serum C1q than patients who had inactive disease. Serum C1q levels and traditional inflammatory biomarkers in TA patients correlated positively; therefore, our findings show that serum C1q concentrations is a potential biomarker for evaluating disease activity in TA patients. TA is a systemic autoimmune vasculitis with unknown etiology. Immune mechanisms appear to be involved in TA pathogenesis, as inflammatory cell infiltration along with granulomatous inflammation and excessive proinflammatory cytokine productions are observed in the vascular tissue involved.15 The pathogenesis of systemic vasculitides, including TA, correlates with the presence of inflammatory cells in the arteries and with immune complex (IC) deposition, which cause activation of the complement system, followed by the inflammation and destruction of vascular mural structures.16 Previous studies have found ICs in TA patient sera and on peripheral blood lymphocyte Fc receptors.17 Additionally, a recent paper analyzed the proteomics of circulating ICs in the sera of TA patients and identified three unique antigens.18 Although there are some studies on the relationship between IC and TA, analyses of the association between the complement system and TA have not been reported to date. Moreover, whether activation of the complement system is involved in the pathogenesis of TA remains unclear. C1q, historically viewed as the initiating component of the classical complement pathway, has a diverse range of functions in both innate and acquired immunity. Indeed, C1q plays important roles in the pathogenesis of autoimmune diseases, particularly systemic lupus erythematosus (SLE).19 However, the relationship between C1q and TA remains unresolved. This study is the first to investigate the serum C1q level in Chinese TA patients and its role in the assessment of TA disease activity.
Several studies have suggested the use of serum C1q as an inflammatory marker in multiple diseases. For example, the C1q level in serum is considered an inflammatory marker for disease activity in childhood LN7 and PM/DM.10 Our study found that TA patients with active disease had higher levels of serum C1q than patients who had inactive disease. At the same time, treatment-naïve patients had higher serum C1q levels than those who had always been treated with corticosteroids or at least one immunosuppressant. We found serum C1q levels to correlate significantly with Kerr’s score, ESR and hs-CRP levels in our TA patients. The AUC ofC1qwas lower than that of ESR, but the AUC of C1q was higher than that of hs-CRP. In addition, when the three indicators (C1q, ESR and hs-CRP) were combined, the AUC increased, and a serum cutoff value of 167.15 mg/L C1q maximized the disease activity assessment capacity. The sensitivity of C1q was lower than that of ESR and higher than that of hs-CRP, though the specificity of C1q was lower than that of both ESR and hs-CRP. Additionally, when the three indicators (C1q, ESR and hs-CRP) were combined, the sensitivity increased. Therefore, hs-CRP has the highest specificity, and the sensitivity of combining three indicators (C1q, ESR and hs-CRP) was the highest. Based on the above, we conclude that the concentration of serum C1qisa potential inflammatory marker for TA and that the combination of the above three indicators increases the sensitivity of disease activity assessment.
A limitation of this study is that we did not detect C1q deposited in vascular tissue. As a result, well-designed prospective studies should be performed to clarify the exact clinical molecular mechanisms of C1q in TA patients and the association with TA disease activity.