Serum Amyloid A Is a Biomarker of Disease Activity and Health-Related Quality-of-Life in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Abstract

Serum amyloid A (SAA) is one of the acute phase proteins synthesized in hepatocytes and secreted by various inflammation or infectious stimuli. We investigated the clinical implication of measuring SAA in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Seventy-five patients who had been classified as AAV and enrolled in our prospective observational cohort for AAV patients were included. Clinical and laboratory data were obtained on the day of blood sampling, and SAA was measured by ELISA kits. Birmingham Vasculitis Activity Score (BVAS) and Short-Form 36-Item Health Survey (SF-36) were assessed for disease activity and health-related quality-of-life (HRQoL) measures. We stratified patients into having high BVAS when the BVAS was over the median values, and those with either low SF-36 PCS or low SF-36 MCS were defined as having poor HRQoL. Multivariate logistic regression analysis was conducted to estimate independent predictors of high BVAS. The relative risk (RR) was analyzed using the contingency tables and the chi-squared test. SAA was positively correlated with BVAS ( r = 0.642 ) and FFS ( r = 0.367 ) and was inversely correlated with both the SF-36 physical component summary ( r = − 0.456 ) and mental component summary scores ( r = − 0.394 ). Furthermore, SAA was significantly correlated with acute phase reactants ESR ( r = 0.611 ) and CRP ( r = 0.629 ). Patients with high BVAS exhibited significantly higher SAA than those with low BVAS (1317.1 ng/mL vs. 423.1 ng/mL). In multivariable logistic regression analysis, serum albumin (odds ratio (OR) 0.132) and SAA > 1173.6 ng / mL (OR 15.132) were independently associated with high BVAS. The risk of having high BVAS and poor HRQoL in patients with SAA > 1173.6 ng / mL was higher than in those with SAA ≤ 1173.6 ng / mL (RR 3.419 and 1.493). Our results suggest that SAA might be a useful biomarker in assessing disease activity and HRQoL in AAV.

Clinical features and markers to identify pulmonary lesions caused by infection or vasculitis in AAV patients

“…Some biomarkers such as PCT, CRP, SAA, and ESR are helpful in the identification of infection [ 8 , 9 , 23 – 27 ], yet remain unclear for AAV patients. According to previous studies, it seems that higher CRP is more likely to indicate lung infection [ 24 ], while ESR is more likely to indicate AAV activity [ 28 ].…”

“…To avoid the improper treatment of pulmonary complications in AAV patients, it is urgent to identify reliable markers to distinguish the pulmonary lesions of infection and vasculitis. Recently, a panel of biomarkers, including neutrophil-to-lymphocyte ratio (NLCR), serum amyloid A (SAA), as well as pro-calcitonin (PCT) have been used to identify and assess the infectious status in clinics [ 8 , 9 ]. However, to our knowledge, similar markers for assessing the infection of AAV patients have not yet been fully explored.…”

Clinical features and markers to identify pulmonary lesions caused by infection or vasculitis in AAV patients

“…However, PR3 and MPO titers were not signi cantly different between the LI and NI groups, suggesting that patients with high PR3 and MPO may be more likely to have pulmonary lesions, but these two indexes cannot predict whether they were complicated by a lung infection. Some biomarkers such as PCT, CRP, SAA, and ESR are helpful in the identi cation of infection [8,9,[20][21][22][23] , yet remain unclear for AAV patients. According to previous studies, it seems that higher CRP is more likely to indicate lung infection [24] , while ESR is more likely to indicate AAV activity [25] .…”

“…To avoid the improper treatment of pulmonary complications in AAV patients, it is urgent to identify reliable markers to distinguish the pulmonary lesions of infection and vasculitis. Recently, a panel of biomarkers, including neutrophil-to-lymphocyte ratio (NLCR), serum amyloid A (SAA), as well as pro-calcitonin (PCT) have been used to identify and assess the infectious status in clinics [8,9] . However, to our knowledge, similar markers for assessing the infection of AAV patients have not yet been fully explored.…”

Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients

“…The role of SAA in autoimmunity is underscored by data showing that SAA are associated with clinical severity and disease susceptibility. Several authors, comparing serum SAA levels between healthy and diseased individuals, showed an increase in SAA concentration during autoimmune diseases (Ahmed et al., 2022; Shen et al., 2015; Wang et al., 2020; Yoon et al., 2020). Notably, SAA can act directly on T cells and promote Th17 cell programming and response amplification, which revealed in inflammatory bowel disease (IBD) and experimental autoimmune encephalomyelitis (EAE) models (Lee et al., 2020).…”