Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Spondyloarthritis (SpA) represents a group of immune-mediated inflammatory diseases that exhibit overlapping clinical features, genetic predisposition and a not fully understood pathogenesis. Inflammation and structural damage of target tissue are clinical characteristics. Growing evidence indicates that parts of the pro-inflammatory profile in SpA is caused by abnormal innate immune responses. In SpA it is believed that immune system failures result in insufficient removal of dead cells from the body, leading to an increased or abnormal pressure on the immune system. This may lead to activation of the Lectin Pathway (LP) of the complement system. The LP of the complement system plays a role in the clearance of apoptotic and necrotic cells. We hypothesize that a characterization of the lectin pathway proteins in SpA patients compared to controls may provide new insight into the pathogenesis of SpA.
Methods: Prospectively, blood samples (EDTA plasma) and disease activity scores (ASDAS, BASDAI and BASMI) were collected in a well-defined cross sectional SpA cohort of 120 patients (median age 36.5 years, range 18-72; 85% HLA-B27 positive, 61% male; 45% bDMARD treated) fulfilling the ASA 2009 criteria and of 120 controls. Ten proteins of the LP were measured in plasma using in-house developed assays. As indicators of complement consumption and activation the complement proteins C3 and C3dg were assessed.
Concentrations of the LP proteins were altered in a specific pattern in this cross-sectional SpA cohort compared with healthy controls. High concentrations in plasma of H-ficolin, MAp44 and M-ficolin and low concentrations of CL-L1 were observed for patients with SpA compared to healthy individuals (p-values all <0.001). The differences in LP proteins observed between patients and controls were not significantly associated with complement activation or disease activity (ASDAS, BASDAI). Using the 75-percentile in healthy controls as cut-off for an elevated concentration of H-ficolin, MAp44, and M-ficolin and the 25-percentile as cut-off for a reduced concentration in CL-L1, we then used resulting elevated or reduced values as disease biomarkers. Using the cumulative presence of the four altered LP concentrations in patients and controls, we could to a high degree separate SpA patients from healthy controls. Among controls with LP concentrations within the normal range a negative predictive value of 0.90 was found and among SpA patients with three altered LP concentrations a positive predictive value of 0.87 was found.
In this cross-sectional SpA cohort we observed specific changes in 4 of 10 LP proteins. The specific pattern (high H-ficolin, L-ficolin, MAp44 and low CL-L1) clearly differentiated to a high degree SpA patients from healthy individuals. Potentially, this could improve the diagnosis of SpA. These novel findings may substantiate the involvement of LP proteins in the pathogenesis of SpA.
To cite this abstract in AMA style:Troldborg A, Thiel S, Mistegaard Joergensen C, Stengaard-Pedersen K, Loft AG. Unique Pattern of Lectin Pathway Complement Protein Levels in Axial Spondyloarthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/unique-pattern-of-lectin-pathway-complement-protein-levels-in-axial-spondyloarthritis/. Accessed March 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/unique-pattern-of-lectin-pathway-complement-protein-levels-in-axial-spondyloarthritis/