Lectin pathway components and autoantibodies as novel immunological biomarkers in systemic lupus erythematosus (SLE) patients from Western India

TL;DR

This study identifies lectin pathway components and autoantibodies as potential biomarkers for systemic lupus erythematosus in patients from Western India.

Contribution

The study introduces lectin pathway molecules and their autoantibodies as novel immunological biomarkers for SLE.

Findings

Serum levels of ficolin-2, MASP-3, and MAp44 are elevated in SLE patients.

Autoantibodies against ficolin-1, ficolin-2, and ficolin-3 are significantly elevated in SLE patients.

Anti-MBL antibodies correlate with SLE disease activity and anti-dsDNA antibodies.

Abstract

The lectin pathway of complement aids in removing apoptotic cells and maintenance of tissue homeostasis. However, its role in SLE pathogenesis remains unknown. This study aimed to assess the association of ficolins, mannose-binding lectin (MBL), and other pathogen recognition molecules (PRMs) of the lectin pathway and their corresponding autoantibodies with various clinical manifestations and disease activity in SLE patients from Western India. In this cross-sectional study, 282 clinically diagnosed SLE patients were included. Serum levels of ficolins, antigenic MBL, MBL-associated serine proteases (MASPs), MBL-associated protein 44 (MAp44), Collectin liver-1 (CL-L1), and their corresponding autoantibodies were quantified using ELISA. Group differences were analyzed using Mann-Whitney U tests, while associations/relationships were evaluated using chi-square tests and Spearman’s correlations. Serum levels of ficolin-2 (p < 0.001), MASP-3 (p = 0.030), and MAp44 (p < 0.001) were significantly elevated, while antigenic MBL (p < 0.001) and MASP-1 (p < 0.001) were significantly reduced in SLE patients compared to healthy controls (HCs). Renal involvement was associated with elevated ficolin-1 (p = 0.009), while hematological manifestations were linked to reduced MASP-1 (p = 0.018), MASP-3 (p = 0.002), and MAp44 (p = 0.002) levels. Mucocutaneous manifestations were associated with elevated MAp44 (p < 0.001) and anti-ficolin-1 (p = 0.038) autoantibodies. Anti-ficolin-1 (p = 0.001), anti-ficolin-2 (p = 0.001), and anti-ficolin-3 (p < 0.001) autoantibodies were significantly elevated in SLE patients compared to HCs. Anti-ficolin-2 autoantibodies were negatively correlated with ficolin-2 (r=-0.153, p = 0.015). Anti-MBL antibodies were correlated with SLEDAI (r = 0.169, p = 0.007) and anti-dsDNA antibodies (r = 0.178, p = 0.005). These findings indicate altered levels of lectin pathway-associated PRMs and their corresponding autoantibodies in SLE. Their association with clinical manifestations, disease activity, and complement-related parameters, suggest their potential as novel biomarkers in SLE.

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