Autoantibodies against pentraxin-3 in systemic lupus erythematosus: mapping of reactivity to linear epitopes and associations with disease variables

The pentraxin-3 (PTX3) protein can activate and modulate complement and immune cells. IgG anti-PTX3 antibodies are suggested to protect against lupus nephritis (LN). This study aimed to evaluate anti-PTX3 IgG antibody levels across three rheumatic diseases, investigate the linear epitopes of PTX3, and identify potential clinical associations in systemic lupus erythematosus (SLE). A subsequent aim was to examine neutrophil immunoregulatory effects of selected epitopes as synthesized peptides. Microarray-based linear epitope mapping of PTX3 was performed, and neutrophils isolated from blood of healthy blood donors (HBD) to assess potential peptide-mediated effects. Anti-PTX3 levels did not differ between patients with SLE and those with other rheumatic diseases or HBD but were significantly lower in active SLE than in clinically quiescent SLE. In SLE, 17 unique PTX3 antibody epitopes were identified, and epitope-specific antibodies were associated with complement consumption, active SLE, and LN. Epitope-based synthetic peptides can inhibit the neutrophil oxidative burst. In conclusion, anti-PTX3 antibodies in SLE show substantial epitope spreading compared to healthy individuals, while their levels are significantly lower in patients with active SLE. Some of these epitopes are associated with the clinical features of SLE. As peptides, selected PTX3 epitopes might exert immunomodulatory functions on neutrophils.