Lectin pathway of complement in SLE: MAP-1 as a marker of haematological manifestations and elevated type I interferon activity.

Lindelöf L, Garred P, Hong MG, Wahl Vælum S, Holten Petersen L, Leonard D, Sayadi A, Oke V, Niewold TB, Diaz-Gallo LM, Saevarsdottir S, Gunnarsson I, Svenungsson E, Eriksson O

Lupus Sci Med 13 (1) - [2026-04-09; online 2026-04-09]

SLE is a systemic autoimmune disease in which the complement system plays a key pathogenic role, yet the contribution of the lectin pathway remains unclear. Lectin pathway-dependent complement activation is initiated by pattern-recognition molecules complexed with mannose-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated proteins (MAPs). Here, we combined biochemical and genetic analyses to explore associations between MASP/MAP proteins, SLE manifestations and autoantibody specificities. Serum concentrations of MASP-3, MAP-1 and MASP-2 were measured using ELISA in Swedish patients with SLE (n=522) and population-based matched controls (n=322). Serum type I interferon activity was measured by a cell-based reporter assay. Associations with SLE manifestations and autoantibodies were explored using logistic regression models. Single-nucleotide genetic variants spanning the MASP1 and MASP2 genes were analysed for associations with MASP/MAP levels and SLE manifestations. Patients with MAP-1 serum concentrations in the highest quartile had significantly higher rates of discoid rash (OR 2.8 (95% CI 1.4 to 5.7)), haematological manifestations (OR 2.1 (95% CI 1.1 to 3.7)) and autoantibodies against Sm, RNP, SSA and SSB (ORs 2.4 (95% CI 1.3 to 4.6) to 3.6 (95% CI 1.7 to 7.7)). Patients in the highest quartiles of MAP-1 and MASP-2 had lower rates of anti-β2GP1 and anti-cardiolipin IgG and IgA anti-phospholipid antibodies (ORs 0.29 (95% CI 0.12 to 0.68) to 0.56 (95% CI 0.31 to 1.0)). Serum MAP-1 levels correlated with type I interferon activity (Spearman's rho 0.34, p<0.0001), which mediated the associations of MAP-1 with haematological manifestations and Sm/RNP autoantibodies. Significant protein quantitative trait loci for MAP-1 and MASP-2 were identified; however, these did not show consistent associations with SLE or specific SLE manifestations. These results demonstrate a distinct clinical and serological SLE profile associated with components of the lectin pathway. The lectin pathway-regulatory protein MAP-1 displayed the strongest associations and may serve as a marker of SLE manifestations with a type I interferon signature.

Bioinformatics (NBIS) [Collaborative]

Bioinformatics Support and Infrastructure [Collaborative]

Bioinformatics Support, Infrastructure and Training [Collaborative]

PubMed 41956715

DOI 10.1136/lupus-2025-001890

Crossref 10.1136/lupus-2025-001890

pii: 13/1/e001890