Complement activation is a hallmark of systemic lupus erythematosus (SLE) and can
proceed through the classical (CP), lectin (LP), or alternative pathway (AP). When
managing SLE patients, pathway-specific complement activation is rarely monitored
as clinical assays are unavailable. In this study, we aim to differentiate between
CP- or LP-mediated complement activation in SLE patients by quantifying pathway-specific
protein complexes, namely C1s/C1-inhibitor (C1-INH) (CP-specific activation) and MASP-1/C1-INH
(LP-specific activation). Levels for both complexes were assessed in 156 SLE patients
and 50 controls using two newly developed ELISAs. We investigated whether pathway-specific
complement activation was associated with disease activity and lupus nephritis (LN).
Disease activity stratification was performed using SLEDAI scores assessed at inclusion.
C1s/C1-INH concentrations were significantly increased in active SLE patients (SLEDAI
& GE;6) when compared with SLE patients with low disease activity (SLEDAI <6, P <
0.01) and correlated with SLEDAI score (r = .29, P < 0.01). In active LN, MASP-1/C1-INH
plasma concentrations were significantly increased compared with nonactive LN (P =
0.02). No differences in MASP-1/C1-INH plasma concentrations were observed between
active SLE patients and patients with low disease activity (P = 0.11) nor did we observe
a significant correlation with disease activity (r = 0.12, P = 0.15). Our data suggest
that the CP and the LP are activated in SLE. The CP is activated in active SLE disease,
whereas activation of the LP might be more specific to disease manifestations like
LN. Our results warrant further research into specific complement pathway activation
in SLE patients to potentially improve specific-targeted and tailored-treatment approaches.
Complement activation is a hallmark of systemic lupus erythematosus (SLE), but when
managing SLE patients, pathway-specific complement activation is rarely monitored,
as clinical assays are unavailable. In this study, we aim to differentiate between
classical- or lectin pathway-mediated complement activation in 156 SLE patients by
quantifying pathway-specific protein complexes, namely C1s/C1-INH (classical pathway-specific
activation) and MASP-1/C1-INH (lectin pathway-specific activation). Our data suggest
that the classical pathway is activated in active SLE disease, whereas activation
of the lectin pathway might be more specific to disease manifestations like lupus
nephritis.
