C1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule That Recruits Collectin-11 from the Complement System to Ligands.

C1q/TNF-related protein (CTRP) 6 is a member of the CTRP protein family associated with the regulation of cellular and endocrine processes. CTRP6 contains collagen and globular structures, resembling the pattern recognition molecules (PRMs) of the classical and lectin complement pathways. We expressed human CTRP6 in Chinese hamster ovary cells and investigated the binding to different putative ligands (acetylated BSA [AcBSA], zymosan, mannan, and LPS from Escherichia coli and Salmonella as well as to the monosaccharides l-fucose, d-mannose, N-acetylglucosamine, N-acetylgalactosamine, and galactose). Furthermore, we investigated the binding of CTRP6 to various Gram-negative bacteria as well as PRMs and enzymes of the lectin complement pathway. We found that CTRP6 bound to AcBSA and to a lesser extent to zymosan. Using EDTA as chelating agent, we observed an increased binding to AcBSA, zymosan and the two strains of LPS. We detected no binding to mannan and BSA. We identified l-fucose as a ligand for CTRP6 and that it bound to certain enteroaggregative Escherichia coli and Pseudomonas aeruginosa isolates, whereas to other bacterial isolates, no binding was observed. CTRP6 did not appear to interact directly with the activating enzymes of the lectin pathway; however, we could show the specific recruitment of collectin-11 and subsequent initiation of the complement cascade through deposition of C4. In conclusion, our results demonstrate the binding of CTRP6 to a variety of microbial and endogenous ligands identifying CTRP6 as a novel human lectin and PRM of importance for complement recognition and innate immunity.

Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway.

The complement system, a part of the innate immune system, can be activated via three different pathways. In the alternative pathway, a factor D (FD) plays essential roles in both the initiation and the amplification loop and circulates as an active form. Mannose-binding lectin-associated serine proteases (MASPs) are key enzymes of the lectin pathway, and MASP-1 and/or MASP-3 are reported to be involved in the activation of FD. In the current study, we generated mice monospecifically deficient for MASP-1 or MASP-3 and found that the sera of the MASP-1-deficient mice lacked lectin pathway activity, but those of the MASP-3-deficient mice lacked alternative pathway activity with a zymogen FD. Furthermore, the results indicate that MASP-3 but not MASP-1 activates the zymogen FD under physiological conditions and MASP-3 circulates predominantly as an active form. Therefore, our study illustrates that, in mice, MASP-3 orchestrates the overall complement reaction through the activation of FD.

Plasma levels of H- and L-ficolin are increased in axial spondyloarthritis: improvement of disease identification.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton. A predominance of innate versus adaptive immune responses have been reported in axSpA, indicating a prominent autoinflammatory component of the disease. Little is known about the lectin pathway proteins (LPPs) of the complement system in relation to axSpA. We have investigated LPPs in patients with axSpA and control individuals. Plasma samples were obtained from a cross-sectional cohort of 120 patients with a clinical diagnosis of axSpA and from 144 age- and gender-matched controls. The plasma concentrations of 11 LPPs were measured, using sandwich-type time-resolved immunofluorometric assays in patients and controls, and related to clinical diagnosis and disease activity. Three LPPs [H-ficolin (ficolin-3), L-ficolin (ficolin-2) and collectin liver 1 (CL-L1)] were significantly higher in axSpA patients than in controls (P < 0·0001) and one LPP, collectin kidney 1 (CL-K1), was significantly lower (P < 0·0001). Further, combining H- or L-ficolin concentrations above the 75th percentile of the respective H- or L-ficolin concentration measured in controls with human leucocyte antigen (HLA)-B27 positivity yielded axSpA diagnostic specificities of 99/99% and positive likelihood ratios of 68/62, respectively. H-ficolin and L-ficolin plasma concentrations were found to be elevated in axSpA patients regardless of time since diagnosis. H-ficolin and L-ficolin may represent diagnostic biomarkers for patients with axSpA and should be further evaluated. Our results showed no association between disease activity and the measured LPP concentrations. This result might be due to the cross-sectional design, and should be further investigated.

Serum mannose-binding lectin (MBL) concentrations are reduced in non-pregnant women with previous adverse pregnancy outcomes.

Mannose-binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro-organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non-pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%-100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%-97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%-83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%-83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

Cutting Edge: A New Player in the Alternative Complement Pathway, MASP-1 Is Essential for LPS-Induced, but Not for Zymosan-Induced, Alternative Pathway Activation.

The complement system is a sophisticated network of proteases. In this article, we describe an unexpected link between two linear activation routes of the complement system: the lectin pathway (LP) and the alternative pathway (AP). Mannose-lectin binding-associated serine protease (MASP)-1 is known to be the initiator protease of the LP. Using a specific and potent inhibitor of MASP-1, SGMI-1, as well as other MASP-1 inhibitors with different mechanisms of action, we demonstrated that, in addition to its functions in the LP, MASP-1 is essential for bacterial LPS-induced AP activation, whereas it has little effect on zymosan-induced AP activation. We have shown that MASP-1 inhibition prevents AP activation, as well as attenuates the already initiated AP activity on the LPS surface. This newly recognized function of MASP-1 can be important for the defense against certain bacterial infections. Our results also emphasize that the mechanism of AP activation depends on the activator surface.

Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury. METHODS: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up. RESULTS: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed. CONCLUSIONS: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

Enterococcus faecalis Escapes Complement-Mediated Killing via Recruitment of Complement Factor H.

BACKGROUND: Enterococcus faecalis is considered to be the most important species of enterococci responsible for blood stream infections in critically ill patients. In blood, the complement system is activated via the classical pathway (CP), the lectin pathway (LP), or the alternative pathway (AP), and it plays a critical role in opsonophagocytosis of bacteria including E faecalis. METHODS: In a mouse model of enterococcus peritonitis, BALB-C mice were challenged with a high dose of E faecalis 12 hours after intraperitoneal administration of anti-Factor H (FH) antibodies or isotype control. Four hours later, control mice developed higher bacterial burden in blood and organs compared with mice treated with anti-FH antibodies. RESULTS: We demonstrate that complement recognition molecules C1q, CL-11, and murine ficolin-A bind the enterococcus and drive the CP and the LP in human and mouse. We further describe that E faecalis evades the AP by recruitment of FH on its surface. Our results show a strong C3b deposition on E faecalis via both the CP and the LP but not through the AP. CONCLUSIONS: These findings indicate that E faecalis avoids the complement phagocytosis by the AP via sequestering complement FH from the host blood.

C4d in Native Glomerular Diseases.

Complement activation occurs in many glomerular diseases, the exact pathway(s) of activation has been studied in detail in some diseases but not in all. C4d is generated by the activation of classical and lectin pathways, and its presence can point to the activation of either of these pathways. This review aims to summarize the available data with regard to the deposition of glomerular C4d in native kidney biopsies in different glomerular pathologies that may be useful for future research into the role of complement activation in glomerular diseases. While there is more information on C4d in certain diseases (e.g., Immunoglobulin A (IgA) nephropathy), there is scant data in other diseases (such as focal segmental glomerulosclerosis).

The Group B Streptococcus-Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways.

The group B Streptococcus (GBS) is a leading cause of neonatal invasive disease. GBS bacteria are surrounded by a thick capsular polysaccharide that is a potent inhibitor of complement deposition via the alternative pathway. Several of its surface molecules can however activate the classical and lectin complement pathways, rendering this species still vulnerable to phagocytic killing. In this study we have identified a novel secreted protein named complement interfering protein (CIP) that downregulates complement activation via the classical and lectin pathways, but not the alternative pathway. The CIP protein showed high affinity toward C4b and inhibited its interaction with C2, presumably preventing the formation of the C4bC2a convertase. Addition of recombinant CIP to GBS cip-negative bacteria resulted in decreased deposition of C3b on their surface and in diminished phagocytic killing in a whole-blood assay. Our data reveal a novel strategy exploited by GBS to counteract innate immunity and could be valuable for the development of anti-infective agents against this important pathogen.

Lectin complement pathway proteins in healthy individuals.

Since the discovery of the lectin pathway of complement activation, numerous clinical cohorts have been examined for one or more proteins, with the intention of uncovering the functions of the proteins or with the aim of discovering new biomarkers or diagnostic tools. To unveil the abnormal, it is pivotal to know the normal. Our aim was to describe the concentrations of the 11 known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigation in different cohorts. We examined the concentrations of all lectin pathway proteins mannan-binding lectin (MBL), H-ficolin, L-ficolin, M-ficolin, collectin-K1, collectin-L1, MBL-associated serine protease 2 (MASP-2), MASP-3, MBL-associated protein of 44 kDa (MAp44) and MAp19 in 300 Danish blood donors in serum and ethylenediamine tetraacetic acid (EDTA) plasma in established assays, and we further developed a new assay to measure MASP-1 in the same samples. We found significant differences in concentrations between serum and plasma for all proteins except for MBL and MASP-3. H-ficolin, M-ficolin and MAp19 displayed convincing diurnal variation. H-ficolin, in particular, halved from morning to the middle of the night. There were gender differences for most proteins, whereas age did not seem to influence concentration. The present study underlines the necessity of considering which material to use, correct matching and a trial design that takes the nature of the protein into account in order for the outcome of cohort studies to have significant relevance.

Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.

Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators.

A Metalloproteinase Mirolysin of Tannerella forsythia Inhibits All Pathways of the Complement System.

Recent reports focusing on virulence factors of periodontal pathogens implicated proteinases as major determinants of remarkable pathogenicity of these species, with special emphasis on their capacity to modulate complement activity. In particular, bacteria-mediated cleavage of C5 and subsequent release of C5a seems to be an important phenomenon in the manipulation of the local inflammatory response in periodontitis. In this study, we present mirolysin, a novel metalloproteinase secreted by Tannerella forsythia, a well-recognized pathogen strongly associated with periodontitis. Mirolysin exhibited a strong effect on all complement pathways. It inhibited the classical and lectin complement pathways due to efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4, whereas inhibition of the alternative pathway was caused by degradation of C5. This specificity toward complement largely resembled the activity of a previously characterized metalloproteinase of T. forsythia, karilysin. Interestingly, mirolysin released the biologically active C5a peptide in human plasma and induced migration of neutrophils. Importantly, we demonstrated that combination of mirolysin with karilysin, as well as a cysteine proteinase of another periodontal pathogen, Prevotella intermedia, resulted in a strong synergistic effect on complement. Furthermore, mutant strains of T. forsythia, devoid of either mirolysin or karilysin, showed diminished survival in human serum, providing further evidence for the synergistic inactivation of complement by these metalloproteinases. Taken together, our findings on interactions of mirolysin with complement significantly add to the understanding of immune evasion strategies of T. forsythia and expand the knowledge on molecular mechanisms driving pathogenic events in the infected periodontium.

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery.

The systemic inflammatory response is a challenge in the management of paediatric patients undergoing cardiac surgery. Although multi-factorial, a contribution by the lectin pathway of complement activation has been postulated. We therefore investigated the changes in serum levels of mannose binding lectin (MBL) and activities of MBL-MBL-associated serine protease (MASP)-1 and MBL-MASP-2 complexes immediately before and during surgery, throughout the first postoperative day and at discharge from the hospital. These changes were analysed in relation to postoperative complications. Blood samples were obtained from 185 children with congenital heart disease undergoing surgical correction with the use of cardiopulmonary bypass: preoperatively (MBL-1), 15 min after initiation of cardiopulmonary bypass (CPB) (MBL-E), 30 min (MBL-2), 4 h (MBL-3), 12 h (MBL-4) and 24 h (MBL-5) post-CPB and at discharge from hospital (MBL-K). Alterations in serum MBL levels were calculated as a ratio of its serum level at subsequent time-points (MBL-2, -3, -4, -5) to the preoperative (MBL-1) value. Decreases in MBL and MBL-MASP complexes were observed in all samples, correlating with a decrease in C4 and increase in C4a, confirming activation of the lectin pathway. Changes in MBL levels between children with an uncomplicated postoperative course and those suffering from infection or low cardiac output syndrome did not differ significantly, but significant differences were observed between the SIRS and non-SIRS groups. Paediatric cardiac surgery with the use of cardiopulmonary bypass activates the complement system via the lectin pathway and the latter contributes to the development of the post-bypass systemic inflammatory response.

Essential role for the lectin pathway in collagen antibody-induced arthritis revealed through use of adenovirus programming complement inhibitor MAp44 expression.

Previous studies using mannose-binding lectin (MBL) and complement C4-deficient mice have suggested that the lectin pathway (LP) is not required for the development of inflammatory arthritis in the collagen Ab-induced arthritis (CAIA) model. MBL, ficolins and collectin-11 are key LP pattern recognition molecules that associate with three serine proteases-MASP-1, MASP-2, and MASP-3-and with two MBL-associated proteins designated sMAP and MBL-associated protein of 44kDA (MAp44). Recent studies have shown that MAp44, an alternatively spliced product of the MASP-1/3 gene, is a competitive inhibitor of the binding of the recognition molecules to all three MASPs. In these studies, we examined the effect of treatment of mice with adenovirus (Ad) programmed to express human MAp44 (AdhMAp44) on the development of CAIA. AdhMAp44 and Ad programming GFP (AdGFP) expression were injected i.p. in C57BL/6 wild type mice prior to the induction of CAIA. AdhMAp44 significantly reduced the clinical disease activity (CDA) score by 81% compared with mice injected with AdGFP. Similarly, histopathologic injury scores for inflammation, pannus, cartilage and bone damage, as well as C3 deposition in the cartilage and synovium, were significantly reduced by AdhMAp44 pretreatment. Mice treated with AdmMAp44, programming expression of mouse MAp44, also showed significantly decreased CDA score and histopathologic injury scores. In addition, administration of AdhMAp44 significantly diminished the severity of Ross River virus-induced arthritis, an LP-dependent model. Our study provides conclusive evidence that an intact complement LP is essential to initiate CAIA, and that MAp44 may be an appropriate treatment for inflammatory arthritis.

The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase.

The pathogenic bacterium Staphylococcus aureus actively evades many aspects of human innate immunity by expressing a series of small inhibitory proteins. A number of these proteins inhibit the complement system, which labels bacteria for phagocytosis and generates inflammatory chemoattractants. Although the majority of staphylococcal complement inhibitors act on the alternative pathway to block the amplification loop, only a few proteins act on the initial recognition cascades that constitute the classical pathway (CP) and lectin pathway (LP). We screened a collection of recombinant, secreted staphylococcal proteins to determine whether S. aureus produces other molecules that inhibit the CP and/or LP. Using this approach, we identified the extracellular adherence protein (Eap) as a potent, specific inhibitor of both the CP and LP. We found that Eap blocked CP/LP-dependent activation of C3, but not C4, and that Eap likewise inhibited deposition of C3b on the surface of S. aureus cells. In turn, this significantly diminished the extent of S. aureus opsonophagocytosis and killing by neutrophils. This combination of functional properties suggested that Eap acts specifically at the level of the CP/LP C3 convertase (C4b2a). Indeed, we demonstrated a direct, nanomolar-affinity interaction of Eap with C4b. Eap binding to C4b inhibited binding of both full-length C2 and its C2b fragment, which indicated that Eap disrupts formation of the CP/LP C3 proconvertase (C4b2). As a whole, our results demonstrate that S. aureus inhibits two initiation routes of complement by expression of the Eap protein, and thereby define a novel mechanism of immune evasion.

Low level of MAp44, an inhibitor of the lectin complement pathway, and long-term graft and patient survival; a cohort study of 382 kidney recipients.

BACKGROUND: Higher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient's native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation. METHODS: Two mannan-binding lectin (MBL) associated proteases, MASP-2 and MASP-3 (activators of the lectin pathway) and two MBL-associated proteins, MAp44 and MAp19 (inhibitors of the lectin pathway) were measured at the time of transplantation in 382 patients (≥17 years old) transplanted in 2000-2001. The cohort was followed until December 31, 2014. Data on patient and graft survival were obtained from the Norwegian Renal Registry. Cox proportional hazard regression models were performed for survival analyses. RESULTS: Low MAp44 level (1st versus 2-4 quartile) was significantly associated with overall mortality; HR 1.52, 95 % CI 1.08-2.14, p = 0.017. In the sub analyses in groups below and above median age (51.7 years), low MAp44 as a predictor of overall mortality was statistically significant only in recipients of ≤51.7 years; HR 2.57, 95 % CI 1.42-4.66, p = 0.002. Furthermore, low MAp44 was associated with mortality due to infectious diseases; HR 2.22, 95 % CI 1.11-4.41, p = 0.023. There was no association between MASP-2, MASP-3 or MAp19 levels and patient mortality. No association between any measured biomarkers and death censored graft loss was found. CONCLUSIONS: Low MAp44 level at the time of transplantation was associated with increased overall mortality in kidney recipients of median age of 51.7 years or below and with mortality due to infectious diseases in the whole patient cohort after nearly 14-years of follow up after transplantation. No associations between other effector molecules; MASP-2, MASP-3 or MAp19 and recipient mortality were found, as well as no association of any biomarker with death censored graft loss.

Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation.

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with high mortality rate due to progressive enlargement and eventual rupture. There is currently no established therapy known to alter the rate of aneurysmal expansion. Thus, understanding the processes that initiate and sustain aneurysmal growth is pivotal for the development of medical therapies aimed at halting disease progression. Using an elastase-induced AAA mouse model that recapitulates key features of human AAA, we previously reported that a natural IgG antibody directs alternative pathway complement activation and initiates the inflammatory process that culminates in aneurysmal development. The target of this natural antibody, however, was unknown. Herein we identify a natural IgG that binds to fibrinogen deposited in elastase-perfused aortic tissues, activates the complement lectin pathway (LP), and induces AAA. Moreover, we establish that alterations in the glycosylation patterns of this antibody critically affect its ability to activate the LP in vivo. We find that LP activation precedes the alternative pathway and absence of the LP complement protein mannan-binding lectin abrogates elastase-induced AAA. In human AAA tissues the mouse anti-fibrinogen antibody recognizes epitopes that localize to the same areas that stain positively for mannan-binding lectin, which suggests that the complement LP is engaged in humans as well. Lastly, we demonstrate that circulating antibodies in a subset of AAA patients react against fibrinogen or fibrinogen-associated epitopes in human aneurysmal tissues. Our findings support the concept that an autoimmune process directed at aortic wall self-antigens may play a central role in the immunopathogenesis of AAA.

Anti-C1q autoantibodies from systemic lupus erythematosus patients activate the complement system via both the classical and lectin pathways.

Autoantibodies against complement C1q (anti-C1q) strongly correlate with the occurrence of lupus nephritis and hypocomplementemia in systemic lupus erythematosus (SLE). Although a direct pathogenic role of anti-C1q has been suggested, the assumed complement-activating capacity remains to be elucidated. Using an ELISA-based assay, we found that anti-C1q activate the classical (CP) and lectin pathways (LP) depending on the anti-C1q immunoglobulin-class repertoire present in the patient's serum. IgG anti-C1q resulted in the activation of the CP as reflected by C4b deposition in the presence of purified C1 and C4 in a dose-dependent manner. The extent of C4b deposition correlated with anti-C1q levels in SLE patients but not in healthy controls. Our data indicate that SLE patient-derived anti-C1q can activate the CP and the LP but not the alternative pathway of complement. These findings are of importance for the understanding of the role of anti-C1q in SLE suggesting a direct link to hypocomplementemia.

Collectin liver 1 and collectin kidney 1 and other complement-associated pattern recognition molecules in systemic lupus erythematosus.

The objective of this study was to explore the involvement of collectin liver 1 (CL-L1) and collectin kidney 1 (CL-K1) and other pattern recognition molecules (PRMs) of the lectin pathway of the complement system in a cross-sectional cohort of systemic lupus erythematosus (SLE) patients. Concentrations in plasma of CL-L1, CL-K1, mannan-binding lectin (MBL), M-ficolin, H-ficolin and L-ficolin were determined in 58 patients with SLE and 65 healthy controls using time-resolved immunoflourometric assays. The SLE patients' demographic, diagnostic, clinical and biochemical data and collection of plasma samples were performed prospectively during 4 months. CL-L1, CL-K1 and M-ficolin plasma concentrations were lower in SLE patients than healthy controls (P-values < 0.001, 0.033 and < 0.001, respectively). H-ficolin concentration was higher in SLE patients (P < 0.0001). CL-L1 and CL-K1 plasma concentrations in the individuals correlated in both patients and controls. Patients with low complement component 3 (C3) demonstrated a negative correlation between C3 and CL-L1 and CL-K1 (P = 0.022 and 0.031, respectively). Patients positive for anti-dsDNA antibodies had lower levels of MBL in plasma than patients negative for anti-dsDNA antibodies (P = 0.02). In a cross-sectional cohort of SLE patients, we found differences in the plasma concentrations of CL-L1, CL-K1, M-ficolin and H-ficolin compared to a group of healthy controls. Alterations in plasma concentrations of the PRMs of the lectin pathway in SLE patients and associations to key elements of the disease support the hypothesis that the lectin pathway plays a role in the pathogenesis of SLE.