Although mannose-binding lectin (MBL) is known to be involved in the primary defense against microorganisms, there are emerging lines of evidence for an active proinflammatory role for MBL in different chronic diseases. In this study we determined the circulating levels of MBL in patients with rheumatic heart disease (RHD). A total of 100 patients (77 women, 23 men; mean age 45.8 +/- 11 years, range 19-76 years) with chronic RHD, and a previous diagnosis of rheumatic fever, were studied. Transthoracic echocardiography was performed in all patients to evaluate valvular heart disease. Ninety-nine healthy individuals matched for age, sex and ethnic origin were included as controls. MBL concentration was measured by enzyme-linked immunosorbent assay and C3 and C4 levels by turbidimetry. MBL levels were significantly higher in patients with RHD than in healthy subjects (mean +/- SEM: 3036.2 +/- 298.9 ng/ml versus 1942.6 +/- 185.5 ng/ml, P <0.003). In addition, MBL deficiency was more prevalent in controls (17.1%) than in patients (9% P <0.09). Concentrations of C4 were within the normal range (22.7 +/- 0.8 mg/dl, normal: 10.0-40.0 mg/dl), while C3 concentrations were found to be elevated (109.2 +/- 3.6 mg/dl, normal: 50.0-90.0 mg/dl). No correlation was observed between serum MBL levels and valve area or the type of surgical procedure. The significantly elevated circulating MBL levels in patients with RHD together with the greater prevalence of MBL deficiency in controls suggest that MBL may cause undesirable complement activation contributing to the pathogenesis of RHD.

SummaryFicolins are pattern-recognition proteins involved in innate immunity, which upon binding to their specific pathogen-associated molecular patterns on the microbial surfaces trigger the immune response either by binding to collectin cellular receptors or by initiating the complement lectin pathway. In humans, three ficolin genes have been identified, which encode ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin or Hakata antigen). Ficolin-2 was shown to bind to lipoteichoic acid, a cell wall constituent in all Gram-positive bacteria such as Streptococcus pyogenes, which is the aetiological agent of rheumatic fever (RF) and its most severe sequelae, chronic rheumatic heart disease (CRHD). Here we investigated polymorphisms in the promoter region of the FCN2 gene (at positions -986/-602 and +4) in 122 patients with RF and CRHD and in 210 healthy subjects from the same geographic region and socioeconomic background. The haplotype -986/-602/-4 G/G/A, which is related to low levels of L-ficolin, was observed more frequently in the CRHD group when compared to the healthy subjects [99/162, 61·1% versus 211/420, 50·2%, odds ratio (OR) 1·6, confidence interval (CI) 95% 1·1-2·3, P = 0·021]. The haplotype -986/-602/-4 A/G/A was observed more frequently in the healthy group when compared to the affected (RF plus CRHD) subjects (31/420, 7·4% versus 6/244, 2·5%, OR 3·2, CI 95% 0·13-0·77, P = 0·008). Based on those findings, one can conclude that polymorphisms associated with low levels of L-ficolin level may predispose an individual to recurrent and/or more severe streptococcal infection.

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