Significantly increased levels of mannose-binding lectin (MBL) in rheumatic heart disease: a beneficial role for MBL deficiency

Abstract

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.

High levels of serum mannose-binding lectin are associated with the severity of clinical signs of leptospirosis

“…The MBL concentration obtained for the control group in this study was similar to those reported by other studies of the Brazilian population (12,13). The frequency of MBL levels <100 ng/mL in the control group was, however, very low (2%) compared to the genotypic frequency of MBL polymorphisms (6%) reported for a group of individuals with the same ethnic background (14).…”

Association of a new mannose-binding lectin variant with severe malaria in Gabonese children

“…Alternatively, the MBL2*HA diplotype and/or high plasma concentrations of MBL multimers have been associated with protection to some of these diseases, 14,23,24 but to predispose to and/ or to increase the severity of leprosy, tuberculosis, 21,25 visceral leishmaniasis, 26 sporadic ulcerative colitis 27 and rheumatic heart disease. 28 A total of 96% of the variation in the plasma levels of MBL multimers can be explained by genetic polymorphisms. 29 There may be 10-fold variation in MBL levels within one recognized haplotype and more polymorphic variants influencing the phenotype are to be expected.…”

Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia

“…Therefore, it could be hypothesized that fever in (most) patients with neutropenia is induced by the neutropenic state as such, rather than by the presence of infectious pathogens. This might explain why patients with high MBL genotypes had a higher incidence of febrile neutropenia in our study, because higher MBL levels might induce the occurrence of an immunological response [46]. Another explanation for our findings is that transient neutropenia is commonly associated with subclinical infections.…”

“…They showed that high MBL levels may be less beneficial for patients, possibly as a result of greater complement activation and the stimulation of proinflammatory signals [46], and that moderate MBL deficiency may be favorable, especially in patients who briefly receive immunosuppressive chemotherapy. This could explain why we only found an effect of promoter polymorphisms, which are known to have a less dramatic effect on MBL levels than exon polymorphisms, on the incidence of febrile neutropenia [18].…”