Mannose-binding lectin: ancient molecule, interesting future.

Five hundred sixty-five million years ago, when the world was empty and barren because animal life had not colonized land yet, a common ancestor that we share with sea squirts (Ascidians) inhabited the seas. One of the genes that we still share with sea squirts today is a gene for mannose-binding lectin (MBL), signifying that this gene has existed for 1565 million years [1, 2] and, thus, has been highly conserved throughout animal evolution. Surely, this must indicate that MBL, the molecule encoded by the gene MBL2 in humans, is crucial for survival of all kinds of species; otherwise, the gene would have quickly been lost as a result of natural selection. But do humans really need it? There is a large body of data that indicate that low serum MBL concentration or MBL2-variant alleles that confer to low serum concentration are associated with an increased risk of infectious diseases, a more severe course of infection, and an increased risk of autoimmune diseases, cardiovascular diseases, and cancer. Conversely, a large population-based prospective study of MBL deficiency in 19000 adults from Scandinavia failed to reveal an effect of MBL deficiency on the morbidity and mortality associated with infectious diseases [3]. Moreover, recent evolutionary evidence indicates that the high worldwide prevalence of MBL2 deficiency or low-producing alleles is caused exclusively by human migration and genetic drift, indicating that MBL2 variation does not have strong effects on population fitness [4]. These findings suggest that MBL is largely redundant in innate defence against infection and that the effects of MBL on susceptibility to or the course of infectious diseases are small, evident only in combination with other immunodeficiencies, or merely present in the context of specific or rare infections. Consequently, studies that address the role of MBL in infectious diseases should either include large groups or focus on patients with specific conditions. Unfortunately, few studies of MBL have been performed with a large sample size; therefore, conflicting results have been reported. In this issue of Clinical Infectious Diseases , Eisen et al. [5] present a reanalysis of risk of death due to MBL deficiency from 6 previous studies with a total of 477 patients who had diverse infections, ranging from well-defined pneumococcal disease to undefined intensive care unit–ac-quired septic shock. The authors defined MBL deficiency as a serum MBL concentration !0.5 mg/mL; this cutoff value was based on reassessment of data from 4 studies …