Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of the past two decennia, a 3rd route of complement activation (next to the classical and the alternative routes) has been identified: the lectin route in which mannose-binding lectin (MBL) plays an essential role. MBL is produced in the liver. From the phylogenetic and functional points of view, complement activation via MBL falls in between the alternative and the classical routes and combines the advantages of the former (an early response, without the intervention of antibodies) with those of the latter (high specificity). The binding of MBL to the surface of a microorganism results in the activation of two serine proteases (MASP1 and MASP2) that are coupled to MBL. These enzymes can activate C4 and C2 so that, via the MBL route, the C3-convertase of the classical route (C4b2b) is produced long before there are any specific antibodies. The gene for MBL is located on the long arm of chromosome 10 and consists of a promoter gene and 4 exons coding for the protein. The prevalence of mutations in the MBL gene is about 10%, but in Africa South of the Sahara it is as high as 30%. MBL deficiency predisposes both children and adults to all sorts of infectious diseases, chronic diarrhoea, tonsillitis, otitis media, pneumonia, (meningococcal) meningitis, sepsis and osteomyelitis. Remarkably, MBL deficiency may actually be advantageous in some infections, because certain microorganisms use MBL or complement to invade the cell.
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PMID:[Immunology in the medical practice. XXVII. Mannose-binding lectin, an important link for nonspecific or hereditary immune reaction]. 1107 14

The ficolins and mannose-binding lectin (MBL) create complexes with three different serine proteases (MASP-1, MASP-2 and MASP-3) and a truncated non-enzymatic form of MASP-2 (sMAP). MASP-2 is able to activate complement by cleavage of C4 and C2, while the physiological functions of MASP-1, MASP-3 and sMAP still are debated. MASP-1 and MASP-3 are alternative spliced forms of the same MASP gene. To gain insight in the molecular variation in the MASP-1/3 gene, we undertook a systematic study of the protein coding sequences of the MASP-1/3 gene. The coding regions of the MASP-1/3 gene were sequenced in 92 healthy Caucasian donors. A total of six nucleotide substitutions were detected. Five were detected only once. One polymorphism identified in exon 10 at position +50074 (rs 38343199) relative to the transcription start site resulting in the amino acid substitution of a glycine (GGG) with a glutamic acid residue (GAG) in the second complement control protein domain was observed. The frequency of this allele in 305 blood donors, 90 patients with systemic lupus erythematosus and 234 patients with the systemic inflammatory response syndrome (SIRS) and/or sepsis was 0.03, 0.017 and 0.03 respectively. No significant differences in genotype frequencies between the groups were observed (P > 0.45). However, the SIRS/sepsis group deviated from the Hardy-Weinberg expectations due to one variant allele homozygote (P = 0.07), which was not observed in the other groups. In conclusion, the MASP1/3 gene harbours a low-frequent polymorphic site resulting in an amino acid substitution, which may influence the function of the gene product.
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PMID:A novel mannose-binding lectin-associated serine protease 1/3 gene variant. 1744 53

Infections are a major cause of childhood mortality. We investigated components of the lectin pathway of complement activation in the context of sepsis at both genetic and protein levels in neonates, infants and older children. Major components of the lectin pathway and two genes for Toll-like receptors were studied in 87 neonates with confirmed sepsis and compared with 40 babies with infections who did not develop sepsis (disease controls) and 273 infection-free neonatal controls. A second cohort comprised 47 older children with sepsis and 87 controls. Low MBL-conferring genotypes (LXA/O+O/O) were more frequent in sepsis patients than in healthy controls but no significant differences in the frequency of SNPs of other lectin pathway genes (FCN1, FCN2, FCN3, MASP1/3, MASP2) or TLR receptor genes (TLR2, TLR4) were found. One case of primary MASP-2 deficiency was found among healthy pre-terms and one neonate suffering from SIRS was heterozygous for the rare FCN1 gene mutation, +6658 G>A. Generally, sepsis was associated with low serum MBL and low ficolin-2 concentrations on admission. Among neonates, ficolin-1 and MASP-2 levels were elevated in sepsis relative to healthy, but not disease, controls. Unlike neonates, ficolin-3 and MASP-2 levels were lower in older patients than in healthy controls while no difference was found for ficolin-1. With the possible exception of MBL, inherited lectin pathway insufficiencies do not seem to predispose to sepsis, rather changes in protein concentrations reflect alterations in disease course.
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PMID:Components of the lectin pathway of complement activation in paediatric patients of intensive care units. 2685 Mar 22