Mannose-binding lectin gene polymorphism in brucellosis

Innate and adaptive immune systems have important roles in the response to the infections. Innate immunity constitutes the first line of the organism defense against infections. The innate immune system involves peripheral blood neutrophils, mononuclear phagocytes, epithelial barriers, natural killer (NK) cells, and some proteins that can recognize the infectious agents--the pathogens. The complement system, which is a member of the innate immune system, is activated by three main pathways: classic, alternative, and lectin pathways. The activation of the lectin pathway leads to three important biological effects as the opsonization and phagocytosis, and the lysis of the microorganisms, and the inflammation ultimately occurred. The lectin pathway starts with mannose-binding lectin (MBL, mannan-binding lectin or mannose-binding protein) or ficolin binding to the sugar groups on the surface of many microorganisms. As a part of the acute phase response, MBL is one of the complement system proteins, which is synthesized in the liver and released into blood. Mannose-binding lectin, independent from the antibody activation, acts as an opsonin since it ensures the phagocytosis of the microorganisms by the macrophages by specifically binding to N-acetyl-D-glucosamine, mannose, N-acetylmannosamine, L-fructose, and glucose on the surfaces of many pathogens such as yeasts, fungi, bacteria, and viruses. These sugars binding MBL are mostly present in mammalian cells . MBL activates the phagocytosis of the microorganisms and the complement system in the classic pathway, ensuring the lysis of the microorganisms. The present study aims to evaluate the correlation of gene MBL codon 54 polymorphism with the serum level of MBL in a healthy control group and a group of patients with or without complications, who are diagnosed with brucellosis; to investigate the association between the development of brucellosis with mutation and the occurrence of complications; and to compare the pre- and post-treatment serum levels of MBL in the group of patients diagnosed with brucellosis. The study will be conducted at the laboratories of Department of Infectious Diseases and Clinical Microbiology, Department of Medical Genetics and Department of Medical Biochemistry, Faculty of Medicine, Fırat University. The present study included a total of 40 patients, 20 of whom have been diagnosed with brucellosis, who do not have any complications (cardiovascular, osteoarticular, genitourinary, etc...), and have not received any treatment; and 20 of whom have been diagnosed with brucellosis and have complications. The control group composed of 50 healthy subjects. While the mean serum MBL levels in patients with brucellosis was 446.25±171.37 ng/ml before treatment, it was 544.40±195.58 ng/ml after treatment and it was found as 688.25±175.41 ng/ml in the control group (p<0.05). There was no significant difference in terms of pre-treatment MBL levels between the patients in which complication developed and the patients without complication. It was found that MBL levels after treatment have significantly increased in all patient groups when compared with the pre-treatment values. No significant difference was observed in after treatment levels in the control group. When the frequency of the MBL gene codon 54 polymorphism was compared in 40 cases; AA genotype was found in 30 patients (75%), AB genotype was found in seven patients (17.5%) and BB genotype was found in three patients (7.5%). Whereas, in the control group, BB genotype was detected in two patients (4%), AA genotype was detected in 39 patients (78%) and AB genotype was detected in nine patients (18%). There was no statistically significant difference between the patient group and the control group in terms of variant allele (AB / BB) prevalence (p = 0.450, OR = 0.98, 95%CI (0.33 – 2.92) ). As a result of the current study, no significant correlation was detected between the MBL codon 54 mutation and a predisposition to brucellosis or the development of complications. A significant correlation was detected between serum MBL levels and brucellosis disease and no correlation was detected between complication development and MBL levels.