Plasma Mannose-binding Lectin Levels Research Articles

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and theirpolymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotypeDD was found to be associated with COVID-19 cases in the urban population of Patna city.

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19.

Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.

Local and Systemic Concentrations of Pattern Recognition Receptors of the Lectin Pathway of Complement in a Cohort of Patients With Interstitial Lung Diseases.

BackgroundThe role of the lectin pathway of complement in the pathogenesis of interstitial lung diseases (ILDs) is largely unknown. Pattern recognition receptors (PRR) of the lectin pathway are involved in the clearance of apoptotic cells either via activation of the complement system or as direct opsonins. As recent findings suggest a role of apoptosis in the development of pulmonary fibrosis, the influence of plasma lectins has lately been considered in various ILDs, but data on local concentrations in the lungs are lacking. This study investigated the role of mannose-binding lectin (MBL), ficolin-2 and ficolin-3 in ILD patients with a focus on idiopathic pulmonary fibrosis (IPF) and sarcoidosis.MethodsA case control study was conducted involving 80 patients with different forms of ILD as well as 40 control patients undergoing routine flexible bronchoscopy with bronchoalveolar lavage (BAL). Plasma and BAL fluid (BALF) levels of MBL, ficolin-2 and ficolin-3 as well as complement split products C4d and C5a (only in BALF) were measured by enzyme-linked immunosorbent assays. Eight single-nucleotide polymorphisms (SNPs) of MBL and ficolin-2 were determined by genotyping and tested for their association with ILDs.ResultsWe included 35, 35, 10, and 40 patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), other ILD, and a control group, respectively. BALF but not plasma levels of the three PRR were significantly elevated in sarcoidosis patients compared to a control group without ILD (MBL: median 66.8 vs. 24.6 ng/ml, p = 0.02, ficolin-2: 140 vs. 58.8 ng/ml, p = 0.01, ficolin-3: 2523 vs. 1180 ng/ml, p = 0.02), whereas the frequency of the investigated SNPs was similar. In line, complement split products were markedly elevated in BALF of sarcoidosis patients (C4d, median 97.4 vs. 0 ng/ml, p = 0.10; C5a, 23.9 vs. 9.1 ng/ml, p = 0.01). There was a weak positive correlation of BALF ficolin-3 with serum neopterin, a marker of sarcoidosis activity. In IPF patients, we observed numerically higher MBL plasma and BALF levels (plasma, median 1511 vs. 879 ng/ml, p = 0.44; BALF, 37.5 vs. 24.6 ng/ml, p = 0.7) as well as lower ficolin-2 plasma levels (plasma 1111 vs. 1647 ng/ml, p = 0.11). Ficolin-2 plasma levels were inversely correlated with the forced vital capacity (r = 0.55, p = 0.1).ConclusionThis is the first study to simultaneously assess systemic and local lectin pathway protein levels in ILD patients. Our data suggest an involvement of PRR of the lectin pathway in the pathogenesis of sarcoidosis given the significantly higher BALF levels compared to a control group. Additional analyses in a larger patient cohort are required to confirm or refute a potential effect of local and/or systemic ficolin-2 levels in IPF patients.

Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 Patients

The ongoing COVID-19 pandemic has caused significant morbidity and mortality worldwide, as well as profound effects on society. COVID-19 patients have an increased risk of thromboembolic (TE) complications, which develop despite pharmacological thromboprophylaxis. The mechanism behind COVID-19-associated coagulopathy remains unclear. Mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, has been suggested as a potential amplifier of blood coagulation during thromboinflammation. Here we describe data from a cohort of critically ill COVID-19 patients ( n = 65) treated at a tertiary hospital center intensive care unit (ICU). A subset of patients had strongly elevated MBL plasma levels, and activity upon ICU admission, and patients who developed symptomatic TE (14%) had significantly higher MBL levels than patients without TE. MBL was strongly correlated to plasma D-dimer levels, a marker of COVID-19 coagulopathy, but showed no relationship to degree of inflammation or other organ dysfunction. In conclusion, we have identified complement activation through the MBL pathway as a novel amplification mechanism that contributes to pathological thrombosis in critically ill COVID-19 patients. Pharmacological targeting of the MBL pathway could be a novel treatment option for thrombosis in COVID-19. Laboratory testing of MBL levels could be of value for identifying COVID-19 patients at risk for TE events.

No association of complement mannose-binding lectin deficiency with cardiovascular disease in patients with Systemic Lupus Erythematosus

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.

Plasma levels of mannose‐binding lectin and future risk of venous thromboembolism

BackgroundAnimal and observational studies have suggested a pathophysiological role for complement in venous thromboembolism (VTE), but the initiating mechanisms are unknown. Mannose‐binding lectin (MBL) bound to altered host cells leads to activation of the lectin complement pathway, and both high and low MBL levels have been implicated in the pathophysiology of cardiovascular disease. ObjectivesTo investigate the association between plasma MBL levels and future risk of incident VTE. MethodsWe conducted a nested case‐control study in 417 VTE patients and 849 age‐matched and sex‐matched controls derived from the general population (Tromsø Study). Plasma MBL levels were measured using enzyme‐linked immunosorbent assay. Logistic regression models were used to estimate odds ratio (OR) for VTE across quartiles of plasma MBL levels. ResultsSubjects with plasma MBL levels in the lowest quartile (<435 ng/mL) had a reduced OR for overall VTE (OR 0.79, 95% confidence interval [CI]: 0.56‐1.10) and for DVT (OR 0.70, 95% CI: 0.47‐1.04) compared to those with MBL in the highest quartile (≥2423 ng/mL) after multivariable adjustments. For VTE, DVT, and pulmonary embolism (PE) the ORs decreased substantially with decreasing time between blood sampling and VTE event. ConclusionsOur findings suggest that low plasma MBL levels are associated with reduced risk of VTE, and DVT in particular.

Changes in Mannose-Binding Lectin and Collectin Kidney 1 Levels in Sepsis Patients With and Without Disseminated Intravascular Coagulation.

In sepsis, systemic coagulation activation frequently causes disseminated intravascular coagulation (DIC), and the uncontrolled activation of the complement system can induce multiple organ dysfunction and poor prognosis. This study aimed to examine the association of DIC with levels of collectin kidney 1 (CL-K1), a novel collectin of the complement system, and mannose-binding lectin (MBL), a classical-type collectin in patients with sepsis. We collected blood samples prospectively from adult patients with sepsis admitted to the intensive care unit (ICU) from day 1 (admission) to day 5. The CL-K1 and MBL levels were measured by enzyme-linked immunosorbent assay, and DIC was diagnosed by using a scoring algorithm. The correlation of CL-K1 and MBL levels with other coagulation markers was analyzed. There were 37 patients with DIC (DIC group) and 15 without DIC (non-DIC group). Compared to the non-DIC group, the DIC group had more severe conditions and higher mortality. During the 5 days after ICU admission, plasma CL-K1 levels were similar between the groups, but plasma MBL levels were significantly lower in the DIC group. Plasma CL-K1 levels were weakly correlated with prothrombin time, activated partial thromboplastin time, and antithrombin levels; plasma MBL levels were weakly correlated with fibrin/fibrinogen degradation product levels and DIC score. In conclusion, during the first 5 days of ICU admission, plasma CL-K1 levels were similar between the DIC and non-DIC groups. However, plasma MBL levels were lower in the DIC group compared to the non-DIC group, and the significance of this difference grew gradually over time.

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients.

Background: Hemodialysis (HD) is a life-saving treatment for patients with end stage renal disease. However, HD patients have markedly increased rates of cardiovascular morbidity and mortality. Previously, a link between the complement system and cardiovascular events (CV-events) has been reported. In HD, systemic complement activation occurs due to blood-to-membrane interaction. We hypothesize that HD-induced complement activation together with inflammation and thrombosis are involved in the development of CV-events in these patients.Methods: HD patients were followed for the occurrence of CV-events during a maximum follow-up of 45 months. Plasma samples were collected from 55 patients at different time points during one HD session prior to follow-up. Plasma levels of mannose-binding lectin, properdin and C3d/C3 ratios were assessed by ELISA. In addition, levels of von Willebrand factor, TNF-α and IL-6/IL-10 ratios were determined. An ex-vivo model of HD was used to assess the effect of complement inhibition.Results: During median follow-up of 32 months, 17 participants developed CV-events. In the CV-event group, the C3d/C3-ratio sharply increased 30 min after the start of the HD session, while in the event-free group the ratio did not increase. In accordance, HD patients that developed a CV-event also had a sustained higher IL-6/IL-10-ratio during the first 60 min of the HD session, followed by a greater rise in TNF-α levels and von Willebrand factor at the end of the session. In the ex-vivo HD model, we found that complement activation contributed to the induction of TNF-α levels, IL-6/IL-10-ratio and levels of von Willebrand factor.Conclusions: In conclusion, these findings suggest that early intradialytic complement activation predominantly occurred in HD patients who develop a CV-event during follow-up. In addition, in these patients complement activation was accompanied by a pro-inflammatory and pro-thrombotic response. Experimental complement inhibition revealed that this reaction is secondary to complement activation. Therefore, our data suggests that HD-induced complement, inflammation and coagulation are involved in the increased CV risk of HD patients.

Mannose Binding Lectin and Pentraxin 3 in Patients with Diabetic Retinopathy

Mannose binding lectin (MBL) is a protein of the complement system and pentraxin-3 (PTX3) is an acute phase protein both with an important role in inflammatory diseases, such as diabetic retinopathy (DR). To evaluate whether plasma MBL and PTX3 levels are associated with the development of DR and if patients with and without DR can be distinguished. The patients were divided into three groups: diabetic without DR; with mild/moderate DR, and with severe/proliferative DR. PTX3 and MBL levels were measured with enzyme-linked immunosorbent assay kits. A total of 74 patients were included. A significant association was observed between high levels of MBL and severe DR; 47% of patients with severe/proliferative DR had high levels of MBL, whereas 12% of the patients with diabetes but no DR had high levels of MBL (p=0.008; odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.4-25.0). High levels of MBL were more frequent in patients with severe/proliferative disease (47%) when compared to those with mild/moderate DR (20%), p=0.04 (OR: 3.46; 95% CI: 1.0-11.8). PTX3 levels were similar among the groups and were not related to the development or severity of DR. We found a significant association between high plasma MBL levels and DR development as well as with severe/proliferative DR. We observed no relationship between plasma PTX3 levels and the development or severity of DR.

The association of mannose-binding lectin 2 polymorphisms with outcome in very low birth weight infants.

ObjectivesStudies on the influence of mannose-binding lectin (MBL) deficiency on infection susceptibility in preterm infants have yielded controversial results. We investigated the association of genotype-based MBL levels with outcome in very-low-birth weight infants (VLBWI).MethodsWe genotyped 3 genetic variants of MBL2 (rs1800450, rs1800451, rs5030737) in 6878 VLBWI. MBL plasma levels were categorized as normal (wild type, A/A), low (heterozygotes, A/O) or undetectable (homozygotes, O/O). Primary outcome was the effect of genotype-based MBL2 levels on blood-culture proven and clinical sepsis during primary stay in hospital. We also evaluated burden of infection within 24 months after discharge.ResultsWe found no association between MBL levels and sepsis risk in the whole cohort. Infants without measurable MBL levels born between 32 0/7 to 36 6/7 weeks of gestation, however, had a higher rate of Gram-negative sepsis than infants with normal or reduced MBL levels. In a follow-up investigation at 24 months (n = 1070 infants), infants without measurable MBL levels suffered more frequently from stomatitis and urinary tract infection.ConclusionsIn a large cohort of VLBWI MBL2 deficiency had no major impact on infection risk unless children were born between 32 0/7 and 36 6/7 weeks of gestation.

Mannose binding lectin polymorphisms in systemic lupus erythematosus in Spain

Low mannose binding lectin (MBL) producer genotypes have been considered as a systemic lupus erythematosus (SLE) risk factor. The aim of this study was to explore whether polymorphisms in the MBL gene are associated with susceptibility to SLE and disease-specific clinical manifestations or with disease severity in SLE patients in Son Llàtzer Hospital. MBL2 exon 1 and promoter polymorphisms were genotyped and MBL plasma levels were quantified by ELISA in 39 SLE cases and in 96 healthy controls. High MBL producer genotypes HYPA and LXPA were the most frequent haplotypes (65 and 62 participants, respectively). LYQC/HYPD, LXPA/LYQC and LYPB/HYPD were only found in SLE, and all of them were related to severe MBL deficiency. SLE patients showed a trend towards more severe MBL deficiency (MBL &lt;100 ng/mL) compared to controls (10 [25.6%] and 11 [11.46%] respectively, P = 0.07). The wild-type genotype was more frequent in controls compared to SLE. The trend towards more severe MBL deficiency in SLE and the fact that some of the low-MBL producer genotypes were only found in SLE patients, suggest that low MBL levels or MBL2 variant could be a risk factor for the development of SLE.

Second-trimester plasma mannose-binding lectin levels and risk of preterm birth

Objective: To investigate whether mannose-binding lectin (MBL) gene polymorphisms and low levels of second-trimester plasma MBL were significant risk factors for preterm birth in Taiwanese women.Methods: We conducted a prospective longitudinal study to explore the associations of MBL2 gene single nucleotide polymorphisms and plasma MBL levels between preterm birth and term controls. Blood samples were collected at 16–23 weeks of gestation, and were divided into 51 mothers with preterm births and 255 term controls after delivery. Blood samples were further collected at delivery from 11 mothers with term delivery and 9 with preterm births. DNA was isolated, and polymorphisms in exon 1, the promoter untranslated regions of MBL2 were determined by polymerase chain reaction. The plasma concentrations of MBL were measured by enzyme-linked immunosorbent assay.Results: There is a positive correlation between SNP genotypes and second-trimester plasma MBL levels. Among mothers with preterm births, a higher frequency of specific genotypes with low MBL levels was not observed. The second-trimester plasma MBL levels were not significantly different between mothers with preterm births (N = 51) and term deliveries (N = 255). However, among mothers (N = 11) with term pregnancies, the MBL plasma level significantly increased from the second trimester to delivery, whereas in mothers (N = 9) who developed preterm delivery, the MBL level did not significantly change.Conclusion: Genotypes associated with low levels of plasma MBL during pregnancy did not increase the risk of preterm births. A low second-trimester plasma MBL level is therefore not a predictor for the development of preterm birth.

Mannose-Binding Lectin Serum Levels in Patients With Candiduria.

Background:Candida species are normal mycoflora of human body which are capable to cause urinary tract infection (UTI). Mannose-binding lectin (MBL) is a kind of innate immune system and decreasing plasma levels of MBL may disrupt the natural immune response and increase susceptibility to infections.Objectives:The aim of the present study was to assess MBL in the serum of patients with candiduria and compare them with control.Patients and Methods:The blood and urine samples were collected from 335 patients (hospitalized in Golestan hospital, Ahvaz) using standard methods and the growing colonies on CHROMagar were identified using routine diagnostic tests. MBL activity in the serum of 45 patients with candiduria and 45 controls was measured using Eastbiopharm enzyme-linked immunosorbent assay (ELISA) kit.Results:In this study, 45 (13.4 %) urine samples were positive for Candida species (17 males and 28 females). The most common isolated yeast was Candida albicans (34%), followed by C. glabrata (32.1%), C. tropicalis (9.4%), other Candida species (22.6%), and Rhodotorula species (1.9%). The mean serum levels of MBL were 0.85 ± 0.01 ng/mL and 1.02 ± 0.03 ng/mL among candiduric patients and controls, respectively, and there was no significant difference between the two groups (P = 0.6).Conclusions:Our results showed that there was no significant relationship between MBL serum levels and candiduria.

HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe: Is There an Effect of the Mannose Binding Lectin Deficiency?

HIV infection remains a major global health burden since its discovery in 1983. Sub-Saharan Africa is the region hardest hit by the HIV/AIDS pandemic where 63% of the 33 million infected people live. While there is marked person-to-person variability in susceptibility, progression, and survival with HIV infection, there is a paucity of predictive diagnostics associated with these clinical endpoints. In this regard, the deficiency in plasma Mannose Binding Lectin (MBL) is a common opsonic defect reported to increase susceptibility infections, including HIV. To the best of our knowledge, we report here the first study on the putative role of MBL deficiency on HIV progression and survival in an African adult population. We hypothesized that MBL deficiency has a role to play in HIV infection by increasing HIV disease progression and decreasing survival. We assessed the role of MBL deficiency on HIV disease progression and survival in a Zimbabwean adult population enrolled in the Mupfure Schistosomiasis and HIV (MUSH) cohort. We analyzed blood samples for MBL levels, MBL2 genotypes, HIV-1 status, viral load, and CD4(+) T cell counts. Participants were followed for 3 years wherein the endpoints were measured at baseline, 6 weeks, and 3, 6, 12, 24, and 36 months. Disease progression was measured as the rate of decline in CD4(+) T cell counts and the rate of increase in HIV viral load. We assessed 197 HIV positive adults where 83% (164) were women with a median age of 31 years. Prevalence of plasma MBL deficiency (less than 100 μg/L) and MBL2 deficient genetic variants (A/O and O/O genotypes) was 21% (42 out of 197) and 39% (74 out of 190), respectively. We did not observe a significant role to explain individual variation in mortality, change of CD4(+) T cell count, and viral load by MBL plasma deficiency or MBL2 genetic variants from baseline to 3 years follow up period in this adult population. We suggest the need for global OMICS research and that the present findings attest to the large between-population variability in a host of factors that can predispose individuals susceptible to HIV progression and mortality. We therefore cannot recommend at this time the use of plasma MBL levels or MBL2 genetic variants as a prognostic marker in HIV infection, disease progression, and survival in this adult population in Africa.

Effects of a phytogenic feed additive on growth performance, susceptibility of channel catfish to Edwardsiella ictaluri and levels of mannose binding lectin

A study was conducted to investigate the effect of a phytogenic feed additive (Digestarom® P.E.P. MGE; containing the essential oils carvacrol, thymol, anethol, and limonene) on growth performance and disease susceptibility to Edwardsiella ictaluri. Two hundred and fifty juvenile channel catfish, Ictalurus punctatus (7.2 ± 0.1 g) were allotted into the following treatments: Control (floating diet) and EO (floating diet supplemented with essential oils). The fish were fed their respective diets for 6 weeks. At the end of the study, all fish were exposed to virulent E. ictaluri by bath immersion (1.9 × 107 cfu/mL; final concentration). Plasma and tissue samples were taken to quantify protein and mRNA expression levels of mannose binding lectin (MBL). Weight gain and food conversion ratio were similar between treatments. After exposing fish to virulent E. ictaluri and monitoring mortality for 21 days, survival was 43% higher (69.5 vs 48.4%) in fish fed EO compared to fish not treated with EO (P < 0.05). One day after challenge, plasma MBL levels were down-regulated in the non-treated fish compared to non-challenged fish. In the EO fish, MBL levels were similar to non-challenged fish but significantly higher than non-treated fed fish (P < 0.001). By d 7, plasma MBL levels increased in non-treated fed fish to levels observed in the EO and non-challenged fish. On d 14, MBL mRNA levels were upregulated 15-fold in fish fed EO compared to non-treated fed fish and non-challenged fish (P < 0.001). The results demonstrate that essential oils improved survival of channel catfish challenged with E. ictaluri. Mechanisms through which essential oils improve survival may involve MBL.

Age-dependent association of mannose-binding lectin polymorphisms with the development of pulmonary tuberculosis in Viet Nam

Mannose-binding lectin (MBL) binds to pathogens and induces complement-mediated opsonophagocytosis. Although the association between MBL2 polymorphisms and tuberculosis (TB) has been studied in various populations, the results are controversial. We explored the stages of TB associated with MBL2 polymorphisms. X/Y (rs7096206) and A/B (rs1800450) were genotyped in 765 new patients with active pulmonary TB without HIV infection and 556 controls in Hanoi, Viet Nam. The MBL2 nucleotide sequences were further analyzed, and plasma MBL levels were measured in 109 apparently healthy healthcare workers and 65 patients with TB. Latent TB infection (LTBI) was detected by interferon-gamma release assay (IGRA). The YA/YA diplotype, which exhibited high plasma MBL levels, was associated with protection against active TB in younger patients (mean age=32)≦45years old (odds ratio, 0.61; 95% confidence interval, 0.46–0.80). The resistant diplotype was less frequently found in the younger patients at diagnosis (P=0.0021). MBL2 diplotype frequencies and plasma MBL levels were not significantly different between the IGRA-positive and -negative groups. MBL2 YA/YA exhibited a protective role against the development of TB in younger patients, whereas the MBL2 genotype and MBL levels were not associated with LTBI. High MBL levels may protect against the early development of pulmonary TB after infection.

Mannose binding lectin genotypes are not associated with increased risk of unexplained recurrent pregnancy loss

Immune response to infections has been associated with recurrent pregnancy loss (RPL). Low plasma mannose binding lectin (MBL) levels, an innate immunity factor in infections, has been related to RPL. In this study, we tested the hypothesis that MBL genotypes that are known to cause reduced plasma MBL levels are significantly more frequent among women experiencing unexplained RPL. This study included 219 Caucasian women diagnosed with unexplained RPL and 236 control women. All participants were genotyped for two promoter (-550 C > G and -221 G > C) and three missense (R52C, G54D and G57E) mutations in exon 1. These mutations are known to be associated with variations in plasma MBL levels. Genotype frequencies were estimated by gene counting and were compared to the expectation of Hardy-Weinberg equilibrium by chi-squared (X(2)) analysis and Fisher's exact test. Allele and genotype frequencies were compared in cases and controls using X(2) contingency table analysis. There was no difference in demographics between cases and controls. The number of miscarriages in the participants with RPL ranged from 2 to 10 spontaneous abortions (SAB's) per participant. Populations genotyped were in Hardy-Weinberg equilibrium. There was no association between a history of RPL and multi-SNP genotypes at the MBL locus. In unexplained RPL, the number of SAB's and live birth rates were unaffected by MBL genotype. There was no association between MBL genotype and the risk of unexplained RPL. The occurrence of live birth was not associated with MBL genotype. Genotypes known to cause low MBL plasma levels are not associated with an increased risk of unexplained RPL.

Spleen Index and Mannose‐Binding Lectin Levels in Four Channel Catfish Families Exhibiting Different Susceptibilities to Flavobacterium columnare and Edwardsiella ictaluri

Edwardsiella ictaluri and Flavobacterium columnare are two bacterial pathogens that affect channel catfish Ictalurus punctatus aquaculture. At the Catfish Genetics Research Unit (U.S. Department of Agriculture, Agricultural Research Service), some progress has been made in selectively breeding for resistance to E. ictaluri; however, the susceptibility of these families to F. columnare is not known. Our objectives were to obtain baseline information on the susceptibility of channel catfish families (maintained as part of the selective breeding program) to E. ictaluri and F. columnare and to determine whether the spleen index and plasma levels of mannose-binding lectin (MBL) are predictive indicators of susceptibility to these pathogens. Four channel catfish families were used: family A was randomly chosen from spawns of fish that were not selectively bred for resistance; families B, C, and D were obtained after selection for resistance to E. ictaluri. All four families were immersion challenged with both bacterial pathogens; the spleen index and plasma MBL levels of unchallenged fish from each family were determined. Mean cumulative percent mortality (CPM) after E. ictaluri challenge ranged from 4% to 33% among families. Families A and B were more susceptible to F. columnare (mean CPM of three independent challenges = 95% and 93%) than families C and D (45% and 48%), demonstrating that there is genetic variation in resistance to F. columnare. Spleen index values and MBL levels were not significantly different, indicating that these metrics are not predictive indicators of F. columnare or E. ictaluri susceptibility in the four tested families. Interestingly, the two families that exhibited the highest CPM after F. columnare challenges had the lowest CPM after E. ictaluri challenge. Further research on larger numbers of families is needed to determine whether there is any genetic correlation between resistance to E. ictaluri and resistance to F. columnare.

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

BackgroundLong-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS). Mannose binding lectin (MBL) belongs to the innate immune system, participates in complement activation, and may predispose to graft rejection. We investigated mannose binding (MBL) during cold ischemia and in tissue samples from explanted lungs with BOS, and assessed MBL and complement proteins in plasma post-lung transplantation relative to BOS staging.MethodsMBL was detected by immunohistochemistry lung tissue at the time of cold ischemia and in samples with BOS. MBL was assayed in the peripheral blood of 66 lung transplant patients transplanted between 1990–2007.ResultsMBL localized to vasculature and basement membrane during cold ischemia and BOS. Patients further out post-lung transplant > 5 years (n = 33), had significantly lower levels of MBL in the blood compared to lung transplant patients < 5 years with BOS Op-3 (n = 17), 1738 ± 250 ng/ml vs 3198 ± 370 ng/ml, p = 0.027, and similar levels to lung transplant patients < 5 years with BOS 0 (n = 16), 1738 ± 250 ng/ml vs 1808 ± 345 ng/ml. MBL levels in all BOS 0 (n = 30) vs. all BOS Op-3 (n = 36) were 1378 ± 275 ng/ml vs. 2578 ± 390 ng/ml, p = 0.001, respectively. C3 plasma levels in BOS 0 (n = 30) vs. BOS Op-3 (n = 36) were 101 ± 19.8 mg/ml vs. 114 ± 25.2 mg/ml, p = 0.024, respectively.ConclusionsMBL localizes within the lung during graft ischemia and BOS, higher levels of plasma MBL are associated with BOS Op-3 and < 5 years post-transplant, and higher level of plasma complement protein C3 was associated with BOS Op-3 clinical status. MBL may serve as a biomarker for poorer outcome post-lung transplantation.