scholarly journals Complement Activation Is Associated With Crescents in IgA Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zi Wang ◽  
Xinfang Xie ◽  
Jingyi Li ◽  
Xue Zhang ◽  
Jiawei He ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Complement Activation ◽  
Predictive Ability ◽  
Roc Curves ◽  
Rapid Progression ◽  
Crescent Formation ◽  
Potential Biomarker ◽  
Mannose Binding ◽  
Progression Of Kidney Disease ◽  
Binding Lectin

IntroductionCrescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.MethodsOne hundred IgAN patients with various proportions of crescents—24 with 1%–24%, 27 with 25%–49%, 21 with 50%–74% 12 with more than 75%, and 16 without crescents—were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.ResultsIgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652–62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0–1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127–66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859–2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058–1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916–11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.ConclusionExcess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.

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

2020 ◽  
Vol 120 (12) ◽  
pp. 1720-1724 ◽  
Author(s):  
Michael Hultström ◽  
Robert Frithiof ◽  
Oskar Eriksson ◽  
Barbro Persson ◽  
Miklos Lipcsey ◽  
...  
Keyword(s):  
Critically Ill ◽  
Complement Activation ◽  
Tertiary Hospital ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
Strongly Correlated ◽  
Increased Risk ◽  
Mannose Binding ◽  
Patients At Risk ◽  
Binding Lectin

AbstractThe 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.

scholarly journals Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

mBio ◽  
2011 ◽  
Vol 2 (6) ◽  
Author(s):  
Panisadee Avirutnan ◽  
Richard E. Hauhart ◽  
Mary A. Marovich ◽  
Peter Garred ◽  
John P. Atkinson ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Human Serum ◽  
Complement Activation ◽  
Insect Cell ◽  
Denv Infection ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
Denv Serotypes ◽  
Mannose Binding ◽  
Binding Lectin

ABSTRACTMannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis.IMPORTANCEDengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Moreover, we observed a direct correlation with the concentration of MBL in human serum and neutralization of DENV infection. Our studies suggest that common genetic polymorphisms that result in disparate levels and function of MBL in humans may impact DENV infection, pathogenesis, and disease severity.

scholarly journals Secondary Cell Wall Polymers ofEnterococcus faecalisAre Critical for Resistance to Complement Activation via Mannose-binding Lectin

2012 ◽  
Vol 287 (45) ◽  
pp. 37769-37777 ◽  
Author(s):  
Stefan Geiss-Liebisch ◽  
Suzan H. M. Rooijakkers ◽  
Agnieszka Beczala ◽  
Patricia Sanchez-Carballo ◽  
Karolina Kruszynska ◽  
...  
Keyword(s):  
Cell Wall ◽  
Complement Activation ◽  
Secondary Cell Wall ◽  
Mannose Binding Lectin ◽  
Cell Wall Polymers ◽  
Mannose Binding ◽  
Binding Lectin

Mannose Binding Lectin: A Potential Biomarker for Many Human Diseases

2016 ◽  
Vol 23 (33) ◽  
pp. 3847-3860 ◽  
Author(s):  
Senjam Sunil Singh ◽  
Randy Chi Fai Cheung ◽  
Jack Ho Wong ◽  
Tzi Bun Ng
Keyword(s):  
Mannose Binding Lectin ◽  
Human Diseases ◽  
Potential Biomarker ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Human Mannose-binding Lectin in Immunity

2004 ◽  
Vol 199 (10) ◽  
pp. 1295-1299 ◽  
Author(s):  
Jean-Laurent Casanova ◽  
Laurent Abel
Keyword(s):  
Complement Activation ◽  
Prospective Studies ◽  
Protective Immunity ◽  
Mannose Binding Lectin ◽  
Counter Selection ◽  
Wide Range ◽  
Mannose Binding ◽  
Severe Infections ◽  
Binding Lectin

Human mannose-binding lectin (MBL) recognizes a wide range of microorganisms and triggers the most ancient pathway of complement activation. However, ∼5% of individuals lack functional serum MBL and have not been found to be prone to severe infections in prospective studies. These data suggest that human MBL is largely redundant for protective immunity and may even have been subject to counter selection because of a deleterious impact.

scholarly journals Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin

2009 ◽  
Vol 297 (5) ◽  
pp. H1853-H1859 ◽  
Author(s):  
Marc N. Busche ◽  
Vasile Pavlov ◽  
Kazue Takahashi ◽  
Gregory L. Stahl
Keyword(s):  
Myocardial Ischemia ◽  
Complement Activation ◽  
Tissue Injury ◽  
Left Ventricular ◽  
Mannose Binding Lectin ◽  
Left Ventricular Ejection ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Mannose Binding ◽  
Binding Lectin

Complement activation has been shown to play an important role in the inflammation and tissue injury following myocardial ischemia and reperfusion (MI/R). Several recent studies from our laboratory demonstrated the importance of mannose-binding lectin (MBL) as the initiation pathway for complement activation and the resulting pathological effects following MI/R. However, other studies from the past suggest an important role of the classical pathway and perhaps natural antibodies. In the present study, we used newly generated genetically modified mice that lack secreted IgM (sIgM), MBL-A, and MBL-C (sIgM/MBL null) in a plasma reconstitution mouse model of MI/R. Following 30 min of ischemia and 4 h of reperfusion, left ventricular ejection fractions were significantly higher in sIgM/MBL null mice reconstituted with MBL null or sIgM/MBL null plasma compared with reconstitution with wild-type (WT) plasma or WT mice reconstituted with WT plasma following MI/R. Serum troponin I concentration, myocardial polymorphonuclear leukocyte infiltration, and C3 deposition were dependent on the combined presence of sIgM and MBL. These results demonstrate that MI/R-induced complement activation, inflammation, and subsequent tissue injury require both IgM and MBL. Thus MBL-dependent activation of the lectin pathway may not be completely antibody independent in I/R models.

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