Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients

Perazzio, Sandro Félix; Silva, Neusa Pereira da; Carneiro‐Sampaio, Magda; Andrade, Luís Eduardo Coelho

doi:10.1016/j.rbre.2016.01.002

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…From a physiological and clinical point of view, the optimal cut-off value for low p-MBL levels still has to be determined: either across diseases or solely concerning RPL patients. In Danish laboratories, a p-MBL level ≤500 µg/l is defined as insufficient, and this is in agreement with the cut-off value used in previous studies investigating the impact of p-MBL levels in diseases such as severe acute respiratory syndrome coronavirus infection, chronic obstructive lung disease, systemic lupus erythematosus (SLE) and lupus nephritis ( Ip et al , 2005 ; Eagan et al , 2010 ; Albert et al , 2012 ; Perazzio et al , 2016 ). The optimal cut-off value probably varies between diseases but may also depend on the applied method of measurement.…”

Section: Discussionsupporting

confidence: 83%

Plasma level of mannose-binding lectin is associated with the risk of recurrent pregnancy loss but not pregnancy outcome after the diagnosis

Nørgaard-Pedersen

Rom

Steffensen

et al. 2022

Human Reproduction Open

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STUDY QUESTION Are low or high plasma mannose binding lectin (p-MBL) levels associated with recurrent pregnancy loss (RPL) and the reproductive and perinatal outcomes before and after RPL? SUMMARY ANSWER The prevalence of low p-MBL levels was significantly higher in RPL patients while high levels were significantly less prevalent. No association was found between p-MBL level and reproductive and perinatal outcomes before and after RPL. WHAT IS KNOWN ALREADY MBL is an important component in the innate immune system. Low p-MBL levels have been associated with RPL, while the correlation with high levels has been poorly studied. Adverse perinatal outcomes are generally more frequent among RPL patients, but reports concerning the association between maternal p-MBL levels and perinatal outcomes, including birth weight and gestational age, are conflicting. STUDY DESIGN, SIZE, DURATION This study was a combined cross-sectional and cohort study of 267 RPL patients admitted to the RPL Center of Western Denmark between January 2016 and March 2020. RPL patients were followed until birth of a liveborn child or until end of follow-up, March 2021. A sample of 185 healthy female blood donors of reproductive age was used as a MBL reference group. PARTICIPANTS/MATERIALS, SETTING, METHODS All RPL patients had ≥3 consecutive pregnancy losses, a regular menstrual cycle, and no known significant chromosomal or uterine malformations. At the first consultation, routine blood samples including p-MBL measurement and detailed obstetrical and perinatal information were collected. p-MBL levels in RPL patients were compared to the MBL reference group. A logistic regression analysis adjusted for relevant confounders assessed the association between low p-MBL levels and an unsuccessful reproductive outcome in RPL patients in first pregnancy after admission. Perinatal outcomes before and after RPL were compared between RPL subgroups according to low (≤500 µg/l), intermediate (501-3000 µg/l), and high (>3000 µg/l) p-MBL levels. MAIN RESULTS AND THE ROLE OF CHANCE Significantly more RPL patients had low p-MBL levels (prevalence proportion ratio [PPR]: 1.79, 95% CI: 1.34–2.38) and fewer had high p-MBL levels (PPR: 0.56, 95% CI: 0.40–0.79) compared to the reference group, while the prevalence of intermediate p-MBL level was not different between the groups (PPR: 0.86, 95% CI: 0.69-1.08). In the prospective study, low p-MBL level was not a significant risk factor for a pregnancy loss in the first pregnancy after admission after adjustment for age, BMI, and smoking. Neither before nor after the RPL diagnosis were maternal p-MBL levels significantly associated with birth weight or gestational age. LIMITATIONS, REASONS FOR CAUTION Only 161 (60.3%) patients had given birth after RPL during the follow-up period, which limited the possibility to detect clear associations between p-MBL levels and perinatal outcomes after RPL. WIDER IMPLICATIONS OF THE FINDINGS In agreement with several previous studies, low p-MBL levels are strongly associated with RPL, while this study for the first time documents that high levels may play a protective role, which suggests a causal relationship. We suggest that larger prospective studies evaluate the association between p-MBL levels and RPL prognosis. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. We acknowledge the Department of Obstetrics and Gynaecology at Aalborg University Hospital for financial support. U.S.K. has reported personal fees from Merck, consulting fees from IBSA Nordic, and a grant from Gedeon Richter, Merck and IBSA Nordic outside of the submitted work. TRIAL REGISTRATION NUMBER ID from clinicaltrials.gov is NCT04017754.

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Section: Discussionsupporting

confidence: 83%

Plasma level of mannose-binding lectin is associated with the risk of recurrent pregnancy loss but not pregnancy outcome after the diagnosis

Nørgaard-Pedersen

Rom

Steffensen

et al. 2022

Human Reproduction Open

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“…In 2001, Saevarsdottir et al [34] reported that patients with rheumatoid arthritis and low MBL levels had more serious joint damage and worse response to treatment. In 2011, Brazilian researchers found that low to moderate MBL deficiency was associated with a high incidence of lupus nephritis [35]. In recent years, Guo et al [36] confirmed that the symptoms of hematuria and infection were significantly worse in patients with low MBL levels than in those without MBL deficiency in a sample of 749 patients with IgA nephropathy; in an adjusted analysis, MBL deficiency was an independent risk factor for renal deterioration in these patients.…”

Section: Discussionmentioning

confidence: 95%

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

Zhang

Liu

Liang

et al. 2020

Kidney Blood Press Res

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Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.

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“…MBL manifests itself with immunoglobulin (Ig) G deposits in the kidney biopsy materials of patients with lupus nephropathy, membrane-proliferative glomerulonephritis, anti-glomerular basement membrane nephritis, focal segmental glomerulosclerosis, and IgA nephropathy (7) . It has been suggested that a MBL genetic defect can be related to the development of SLE; lower MBL levels serve as a risk factor in terms of SLE development (18,19) . In membranous nephropathy (MN) and Henoch-Schönlein Purpura nephritis, complement activation through the lectin pathway may play a role in the development of advanced glomerular injuries (20)(21)(22) .…”

Section: Discussionmentioning

confidence: 99%

What is the Role of Mannose-Binding Lectin Gene Polymorphism in the Development of Acute Post-Streptococcal Glomerulonephritis?

Güven¹,

Bak²,

Serdaroğlu³

et al. 2021

BUCH

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Objective: This study aims to determine the effects of the mannose-binding lectin (MBL) gene polymorphism on the clinical and laboratory findings, response to treatment, and progress of patients with acute post-streptococcal glomerulonephritis (APSGN). Methods: Codon 54 polymorphism found in exon 1 of the MBL gene was investigated by polymerase chain reaction-restriction fragment length polymorphism method in 110 children followed up with the diagnosis of APSGN and compared with healthy control group. Results: The normal allele AA and, the variant alleles AB and BB gene frequencies were determined within the APSGN group as 74.5%, 20% and, 5.5%, respectively. No statistically significant difference was found with concerning to the gene polymorphism in the APSGN group when compared with the control group (p>0.05). No correlation was found in the patient group between gene polymorphism and the presence of hematuria, edema, central nervous system findings, and blood pressure (p>0.05). Concerning laboratory findings during the diagnosis, no correlation existed between the gene polymorphism and high levels of urea, creatine, total cholesterol, and triglycerides, low levels of albumin, and the presence of proteinuria (p>0.05). Within the first years following the diagnosis, no statistically significant difference was found in the glomerular filtration rates, blood creatine levels, proteinuria levels, duration of microscopic hematuria and proteinuria between the patients with the gene polymorphism and those without the gene polymorphism (p>0.05) Conclusion: Our study determined that the MBL gene polymorphism was not important in the development, the laboratory and clinical findings, or the progression of the patients with APSGN.

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Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients

Cited by 11 publications

References 35 publications

Plasma level of mannose-binding lectin is associated with the risk of recurrent pregnancy loss but not pregnancy outcome after the diagnosis

Plasma level of mannose-binding lectin is associated with the risk of recurrent pregnancy loss but not pregnancy outcome after the diagnosis

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy

What is the Role of Mannose-Binding Lectin Gene Polymorphism in the Development of Acute Post-Streptococcal Glomerulonephritis?

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