Predictive and Prognostic Value of Ascitic Fluid Mannose Binding Lectin in Patients with Spontaneous Bacterial Peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis is a common bacterial infection of ascitic fluid, mainly in ascites due to liver cirrhosis. Mannose-binding lectin (MBL) can activate phagocytosis and the complement system. Spontaneous bacterial peritonitis was detected to be higher in MBL deficiency. This study aimed to assess ascitic fluid MBL in liver cirrhosis and spontaneous bacterial peritonitis. METHODS: Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child- Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess the severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serum-ascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid. RESULTS: Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis, fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development. CONCLUSION: Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.

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

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.

Associations of ficolins and mannose-binding lectin with acute myeloid leukaemia in adults.

We investigated clinical associations of ficolins and mannose-binding lectin (MBL) in 157 patients suffering from acute myeloid leukaemia (AML). Concentrations of ficolin-1, ficolin-2, ficolin-3 and MBL (before chemotherapy) in serum were determined as were selected polymorphisms of the corresponding genes (FCN1, FCN2, FCN3 and MBL2). The control group (C) consisted of 267 healthy unrelated individuals. Median level of ficolin-1 in patients was lower (p < 0.000001) while median levels of ficolin-2, ficolin-3 and MBL were higher (p < 0.000001, p < 0.000001 and p = 0.0016, respectively) compared with controls. These findings were generally associated with AML itself, however the highest MBL levels predicted higher risk of severe hospital infections (accompanied with bacteremia and/or fungaemia) (p = 0.012) while the lowest ficolin-1 concentrations tended to be associated with prolonged (> 7 days) fever (p = 0.026). Genotyping indicated an association of G/G homozygosity (corresponding to FCN1 gene - 542 G > A polymorphism) with malignancy [p = 0.004, OR = 2.95, 95% CI (1.41-6.16)]. Based on ROC analysis, ficolin-1, -2 and -3 may be considered candidate supplementary biomarkers of AML. Their high potential to differentiate between patients from non-malignant controls but also from persons suffering from other haematological cancers (multiple myeloma and lymphoma) was demonstrated.

Human brain trauma severity is associated with lectin complement pathway activation.

We explored the involvement of the lectin pathway of complement in post-traumatic brain injury (TBI) pathophysiology in humans. Brain samples were obtained from 28 patients who had undergone therapeutic contusion removal, within 12 h (early) or from >12 h until five days (late) from injury, and from five non-TBI patients. Imaging analysis indicated that lectin pathway initiator molecules (MBL, ficolin-1, ficolin-2 and ficolin-3), the key enzymes MASP-2 and MASP-3, and the downstream complement components (C3 fragments and TCC) were present inside and outside brain vessels in all contusions. Only ficolin-1 was found in the parenchyma of non-TBI tissues. Immunoassays in brain homogenates showed that MBL, ficolin-2 and ficolin-3 increased in TBI compared to non-TBI (2.0, 2.2 and 6.0-times) samples. MASP-2 increased with subarachnoid hemorrhage and abnormal pupil reactivity, two indicators of structural and functional damage. C3 fragments and TCC increased, respectively, by 3.5 - and 4.0-fold in TBI compared to non-TBI tissue and significantly correlated with MBL, ficolin-2, ficolin-3, MASP-2 and MASP-3 levels in the homogenates. In conclusion, we show for the first time the direct presence of lectin pathway components in human cerebral contusions and their association with injury severity, suggesting a central role for the lectin pathway in the post-traumatic pathophysiology of human TBI.

Estudio de las variables asociadas a la activación local del complemento en la nefropatía IgA idiopática / Study of the variables associated with local complement activation in IgA nephropathy

Objetivos: 1) Identificar las variables que se asocian con los niveles urinarios de MBL, C4d y C5b-9 en enfermos con nefropatía IgA idiopática. 2) Analizar si los niveles urinarios de MBL o C4d son útiles para identificar la presencia de depósitos mesangiales de C4d/MBL. Pacientes y método: Se estudió a 96 enfermos con nefropatía IgA primaria. Se registraron las variables demográficas, clínicas y bioquímicas en el momento del diagnóstico. Las lesiones renales se cuantificaron mediante la clasificación de Oxford. En las biopsias, se realizaron tinciones inmunohistoquímicas para MBL, properdina, C4d, y C5b-9. En orina, se determinó el nivel de properdina, MBL, C4d y C5b-9. Resultados: Los predictores independientes de los niveles de C4d y MBL en orina fueron el depósito mesangial de cada una de ellas y, en menor grado, la proteinuria. Los predictores independientes de los niveles urinarios de C5b-9 fueron los niveles de MBL y properdina, y la proteinuria. La excreción urinaria de C4d tuvo una sensibilidad del 90% (IC 95%: 58,7-99) y una especificidad del 73% (IC 95%: 54-87) para la detección de depósitos mesangiales de C4d y el nivel de MBL tuvo una sensibilidad del 83,9% (IC 95%: 62-95) y una especificidad del 81,6% (IC 95%: 65-92) para identificar depósitos mesangiales de MBL. Conclusión: El principal predictor de la concentración urinaria de C4d y MBL es la presencia de depósitos mesangiales de ellas. La MBL podría contribuir a la activación del complemento en la luz tubular a través de la vía de las lectinas. Los niveles urinarios de MBL y C4d podrían ser biomarcadores sensibles y específicos para la identificación de los enfermos que presentan depósitos mesangiales de MBL o C4d (AU)

Objectives: 1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. Patients and method: A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification. Immunohistochemical staining for MBL, MASP-2, properdin, C4d, and C5b-9 was performed in kidney biopsies, and in urine, the levels of properdin, MBL, C4d and C5b-9 were determined. Results: In multivariate analysis, the independent predictors of C4d and MBL levels in urine were the mesangial deposits of each protein and, to a lesser extent, the urinary protein excretion. The independent predictors of urinary levels of C5b-9 were MBL properdin and proteinuria. Urinary excretion of C4d had a sensitivity of 90% (95% CI: 58,7 to 99) and a specificity of 73% (95% CI: 54-87) for detecting mesangial C4d deposits, and the level of MBL had a sensitivity of 83.9% (95% CI: 62-95) and a specificity of 81.6% (95% CI: 65-92) for identifying mesangial deposits of MBL. Conclusion: The main predictor of urinary concentration of C4d and MBL was the presence of their respective mesangial deposits. Urine MBL may contribute to complement activation in the tubular luz through the lectin pathway. Urinary levels of MBL and C4d could be sensitive and specific biomarkers for the identification of patients with mesangial deposits of MBL and C4d (AU)

Déficit combinado de alfa-1-antitripsina y déficit de lectina fijadora de manosa / Combined alpha-1-antitrypsin deficiency and mannose-binding lectin deficiency

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The prognostic performance of the complement system in septic patients in emergency department: a cohort study.

AIM: To investigate the prognostic performance of complement components in septic patients, complement 3, membrane attack complex (MAC) and mannose-binding lectin were measured and compared among adult patients with sepsis, severe sepsis and septic shock, as well as between in-hospital nonsurvivors and survivors. METHODS: The prognostic value of complement components was compared with mortality in emergency department sepsis (MEDS) score. RESULTS: Median complement 3, MAC and mannose-binding lectin increased directly with the sepsis, severe sepsis and septic shock groups, and were significantly higher in nonsurvivors than in survivors. CONCLUSION: MEDS and MAC independently predicted in-hospital mortality. The prognostic performance of MAC was superior to MEDS as analyzed by receiver operating characteristic curve and area under the curve.

Agarose gel shift assay reveals that calreticulin favors substrates with a quaternary structure in solution.

Here we present an agarose gel shift assay that, in contrast to other electrophoresis approaches, is loaded in the center of the gel. This allows proteins to migrate in either direction according to their isoelectric points. Therefore, the presented assay enables a direct visualization, separation, and prefractionation of protein interactions in solution independent of isoelectric point. We demonstrate that this assay is compatible with immunochemical methods and mass spectrometry. The assay was used to investigate interactions with several potential substrates for calreticulin, a chaperone that is involved in different biological aspects through interaction with other proteins. The current analytical assays used to investigate these interactions are mainly spectroscopic aggregation assays or solid phase assays that do not provide a direct visualization of the stable protein complex but rather provide an indirect measure of interactions. Therefore, no interaction studies between calreticulin and substrates in solution have been investigated previously. The results presented here indicate that calreticulin has a preference for substrates with a quaternary structure and primarily ß-sheets in their secondary structure. It is also demonstrated that the agarose gel shift assay is useful in the study of other protein interactions and can be used as an alternative method to native polyacrylamide gel electrophoresis.

Complement Factor C4d Is a Common Denominator in Thrombotic Microangiopathy.

Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can occur in a variety of clinical conditions. Promising results of recent trials with terminal complement-inhibiting drugs call for biomarkers identifying patients who might benefit from this treatment. The primary aim of this study was to determine the prevalence and localization of complement factor C4d in kidneys of patients with TMA. The secondary aims were to determine which complement pathways lead to C4d deposition and to determine whether complement activation results in deposition of the terminal complement complex. We examined 42 renal sections with histologically confirmed TMA obtained from a heterogeneous patient group. Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d deposits were present in 88.1% of TMA cases, and the various clinical conditions had distinct staining patterns within the various compartments of the renal vasculature. Classical pathway activation was observed in 90.5% of TMA cases. C5b-9 deposits were present in 78.6% of TMA cases and in 39.6% of controls (n=53), but the staining pattern differed between cases and controls. In conclusion, C4d is a common finding in TMA, regardless of the underlying clinical condition. Moreover, C5b-9 was present in >75% of the TMA samples, suggesting that terminal complement inhibitors may have a beneficial effect in these patients. C4d and C5b-9 should be investigated as possible diagnostic biomarkers in the clinical work-up of patients suspected of having complement-mediated TMA.

The immunological investigation of a child with chronic wet cough.

Immunological investigations need to be considered in any child presenting with chronic wet cough. Not infrequently, such children are subjected to a detailed, expensive battery of immune function tests, without consideration as to whether such extensive testing is necessary or indeed helpful. The main aim of this review is to discuss which immune function tests are and are not particularly helpful when investigating a child with persistent wet cough.

Pulmonary innate immunity in children with protracted bacterial bronchitis.

OBJECTIVE: To determine bronchoalveolar lavage (BAL) levels of 3 innate immunity components (human ß-defensin-2 [hBD2], mannose-binding lectin [MBL], and surfactant protein-A [SP-A]), the relationship with airway neutrophilia and infection, and cytokine production of stimulated BAL cells in children with current protracted bacterial bronchitis (PBB), children with resolved PBB (PBB well), and controls. STUDY DESIGN: BAL of 102 children (mean age 2.8 years) fulfilling predefined criteria of current PBB (n = 61), PBB well (n = 20), and controls (n = 21) was cultured (quantitative bacteriology) and viruses examined by polymerase chain reaction. hBD2, MBL, and SP-A were measured, and cytokine production by lipopolysaccharide-stimulated BAL cells was determined. RESULTS: Median hBD2 and MBL levels were significantly higher in the current PBB group (hBD2 = 164.4, IQR 0-435.5 pg/mL; MBL = 1.7, 0.4-4 ng/mL) than in the PBB well group (hBD2 = 0, IQR 0-85.2; MBL = 0.6, IQR 0.03-2.9) and controls (hBD2 = 3.6, IQR 0-126; MBL = 0.4, IQR 0.02-79). hBD2 was significantly higher in children with airway infection (n = 54; median 76.9, IQR 0-397.3) compared with those without (n = 48; 0, IQR 0-236.3), P= .04. SP-A levels and cytokine production of stimulated BAL cells were similar between groups. CONCLUSION: In children's airways, hBD2, but not MBL and SP-A, relates to inflammation and infection. In children with PBB, mechanisms involving airway hBD2 and MBL are augmented. These pulmonary innate immunity components and the ability of BAL cells to respond to stimuli are unlikely to be deficient.

Mannose-binding lectin serum levels in neonatal sepsis and septic shock.

OBJECTIVE: To evaluate mannose-binding lectin (MBL) serum levels as a marker for predicting sepsis, septic shock, and their outcomes in neonates. PATIENTS AND METHODS: A prospective study was conducted on 62 neonates (27 preterm and 35 full term) with culture-proven sepsis and 35 controls. Serum levels of MBL were measured by immunoassay. RESULTS: Of 62 infants with positive blood cultures (Gram-negative = 44 and Gram-positive = 18), 11 infants had severe sepsis and 6 neonates developed septic shock. MBL levels were significantly lower in infants with sepsis than in control group (0.39 ±â€Š0.07 vs. 1.34 ±â€Š0.03 µg/ml; p < 0.001). The lowest MBL levels were detected in those infants with septic shock, particularly those who died (p < 0.05). MBL had high sensitivity (96.7), specificity (97.1), positive (98.3), and negative (94.4) predictive values to detect sepsis. CONCLUSION: Low MBL serum levels could be considered as sensitive and specific marker for predicting sepsis, septic shock, and their clinical outcomes in newborn infants.

Determinação dos níveis séricos de lectina ligada a manose e citocinas em pacientes de lacaziose e a associação destes com as formas clínicas da doença / Determination of serum levels of mannose binding lectin and cytokines in lacaziosis patients and the association of them with the clinical forms of disease

A lacaziose é uma micose cutânea – subcutânea de evolução crônica, cujo agente etiológico é a Lacazia loboi (L. loboi). A suscetibilidade a infecção e desenvolvimento da doença pode se manifestar diferentemente de um indivíduo para outro. Isto pode ser atribuído a inúmeros fatores como a deficiência de lectina ligada a manose – MBL (mannose binding lectin) e distúrbios no equilíbrio da produção e liberação das citocinas. No entanto, entre MBL e doenças fúngicas poucos estudos são encontrados na literatura, assim como para algumas determinações séricas de citocinas. Diante disso, a análise da associação entre as manifestações clínicas e níveis séricos destes mediadores é de fundamental importância para avaliar o padrão de resposta imune inata e adaptativa nos portadores de lacaziose da região de Rio branco (AC). Assim, o objetivo deste estudo foi avaliar os níveis séricos de MBL e das citocinas (IL-4, IL-6, IL-10, IL-17, IL-22, TGF-Beta1 e IFN-Gama) em pacientes com a doença nas suas distintas formas clínicas...

Lacaziosis is a cutaneous – subcutaneous mycosis of chronic evolution, whose etiologic agent is Lacazia loboi (L. loboi). The infection susceptibility and disease development can manifest differently in one individual to another. It can be due to many factors, like the deficiency of mannose binding lectin - MBL and disturb the balance of the production and release of cytokines. However, few studies are found in the literature of MBL and fungal diseases and likewise some on serum cytokines determinations. The analysis of the association between clinical manifestations and serum levels of these mediators is of fundamental importance in evaluating the standard of innate and adaptive immune response of the Jorge Lobo’s disease patients the of Rio Branco (AC) region. Through carrying out this type of analysis, the objective of this study was to evaluate serum levels of MBL and cytokines (IL-4, IL-6, IL-10, IL-17, IL-22, TGF-Beta1 and IFN-Gamma) in patients with disease in their distinct clinical form...

Low-mannose-binding lectin levels in susceptibility to neonatal sepsis in preterm neonates with fetal inflammatory response syndrome.

AIM: In this study, we aimed to evaluate cord blood mannose binding levels (MBL), to evaluate possible relationship between cord blood MBL levels with neonatal sepsis and culture confirmed neonatal sepsis in preterm newborn with gestational age below 34 weeks with fetal inflammatory response syndrome (FIRS). METHODS: Forty-four randomly selected < or =34 weeks gestational age newborns with FIRS were evaluated. MBL deficiency was described as cord blood levels were below 400 ng/ml. RESULTS: Mean value of umbilical cord MBL was significantly lower in newborns with culture confirmed sepsis (p < 0.01) and also all cases with sepsis (including culture negative or positive) (p < 0.05) than newborns without sepsis. Culture-confirmed sepsis was statistically common in MBL deficient premature newborns with FIRS. Univariate analysis showed that gestational age, birth weight, low serum MBL level and poor obstetric history were all significantly associated with the risk of neonatal sepsis. A subsequent multivariate analysis showed that the association between serum MBL level and the risk of suspected sepsis and culture confirmed sepsis independently from gestational age and birth weight. CONCLUSION: Here in, we report firstly lower MBL levels were found related with sepsis in neonates, especially in newborns with culture proven sepsis. Low MBL levels may help to identify neonates with FIRS at high risk of developing sepsis.

Mannose binding lectin levels are not related to radiographic damage in ankylosing spondylitis.

In the current study we aimed to investigate the effect of MBL deficiency in radiographic damage of the spine in a large group of AS patients. One hundred and ninety-one AS patients and 85 healthy controls were studied. Disease activity, radiological scores, and demographic features were recorded. MBL levels were measured with standard ELISA kits. Results showed that median MBL levels in AS and healthy controls were 2,530 (range 0-5,861) ng/ml and 3,415 (0-7,950) ng/ml, respectively (p = 0.1). MBL deficiency (<500 ng/ml) was comparable in both groups (%21.5 in AS, % 17.6; p = 0.5). Disease activity, clinical picture, and therapies were not associated with MBL levels. Both BASRI and mSASSS scores were found similar in AS patients with or without MBL deficiency [BASRI: MBL < 500 ng/ml: 6(2-12), MBL >or= 500 ng/ml: 6(2-12); p = 0.75], [mSASSS: MBL < 500 ng/ml: 3(0-72), MBL >or= 500 ng/ml: 5(0-72); p = 0.81]. We conclude that MBL deficiency prevalence is not increased in AS patients and it is not a cause of a severe radiographic damage.

Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro.

Mannose-binding lectin (MBL) is an innate immune molecule present in blood and some mucosal tissues, which can influence microbial attachment and inflammatory responses of host cells during infection. In this study MBL was found to be present at a low concentration in semen samples in the range 1.2-24.9 ng/ml. Co-incubation of bacteria with semen resulted in the binding of MBL to the bacterial surface. Neisseria gonorrhoeae is a common cause of genitourinary infection. MBL bound to N. gonorrhoeae with strain-to-strain variation in the intensity of binding and nature of the bacterial receptor. Pretreatment with MBL concentrations similar to those found in human serum modulated the adhesion of N. gonorrhoeae strain FA1090 but not strain MS11 to epithelial cells. This effect was dose-dependent. This work demonstrates that MBL is present in human semen and modifies cellular responses to N. gonorrhoeae in a concentration-dependent manner.

Detection and identification of plasma proteins that bind GlialCAM using ProteinChip arrays, SELDI-TOF MS, and nano-LC MS/MS.

In order to fully understand biological processes it is essential to identify interactions in protein complexes. There are several techniques available to study this type of interactions, such as yeast two-hybrid screens, affinity chromatography, and coimmunoprecipitation. We propose a novel strategy to identify protein-protein interactions, comprised of first detecting the interactions using ProteinChips and SELDI-TOF MS, followed by the isolation of the interacting proteins through affinity beads and RP-HPLC and finally identifying the proteins using nano-LC MS/MS. The advantages of this new strategy are that the primary high-throughput screening of samples can be performed with small amounts of sample, no specific antibody is needed and the proteins represented on the SELDI-TOF MS spectra can be identified with high confidence. Furthermore, the method is faster and less labor-intensive than other current approaches. Using this novel method, we isolated and identified the interactions of two mouse plasma proteins, mannose binding lectin C and properdin, with GlialCAM, a type 1 transmembrane glycoprotein that belongs to the Ig superfamily.

AIDS patients have increased surfactant protein D but normal mannose binding lectin levels in lung fluid.

BACKGROUND: Surfactant protein D (SP-D) and Mannose Binding Lectin (MBL) are collectins that have opsonic and immunoregulatory functions, are found in lung fluid and interact with the human immunodeficiency virus (HIV). We compared collectin levels in lung fluid and serum from HIV infected and normal subjects to determine if alterations in lung collectin levels were associated with HIV infection and might result in increased susceptibility to other pulmonary infections. METHODS: Blood and bronchoalveolar lavage samples were collected from 19 HIV-infected individuals and 17 HIV-uninfected individuals, all with normal chest X ray at time of study. HIV viral loads and peripheral blood CD4+ T cell counts were measured in all subjects. SP-D was measured in lung fluid, and MBL in both lung fluid and serum. RESULTS: SP-D levels were not significantly different in lung fluid from HIV-uninfected (median 406.72 ng/ml) and HIV-infected individuals with high CD4 count (CD4 >200) (median 382.60 ng/ml) but were elevated in HIV-infected individuals with low CD4 count (median 577.79 ng/ml; Kruskall Wallis p < 0.05). MBL levels in serum were not significantly different between HIV-uninfected and HIV-infected individuals (median 1782.70 ng/ml vs 2639.73 ng/ml) and were not detectable in lung fluid. CONCLUSION: SP-D levels are increased in lung fluid from AIDS patients but not in patients with early HIV infection. MBL levels are not altered by HIV infection or AIDS. There is no evidence that altered pulmonary collectin levels result in susceptibility to infection in these patients.

Mannan-binding lectin (MBL) in women with tumours of the reproductive system.

Mannan-binding lectin (MBL) is an important factor of innate immunity contributing to the clearance of microorganisms. Recently, an antitumourigenic role of MBL has been suggested. We investigated mbl2 genotypes, MBL concentrations, and MBL-MASP-2 complex activity in patients with ovarian cancer. The expression of both mbl2 and masp-2 genes were investigated in ovarian tissue sections. Additionally, samples from patients with other malignant and benign tumours of the reproductive tract were tested. A significantly higher incidence of MBL deficiency/insufficiency-associated genotypes was found among patients with malignant disease compared to age-matched controls. Unexpectedly, no differences in median MBL level or MBL-MASP-2 complex activity were found between the groups. This was partly a reflection of higher MBL concentrations and MBL-MASP-2 activity in cancer patients compared with healthy women carrying corresponding genotypes. MBL-specific mRNA expression was detected in several normal and malignant ovarian tissues, as well as in ovarian epithelial cell lines. Intracellular staining with MBL-specific antibodies demonstrated the presence of MBL in ovarian cell lines, and in normal as well as malignant ovarian tissue sections. In contrast, MASP-2-specific mRNA expression was detected only in the ovary tissues of patients with malignant disease. No significant changes in MBL concentration during 3 months of chemotherapy were noticed. MBL was detected in ascites and in the fluid of benign ovarian cysts. Our findings may reflect anti-tumourigenic activity of MBL protein which might suggest potential therapeutic application. However, it cannot be excluded that mbl-2 mutant alleles may be in linkage disequilibrium with an unidentified tumour susceptibility gene(s).