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The State of Parana has a diversity of plants that are used in the traditional medicine and among them are some of the representatives of the Piperaceae family. Piper is the one of the most important genera of this family and its species show similar morphology and different biological activities. The literature shows that approximately 54 species of Piper have been described in the State of Parana. The purpose of this study is to gather key information by means of electronic databases, about the morphoanatomy and biological activities of species of Piper found in the State of Parana. The results with regard to the morphoanatomy show that, on the whole, the species that have been described possess hypostomatic leaves, non-glandular and glandular trichomes, and calcium oxalate crystals in the leaves and stems. Several biological activities have been reported, including antimicrobial, anti-inflammatory, antifungal, digestive, diuretic, insecticidal, leishmanicidal, pesticide and trypanocide.

Intending to highlight new fruits with nutraceutical potential, the present work reports the nutritional and antioxidant content of Syzygium cumini (L.) Skeels (S. cumini) and Syzygium malaccense (L.) Merr. & LM Perry (S. malaccense), and evaluates the anticancer potential against CP-H460 (lung carcinoma line) and its functionality over HEK-293 (healthy embryonic kidney line), two human cells. For this, the physical-chemical characterization of the lyophilized fruits was carried out, and the content of total phenolic compounds (Folin-Ciocalteau) and the antioxidant potential (DPPH, FRAP, and ORAC) was determined. For anticancer activity, aqueous extracts were prepared and evaluated using the MTT (3-[4,5-dimethyl-triazol-2-yl]-2,5-diphenyltetrazolium) assay for periods of 20 hours. These two species are rich in dietary fibers, mainly insoluble fibers, and are sources of natural compounds and antioxidants, which possibly explain the protective potential against cancer cells. Thus, it is expected, as two source fruits, results obtained (p

Aims To investigate whether FCN3 polymorphisms and circulating ficolin-3 levels were associated with clinical forms of chronic Chagas disease (CD) and to assess their potential use as biomarkers for the disease or its severity. Methods and results FCN3 polymorphisms (g.1637delC (rs532781899) in exon 5; g.3524_3532insTATTTGGCC (rs28362807) in intron 5 and g.4473C > A) (rs4494157) in intron 7) were determined in 178 chronic CD patients (65 asymptomatic, 68 cardiac, 21 digestive and 24 cardiodigestive), and 285 healthy controls by sequence-specific PCR. Ficolin-3 serum levels, measured by ELISA in 80 patients and 80 controls, did not differ between groups. On the other hand, ficolin-3 levels were positively correlated with left ventricular ejection fraction (P = .002; r = .5), with lower levels associated with increased risk of cardiac insufficiency (P = .033; OR 7.21, 95%IC 1.17-44.4). Ficolin-3 levels were positively correlated with ficolin-2 (P = .021; r = .63), and negatively with MBL (P = .002; r = -.36) and pentraxin-3 (P = .04; r = -.32) levels. No significant results were observed for the investigated FCN3 polymorphisms and CD. The g.1637del/1637C heterozygotes presented lower ficolin-3 levels than g.1637C/1637C homozygotes in the control group (P = .023). Conclusion Low ficolin-3 levels may play a role in the pathophysiology of cardiac insufficiency associated with CD.

Visceral Leishmaniasis is an infectious disease that affects mainly humans and dogs, with the latter being important reservoirs of the parasite. Conversely, cats are naturally resistant. The immune system can offer important explanation to this problematic as there is no evidence on the role that the complement system plays in cats. In this context, effect of the complement system from human, dog and cat sera on Leishmania infantum was evaluated. Activation of the classical, alternative and lectin pathways was assessed through hemolytic and ELISA assays. Lytic activity of the complement on the parasite's viability was investigated by Transmission Electron Microscopy and Flow Cytometry. Complement proteins were more consumed in dog serum on the classical and alternative pathways, leading to less hemolytic activity, and only in cat serum they were consumed on the lectin pathway when incubated with L. infantum. Lytic activity on the parasite's surface was more accentuated in human serum, and varied throughout the parasite's developmental stages.

Leishmania (Viannia) braziliensis is the main agent of mucocutaneous Leishmaniasis, a neglected tropical disease that affects thousands of people in Brazil. It has been shown that complement plays a critical role at early stages of Leishmania infection and that is involved in the invasion of macrophages by the promastigotes. Ficolins and collectins are soluble pattern recognition and triggering molecules of the lectin complement pathway. We investigated here whether lectin pathway activators ficolin-1, ficolin-2, ficolin-3 and CL-11 bind to live L. braziliensis promastigotes in vitro. Promastigote forms in the stationary growth phase were incubated with normal human serum (NHS) or recombinant ficolins 1, 2 and 3, MBL and CL-11, and protein binding was evaluated by confocal microscopy and flow cytometry. Ficolins 1, 2 and 3, MBL and CL-11 were able to bind to the surface of live promastigotes after incubation with either NHS or recombinant proteins. A partial inhibition by N-acetyl-d-glucosamine characterizing the participation of acetylated groups in the deposition of ficolins and CL-11 to glycoconjugates on the surface of L. braziliensis was observed. These evidences highlight a role for the lectin pathway in the innate response to L. braziliensis.

Chagas disease (CD), caused by infection with the parasite Trypanosoma cruzi, leads to severe cardiomyopathy in 20-30% of patients, whereas the remainder may stay asymptomatic and never develop cardiomyopathy or other clinical manifestations. The underlying cause for this variable outcome is not fully characterized, although previous studies have found high levels of circulating mannose-binding lectin (MBL) to be associated with cardiac failure echocardiographic changes. We report three indeterminate (asymptomatic) chronic Chagas patients who were followed up for 10 years. Two of these patients developed chronic chagasic cardiomyopathy (CCC) during this follow-up period and, when genotyped, were found to be carriers of the high MBL producer HYPA/HYPA genotype, suggesting that genetically determined high MBL serum might be associated with the risk of CCC development. These results suggest the use of MBL quantification and MBL2 genotyping as tools for clinical assessment in patients with chronic CD.

Background Medicinal plants are an important source to identify new active pharmaceutical compounds. Traditionally, the sap of Euphorbia umbellata is widely used to treat cancer and inflammatory conditions. These effects have been attributed to the presence of terpenes and phenolic compounds in the extracts of this plant. Euphol, a tetracyclic triterpene alcohol, is one of the major compounds present in Euphorbia species, and some biological activities have been attributed to this compound. Purpose This study aimed to evaluate the in vitro cytotoxicity of euphol against Jurkat, HL-60, K-562, B16F10, and HRT-18 cells lines, as well as the biological stability, distribution, metabolism properties in vitro, and the determination of the concentration of euphol in the plasma and liver of rats. Methods The MTT reduction assay was used to evaluate the cytotoxicity of euphol against cancer cell lines, and the selectivity index, the morphology and cell cycle assays to evaluate the death mechanisms in K-562 and B16F10 lineages. UHPLC-MS was applied for the in vivo evaluation of the concentration of euphol in plasma and liver, and in vitro metabolic stability in human liver microsomes and S9 fraction, plasma protein binding, and stability in simulated gastric and intestinal fluids assays. Conclusions This study demonstrated that euphol exhibited cytotoxic effects against a variety of cancer cells lines, selectivity against leukemia and possibly, the mechanism involved is apoptosis. The evaluation of stability, distribution, and metabolism properties showed that euphol was unstable in gastric and intestinal fluids, presenting moderate plasma protein binding with two hours elimination half-life and possible phase II liver metabolism. All the results suggested that further studies could be developed to prove the viability of euphol as an anticancer agent.

Several studies have examined the complement system in schizophrenia, suggesting an involvement of the lectin pathway. We analyzed 49 patients with schizophrenia and explored the association between psychopathology of schizophrenia and complement component 3 (C3) serum levels, C-reactive protein (CRP) serum levels, ficolin activation, and mannose-binding lectin (MBL) activation. In the multiple regression analysis, a negative association was observed between the Positive and Negative Syndrome Scale (PANSS) total score and ficolin activation. Body mass index (BMI) was positively associated with the serum levels of C3 and CRP. MBL activation was not associated with any independent variables. Our findings facilitate a better understanding of the complement system in schizophrenia. Additional studies with a large sample population are needed to confirm our results.

Visceral leishmaniasis (VL) is a neglected and highly lethal disease. VL is endemic in South American countries, with Brazil being responsible for 96% of the cases. In this continent, VL is caused by the protozoan Leishmania (Leishmania) infantum (L. infantum), transmitted by the bite of infected female phlebotomine sandflies. Immediately after the inoculation of L. infantum promastigotes into the vertebrate host, the complement, as part of the first line of innate response, becomes activated. L. infantum promastigotes glycocalyx is rich in carbohydrates that can activate the lectin pathway of complement system. In this study, we evaluated whether the lectin pathway collectins [manose binding lectin (MBL) and collectin-11 (CL-11)] and ficolins (-1, -2 and -3) interact with L. infantum promastigotes, using confocal microscopy and flow cytometry. The binding of MBL, CL-11 and ficolins -1 and -3, but not ficolin-2, was observed on the surface of live metacyclic promastigotes after incubation with normal human serum (NHS) or recombinant proteins. C3 and C4 deposition as well as complement mediated lyses was also demonstrated after interaction with NHS. These results highlight a role for collectins and ficolins in the initial immune response to L. infantum.

This paper reports the assessment of bioactivity of inflorescences extracts of Musa paradisiaca L. obtained using supercritical CO2 (scCO2) and compressed propane as solvents. The effects of extraction conditions over the antioxidant and antibacterial activity were evaluated. The highest antioxidant activity (3576.86 ± 18.36 mg of ɑ-tocopherol/g extract) was found for extracts obtained using scCO2 as solvent at 353.15 K and 25.0 MPa. The extracts did not showed inhibition for the bacteria tested. The immunomodulatory effects of the extracts obtained by the extraction with 308.15 K and 3.0 MPa showed a significant inhibitory effect on the alternative pathway (AP) in all concentrations tested (333–5.2 μg mL−1), with at least 70% reduction in the AP-induced haemolysis when compared with the 100% haemolysis control without the use of the extract.

Infections are usually involved in the pathogenesis of spondyloarthritis (SpA). Mannose-binding lectin (MBL) is a component of the innate immune system with an important role in microbial defense.To study the prevalence of MBL deficiency in SpA patients as well as its influence in the clinical profile of these diseases.We studied 89 SpA patients and 89 healthy individuals, paired for age and gender. MBL serum levels were measured by ELISA test. Individuals with levels ≤100 ng/mL were considered deficient. SpA patients had determination of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, Bath Ankylosing Spondylitis Functional Index (BASFI), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and review of their clinical profile.SpA patients had MBL levels ranging from 100 to 4100 ng/mL (median = 375 ng/mL); controls levels ranged from 100 to 4703 ng/mL (median = 1204 ng/mL; p0.0001). The prevalence of MBL deficiency was 27/89 (30.3%) in SpA patients and 12/89 (13.5%) in controls, with p = 0.01; OR = 2.5 (95% IC = 1.2-5.3). No association/correlation was found between MBL levels with BASDAI, BASFI, age at disease onset, ASDAS-CRP, ESR, CRP, presence of uveitis, HLAB27, peripheral arthritis, or SpA subtype (all p = NS).MBL levels may be linked with the occurrence of SpA but do not influence its phenotype.

Background Leprosy patients may present several osteoarticular complaints, which require further evaluation of inflammatory diseases, such as rheumatoid arthritis (RA). Therefore, an adequate clinical assessment in addition to testing for rheumatoid factors (RF) and anticyclic citrullinated peptide antibodies (anti-CCP), can be useful in order to establish the correct diagnosis. Method In this study, the relation of RF and anti-CCP with rheumatological manifestations was evaluated in 97 leprosy patients from Southern Brazil. The results were compared to RA patients and healthy controls from the same geographical area and ethnic background. Results Neuropathy was observed in 71.1% and arthritis in 35.1% of the leprosy patients. A high frequency of RF positivity was observed among the leprosy patients (41.2%, 40/97), with RF immunoglobulin A (IgA) significantly associated with arthritis (OR = 7.9, 95% CI = 1.5–40.6 P = 0.008). Anti-CCP was observed in 9.3% (9/97) of the patients, with anti-CCP2 being the most frequent subtype. Only 4.1% (4/97) of the patients were RF and anti-CCP concomitantly positive. RF IgM showed a significant association with leprosy when compared to healthy controls (P

Piper amalago L., Piperaceae, popularly known as jaborandi-manso, is a shrub that spans a height of 2–7 m. It can be found in the regions of Southern America downward up to the south of Brazil. Traditionally it is used to treat digestive problems, heart problems, and burns. This study aims to conduct an anatomical investigation and analysis of the leaves and stems of P. amalago through electron scanning and optical micro techniques. The analysis showed that P. amalago has a hypostomatic leaf, with a subepidermal layer on its surface. There are grandular trichomes that resemble sacs, conic non-glandular trichomes, dorsiventral mesophyll, and a plano-convex midrib having a single vascular bundle in the center. The petiole is short with irregularly shaped and adaxially grooved. The stem is circular in shape and contains two circles of vascular bundles and a sclerenchymatic sheath in the perimedular region. These anatomical features of the Piper amalago's leaves and stems make it easy to pick it out among other species of the Piper genus. This is helpful when conducting quality control process. Keywords: Anatomy, Quality control, Jaborandi-manso, Piper amalago, Piperaceae

We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas' disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycaemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol) and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography examinations. Comparisons between chronic CD clinical forms were performed using Mann-Whitney test and correlation Spearman's test. FH levels were correlated positively with triglycerides (P = .001, r = .39), LDL-C (P = .009, r = .3), cholesterol (P = .02, r = .28), uCRP (P = .029, r = .31) and BMI (P = .008, r = .34); and negatively with HDL-C (P = .03, r = -.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels was observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD.

Background/Aims: Arthropathy is the most common extraintestinal manifestation observed in patients with Crohn's disease (CD). The present study aimed to screen rheumatoid arthritis (RA) using anti-CCP antibodies and rheumatoid factor (RF) in CD patients from Southern Brazil. Additionally, the presence of arthralgia and spondyloarthritis (SpA) was evaluated. CD patients, previously diagnosed using clinical data, imaging tests, endoscopic and histological findings, were included consecutively. Methods: A total of 100 patients participated in the study, of which 60% were female, with a mean age of 41.9 ± 12.04 (16-83 years). As controls, sera from 100 healthy individuals from the same geographic area were analyzed. Results: Arthralgias were present in 55% of the patients, being more frequent in women (65.5%; 36/55), than in males (34.5%). No association was found between arthralgia and the treatment method used. Six patients (6/100) had SpA previously diagnosed. In the CD group, anti-CCP was positive only in one patient, while RF was positive in 7 patients (7%; 7/100). The anti-CCP positive patient (woman, 38 years old, RF positive), fulfilled the ACR criteria and was diagnosed as RA. In the control group, anti-CCP antibodies were detected in 1% (1/100) and RF was positive in 6 of the samples (6%). Conclusion: Our data showed low frequency of anti-CCP antibodies and RF in Brazilian patients with CD. Additionally, we found a high prevalence of arthralgia in these patients, with 6% of them diagnosed with SpA.

To investigate the association between mannose-binding lectin (MBL) serum level and MBL2 polymorphisms, and the frequency of spontaneous miscarriages in rheumatoid arthritis (RA) patients.One hundred seventy seven women (mean age 50 years) with RA from Southern Brazil were studied and 4.5% had a history of abortion (8/177). The MBL levels were determined by ELISA. MBL2 polymorphisms in the promoter (-550H/L, -221X/Y), 5' untranslated region (4 P/Q) and exon 1 (p.Gly54Asp: B allele, p.Arg52Cys: D allele and p.Gly57Glu: C allele; collectively labelled O) were genotyped by sequencing.Mannose-binding lectin levels of RA patients ranged from ≤100 ng/mL to 6640 ng/mL (median 541.5 ng/mL). There was a significant difference in MBL median levels (100 ng/mL vs. 625 ng/mL, respectively, p = .001) and frequency of MBL deficiency (75.0% vs. 24.1%, p = .007, OR = 10.3, 95%CI = 1.9-55.4), in patients with a history of miscarriage vs those without it. Patients with RA and miscarriage had more frequently haplotypes related with low MBL levels (p = .007, OR = 10.5, 95%CI = 1.3-84) than high producers. Moreover, LYPB haplotype and O allele were significantly associated with the occurrence of miscarriage (p = .001, OR = 9.7, 95%CI = 2.4-39.1 and p = .009, OR = 5.9, 95%CI = 1.4-23.4, respectively).The results suggest that MBL deficiency and the presence of MBL2 gene polymorphisms that lead to MBL deficiency are risk factors for the occurrence of miscarriage in patients with RA.

Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are components of the lectin pathway, which activate the complement system after binding to the HCV structural proteins E1 and E2. We haplotyped 11 MASP2 polymorphisms in 103 HCV patients and 205 controls and measured MASP-2 levels in 67 HCV patients and 77 controls to better understand the role of MASP-2 in hepatitis C susceptibility and disease severity according to viral genotype and fibrosis levels. The haplotype block MASP2*ARDP was associated with protection against HCV infection (OR = 0.49, p = .044) and lower MASP-2 levels in controls (p = .021), while haplotype block AGTDVRC was significantly increased in patients (OR = 7.58, p = .003). MASP-2 levels were lower in patients than in controls (p

Trypanosoma cruzi is a protozoan parasite known to cause Chagas disease (CD), a neglected sickness that affects around 6–8 million people worldwide. Originally, CD was mainly found in Latin America but more recently, it has been spread to countries in North America, Asia, and Europe due the international migration from endemic areas. Thus, at present CD represents an important concern of global public health. Most of individuals that are infected by T. cruzi may remain in asymptomatic form all lifelong, but up to 40% of them will develop cardiomyopathy, digestive mega syndromes, or both. The interaction between the T. cruzi infective forms and host-related immune factors represents a key point for a better understanding of the physiopathology of CD. In this context, the complement, as one of the first line of host defense against infection was shown to play an important role in recognizing T. cruzi metacyclic trypomastigotes and in controlling parasite invasion. The complement consists of at least 35 or more plasma proteins and cell surface receptors/regulators, which can be activated by three pathways: classical (CP), lectin (LP), and alternative (AP). The CP and LP are mainly initiated by immune complexes or pathogen-associated molecular patterns (PAMPs), respectively, whereas AP is spontaneously activated by hydrolysis of C3. Once activated, several relevant complement functions are generated which include opsonization and phagocytosis of particles or microorganisms and cell lysis. An important step during T. cruzi infection is when intracellular trypomastigotes are release to bloodstream where they may be target by complement. Nevertheless, the parasite uses a sequence of events in order to escape from complement-mediated lysis. In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 convertase, a key step in the activation of complement. Moreover, T. cruzi promotes secretion of plasma membrane-derived vesicles from host cells, which prevent the activity of C3 convertase C4b2a and thereby may hinder complement. In this review, we aim to present an overview on the strategies used by T. cruzi in order to circumvent the activation of complement and, consequently, its biological effects.

Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/FCN3 gene impact on leprosy is currently unknown. The aim of the present study was to investigate if FCN3 polymorphisms (rs532781899: g.1637delC, rs28362807: g.3524_3532insTATTTGGCC and rs4494157: g.4473C>A) and ficolin-3 serum levels play a role in the susceptibility to leprosy. We genotyped up to 190 leprosy patients (being 114 (60%) lepromatous), and up to 245 controls with sequence-specific PCR. We also measured protein levels using ELISA in 61 leprosy and 73 controls. FCN3 polymorphisms were not associated with disease, but ficolin-3 levels were higher in patients with FCN3 *2B1 (CinsA) haplotype (p = 0.032). Median concentration of ficolin-3 was higher in leprosy per se (26034 ng/mL, p = 0.005) and lepromatous patients (28295 ng/mL, p = 0.016) than controls (18231 ng/mL). In addition, high ficolin-3 levels (>33362 ng/mL) were more common in leprosy per se (34.4%) and in lepromatous patients (35.5%) than controls (19.2%; p = 0.045 and p = 0.047, respectively). Our results lead us to suggest that polymorphisms in the FCN3 gene cooperate to increase ficolin-3 concentration and that it might contribute to leprosy susceptibility by favoring M. leprae infection., Author summary Leprosy is considered a neglected disease and still a public health problem in many countries where it was not yet eliminated, leading to a high disability rate and social stigma. The molecular mechanisms of M. leprae infection and immune evasion are still poorly known, raising the need for studies that may contribute to a better understanding of leprosy etiology, as well as improvement in diagnosis and treatment. Ficolin-3 is a soluble molecule of the innate immune system that recognizes a wide range of pathogen-associated molecular patterns leading to complement activation and phagocytosis. We observed high concentration of ficolin-3 in leprosy patients, likely caused by polymorphisms present in intronic regions of FCN3 gene, which may contribute to leprosy susceptibility by favoring M. leprae infection. This is the first study addressing FCN3 polymorphisms and ficolin-3 levels in leprosy, indicating it as a good candidate biomarker associated with the host response against M. leprae.

The aim of the present study was to detect natural infection by Leishmania (Leishmania) infantum in Lutzomyia longipalpis captured in Barcarena, state of Pará, Brazil, through the use of three primer sets. With this approach, it is unnecessary to previously dissect the sandfly specimens. DNA of 280 Lu. longipalpis female specimens were extracted from the whole insects. PCR primers for kinetoplast minicircle DNA (kDNA), the mini-exon gene and the small subunit ribosomal RNA (SSU-rRNA) gene of Leishmania were used, generating fragments of 400 bp, 780 bp and 603 bp, respectively. Infection by the parasite was found with the kDNA primer in 8.6% of the cases, with the mini-exon gene primer in 7.1% of the cases and with the SSU-rRNA gene primer in 5.3% of the cases. These data show the importance of polymerase chain reaction as a tool for investigating the molecular epidemiology of visceral leishmaniasis by estimating the risk of disease transmission in endemic areas, with the kDNA primer representing the most reliable marker for the parasite.

Objective: The aim of this study was to investigate the frequency of the LCT*-13910C>T polymorphism associated with a high expression of lactase in the small intestine during adulthood, and to infer the lactase persistence and adult-type hypolactasia phenotypes among Euro-Brazilians and Mennonites from South Brazil. Materials and Meth ods: A sequence-specific PCR method to genotype the LCT*-13910C>T polymorphism in 292 Euro-Brazilians and 151 Mennonites (a group with European ancestry and a long history of endogamy) was developed. Using an exact test of population differentiation, the genotype and allele frequency between these and other Brazilian populations were compared. Results: The frequency of -13910*T was significantly higher among the Mennonites when compared to the Euro-Brazilian cohort (0.63 vs. 0.33, p < 0.000001). Accordingly, Mennonites had a higher prevalence of the lactase persistence genotype (88.1 vs. 55.5%, p < 0.000001). The distribution of -13910*T differed between Mennonites and all other Brazilian groups (p < 0.0001). The Euro-Brazilians from Curitiba displayed differences when compared to all other Brazilian groups (p < 0.0001), even to Euro-Brazilians from a different geographic region (p = 0.0003), but were similar to those from Porto Alegre (p = 0.2). Conclusion: Differences in the -13910*T-associated lactase persistence distribution among Euro-Brazilian groups reflect the ancestry and admixture of each particular group and should be considered for adult-type hypolactasia screening.

Mannan-binding lectin (MBL) - associated serine protease 2 (MASP-2) co-activates the lectin pathway of complement in response to several viral infections. The quality of this response partly depends on MASP2 gene polymorphisms, which modulate MASP-2 function and serum levels. In this study we investigated a possible role of MASP2 polymorphisms, MASP-2 serum levels and MBL-mediated complement activation in the susceptibility to HIV/AIDS and HBV/HCV coinfection.A total of 178 HIV patients, 89 (50%) coinfected with HBV/HCV, 51.7% female, average age 40 (12-73) years, and 385 controls were evaluated. MASP-2 levels and MBL-driven complement activation were evaluated by enzyme-linked immunosorbent assay and 11 MASP2 polymorphisms from the promoter to the last exon were haplotyped using multiplex sequence-specific PCR.Genotype distribution was in Hardy-Weinberg equilibrium and differed between HIV+ patients and controls (P=0.030), irrespective of HBV or HCV coinfection. The p.126L variant, which was associated with MASP-2 levels 200ng/mL (OR=5.0 [95%CI=1.3-19.2] P=0.019), increased the susceptibility to HIV infection (OR=5.67 [95%CI=1.75-18.33], P=0.004) and to HIV+HBV+ status (OR=6.44 [95%CI=1.69-24.53, P=0.006). A similar association occurred with the ancient haplotype harboring this variant, AGCDV (OR=2.35 [95%CI=1.31-4.23], P=0.004). On the other hand, p.126L in addition to other variants associated with low MASP-2 levels-p.120G, p.377A and p.439H, presented a protective effect against AIDS (OR=0.25 [95%CI=0.08-0.80], P=0.020), independently of age, sex, hepatic function and viral load. MASP-2 serum levels were lower in HIV+ and HIV+HBV+ patients than in controls (P=0.0004). Among patients, MASP-2 levels were higher in patients with opportunistic diseases (P=0.001) and AIDS (P=0.004). MASP-2 levels correlated positively with MBL/MASP2-mediated C4 deposition (r=0.29, P=0.0002) and negatively with CD4+ cell counts (r=-0.21, P=0.018), being related to decreased CD4+ cell counts (OR=5.8 [95%CI=1.23-27.5, P=0.026).Genetically determined MASP-2 levels seem to have a two-edge effect in HIV and probably HCV/HBV coinfection, whereas low levels increase the susceptibility to infection, but on the other side protects against AIDS.

Hepatitis C virus (HCV) has become a major public health issue and is prevalent in most countries. We examined several MASP2 functional polymorphisms in 104 Brazilian patients with moderate and severe chronic hepatitis C using the primers set to amplify the region encoding the first domain (CUB1), a critical region for the formation of functional mannan-binding lectin (MBL)/MBL-associated serine proteases (MASP)–2 complexes, and the fifth domain (CCP2), which is essential for C4 cleavage of the MASP2 gene. We identified five single nucleotide polymorphisms in patients and controls: p. R99Q, p. D120G, p.P126L, p.D371Y, and p.V377A. Our results show that the p.D371Y variant (c.1111 G > T) is associated with susceptibility to HCV infection (p = 0.003, odds ratio = 6.33, 95% confidence interval = 1.85–21.70). Considered as a dominant function for the T allele, this variant is associated with high plasma levels of the MASP-2 in hepatitis C patients (p < 0.001). However, further functional investigations are necessary to understand the degree of involvement between MASP2 and the HCV susceptibility.

Scarce data are available about the antimicrobial resistance of Group A Streptococcus in South America.This study evaluated the antimicrobial susceptibility profile of 1,112 isolates of Group A Streptococcus during the period from 1993 to 2009 in Curitiba city, Brazil. Macrolide-resistant isolates were characterized by emm typing and pulsed-field gel electrophoresis.All isolates were susceptible to penicillin, vancomycin, and tigecycline. On the contrary, 18.6% of the isolates were resistant to tetracycline, presenting a minimum inhibitory concentration (MIC)(50)/MIC(90) of 32/64 mg/L. Erythromycin resistance rose from 1.9% before 2000 to 4% after 2000 and was associated with a marked increased of MIC levels. Simultaneously, both the phenotype and genotype of macrolide resistance were modified as the M phenotypes (mef(A) genotype) were replaced by the cMLS(B) phenotypes (erm(B) genotype).This polyclonal spreading of cMLS(B) macrolide resistance has not been previously observed in South America and should stimulate further epidemiological surveillance in this part of the world.

Pemphigus is characterized by circulating autoantibodies directed against desmossomal antigens that, once bound to target antigens, induce disruption in the cell-cell adhesion of the epidermis and mucosal epithelium, leading to blister formation. Evidence has indicated a role for complement in the physiopathology of pemphigus, with complement deposition in intercellular spaces of skin and mucous membrane lesions. Mannan-binding lectin (MBL) and Ficolin-2 are recognition proteins of innate immunity, which by binding to specific molecular patterns on pathogens surfaces trigger the activation of complement, leading to phagocytosis and lyses of target cells and inflammation. In this study we report for the first time the deposition of MBL and ficolins in pemphigus lesions. Eight biopsies of skin lesions of pemphigus vulgaris were studied for in situ deposition of IgG and the complement components MBL, Ficolin 1, Ficolin-2, C1q, C3 and membrane attack complex C5b-9. All biopsies presented deposition of IgG and C3 in the intercellular spaces (ICS) of epidermis. MBL deposition was found in the ICS and basal membrane zone (BMZ) of all specimens, whereas C5b-9 showed deposition only in the ICS, with irregular distribution. Ficolin-2 were positive in 50% (4/8) of biopsies showing deposition in the BMZ. On the other hand, ficolin-1 and C1q were negative in all specimens. Our study suggest that MBL and to a lesser extend Ficolin-2 may bind to altered intercellular structures in the skin and lead to the activation of complement in situ, contributing to tissue damage in pemphigus.

Background/Aims: In this study, a clinical and serological follow-up of 8–10 years was performed in relatives of celiac disease (CD) patients from southern Brazil. The occurrence of new CD cases in the families and the use of two different IgA-tTG enzyme-linked immunosorbent assay (ELISA) kits were also evaluated. Methods: Serum samples of 233 relatives, 186 recruited between 1997 and 2000 (phase I) and 138 between 2006 and 2007 (phase II: 91 of the follow-up group and 47 newly tested), were analyzed. As a comparison group, 100 unrelated healthy individuals were evaluated. IgA-EmA was tested by indirect immunofluorescence and IgA-tTG by ELISA. Results: A significant increase in IgA-EmA/IgA-tTG was detected in relatives of patients with CD when compared to controls (p ≤ 0.001). The positivity of antibodies was higher in females (2.4:1 in phase II; p = 0.039), and its high frequency amongst siblings (∼18.81%) highlights the risk of CD in these individuals. The distribution of antibodies by age suggested that CD can occur at any age in relatives, calling attention to the newly tested relatives >60 years of age (p = 0.0657). A better performance of ELISA kits with human tTG was observed. The confirmation of 13 biopsy-proven new CD cases (5.6%; 13/233) at present points out the predisposition to CD in these individuals and the high specificity of concurrently positive antibodies in relatives, especially when both are present in high titers. Conclusion: These results emphasize the familial risk to develop CD and the value of serological screening as an instrument for identifying this disease.

Background Pathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease. Methodology Nine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were measured by qPCR and sCR1 by ELISA, in up to 80 samples. Principal findings Individuals with the most common recombinant haplotype harboring rs3849266*T in intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+ antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p = 0.017). Paucibacillary patients with these variants presented lower sCR1 levels, thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046, respectively). Furthermore, the most ancient haplotype increased susceptibility to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the intronic rs12034383*G allele, which was associated with higher gene expression (p = 0.043), probably increasing internalization of the parasite. Furthermore, there was an inverse correlation between the levels of sCR1 and mannose-binding lectin (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = -0.52, p = 0.007). Conclusions The results lead us to suggest a regulatory role for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis and inflammation., Author summary The reasons for which some individuals resist Mycobacteria leprae infection, whereas others contract leprosy and only a subgroup of them become severely affected, are still poorly understood. The complement receptor 1 (CR1) serves as a gate for bacterial entry in macrophages, but its importance in the spread of infection and emergence of symptoms is unknown. Despite having many common structural and regulatory variants, the CR1 gene was investigated only once in a leprosy association study in Malawi. In order to fill in this gap, we investigated if CR1 polymorphisms are co-responsible for differential disease susceptibility in 213 leprosy patients and 297 controls, also measuring mRNA and soluble CR1 levels. Associations were dependent on specific combinations of variants in regulatory and coding regions, which were also associated with gene and protein expression. Thus, this study corroborates the importance of the CR1 receptor in the susceptibility to leprosy and is the first to bring information about CR1 polymorphisms in the Brazilian population, as well as to show the relationship between genotypes and mRNA and sCR1 levels.

In this study we investigated whether partial or total MASP-2 deficiencies resulting from Asp105Gly mutation are associated with rheumatic fever (RF) and chronic rheumatic heart disease (RHD). The Asp105Gly MASP2 mutation (D105G) was detected by polymerase chain reaction-restriction fragment length polymorphism in 148 patients (43 men and 105 women; mean age 39.1 +/- 14.4 years) with a history of RF, including 106 (73%) with RHD and 42 (27%) without cardiac sequelae, and 129 control subjects (52 men and 77 women, mean age 38.4 +/- 12.2 years). The D105G mutation was detected in four patients with RHD (3.77%) and in five control subjects (3.88%), all in the heterozygous state. None of the patients without cardiac sequelae had the mutation. No significant difference was found in the frequency of the mutant allele between the groups (p0.6). These results suggest that the D105G mutation in the MASP2 gene does not play a major role in the pathogenesis of RF. Whether D105G plays a role in the development of RHD should be ascertained in future studies.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is a cytokine with a potential vaccine adjuvant activity. It is also known that human immunodeficiency virus (HIV) infected patients often show poor immunologic responses to immunization. We examined whether the use of GM-CSF could augment the immunologic response to recombinant vaccine against the hepatitis B virus (HBV) in 80 HIV infected patients (18-35 years old). They received a double dose (40 microg) of recombinant HBV vaccine IM at 0, 1 and 6 months and were randomized to receive either concurrent 20 microg of GM-CSF (n=40) or placebo IM (n=40) with the first vaccine dose. A significant increase in the seroconversion rate was observed after the second vaccine dose in the GM-CSF group (62% GM-CSF versus 30% control group P

The innate immune system is the first line of host defense against infection and is comprised of humoral and cellular mechanisms that recognize potential pathogens within minutes or hours of entry. The effector components of innate immunity include epithelial barriers, phagocytes, and natural killer cells, as well as cytokines and the complement system. Complement plays an important role in the immediate response against microorganisms, including Streptococcus sp. The lectin pathway is one of three pathways by which the complement system can be activated. This pathway is initiated by the binding of mannose-binding lectin (MBL), collectin 11 (CL-K1), and ficolins (Ficolin-1, Ficolin-2, and Ficolin-3) to microbial surface oligosaccharides and acetylated residues, respectively. Upon binding to target molecules, MBL, CL-K1, and ficolins form complexes with MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2), which cleave C4 and C2 forming the C3 convertase (C4b2a). Subsequent activation of complement cascade leads to opsonization, phagocytosis, and lysis of target microorganisms through the formation of the membrane-attack complex. In addition, activation of complement may induce several inflammatory effects, such as expression of adhesion molecules, chemotaxis and activation of leukocytes, release of reactive oxygen species, and secretion of cytokines and chemokines. In this chapter, we review the general aspects of the structure, function, and genetic polymorphism of lectin-pathway components and discuss most recent understanding on the role of the lectin pathway in the predisposition and clinical progression of Rheumatic Fever.

Highlights • MASP-1 and MASP-2 are central players of the lectin pathway of complement. • MASP1 and MASP2 gene polymorphisms regulate protein serum levels and activity. • MASP deficiencies are associated with increased infection susceptibility. • MASP polymorphisms and serum levels are associated with disease progression., The lectin pathway of the complement system has a pivotal role in the defense against infectious organisms. After binding of mannan-binding lectin (MBL), ficolins or collectin 11 to carbohydrates or acetylated residues on pathogen surfaces, dimers of MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2) activate a proteolytic cascade, which culminates in the formation of the membrane attack complex and pathogen lysis. Alternative splicing of the pre-mRNA encoding MASP-1 results in two other products, MASP-3 and MAp44, which regulate activation of the cascade. A similar mechanism allows the gene encoding MASP-2 to produce the truncated MAp19 protein. Polymorphisms in MASP1 and MASP2 genes are associated with protein serum levels and functional activity. Since the first report of a MASP deficiency in 2003, deficiencies in lectin pathway proteins have been associated with recurrent infections and several polymorphisms were associated with the susceptibility or protection to infectious diseases. In this review, we summarize the findings on the role of MASP polymorphisms and serum levels in bacterial, viral and protozoan infectious diseases.

MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF (P=0.02, OR=0.36) and RHD (P=0.01, OR=0.25). In contrast, haplotypes that share the intron 9 - exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD (P=0.02, OR=4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients (P

BackgroundThe gene MASP2 (mannan-binding lectin (MBL)-associated serine protease 2) encodes two proteins, MASP-2 and MAp19 (MBL-associated protein of 19 kDa), bound in plasma to MBL and ficolins. The binding of MBL/MASP-2 and ficolin/MASP-2 complexes to microorganisms activates the lectin pathway of complement and may increase the ingestion of intracellular pathogens such as Mycobacterium leprae.MethodsWe haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 219 Brazilian leprosy patients (131 lepromatous, 29 borderline, 21 tuberculoid, 14 undetermined, 24 unspecified), 405 healthy Brazilians and 291 Danish blood donors with previously determined MASP-2 and MAp19 levels. We also evaluated MASP-2 levels in further 46 leprosy patients and 69 Brazilian controls.ResultsTwo polymorphisms flanking exon 5 of MASP2 were associated with a dominant effect on high MASP-2 levels and an additive effect on low MAp19 levels. Patients presented lower MASP-2 levels (P = 0.0012) than controls. The frequency of the p.126L variant, associated with low MASP-2 levels (below 200 ng/mL), was higher in the patients (P = 0.0002, OR = 4.92), as was the frequency of genotypes with p.126L (P = 0.00006, OR = 5.96). The *1C2-l [AG] haplotype, which harbors p.126L and the deficiency-causing p.439H variant, has a dominant effect on the susceptibility to the disease (P = 0.007, OR = 4.15). Genotypes composed of the *2B1-i and/or *2B2A-i haplotypes, both associated with intermediate MASP-2 levels (200-600 ng/mL), were found to be protective against the disease (P = 0.0014, OR = 0.6). Low MASP-2 levels (P = 0.022), as well as corresponding genotypes with *1C2-l and/or *2A2-l but without *1B1-h or *1B2-h, were more frequent in the lepromatous than in other patients (P = 0.008, OR = 8.8).ConclusionsIn contrast with MBL, low MASP-2 levels increase the susceptibility to leprosy in general and to lepromatous leprosy in particular. MASP2 genotypes and MASP-2 levels might thus be of prognostic value for leprosy progression.

BackgroundPolymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23MBL2haplotypes, associated with enhanced susceptibility to several diseases.ResultsIn this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardizeMBL2studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results.ConclusionUsing extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.

Down syndrome (DS) is the most frequent cause of intellectual disability worldwide. DS individuals present abnormalities in the immune system that include high susceptibility to recurrent infections (RI) as well as to autoimmune diseases. Respiratory tract infections remain one of the major causes of death in DS individuals. Mannan-binding lectin (MBL) functions as an opsonina and initiates the lectin complement pathway. MBL deficiency was shown to increase the susceptibility to different infectious diseases, notably by extracellular pathogens. In the present study, MBL circulating levels were evaluated in 150 children with DS from Brazil, to clarify whether MBL deficiency is associated with the presence of RI in these patients. According to the clinical history 30.7% (46/150) of the DS children experienced RI, and MBL deficiency was seen in 34.8% (16/46) of them compared with 13.5% (14/104) of the DS children without RI (p = 0.005, odds ratio = 3.43, 95% confidence interval = 1.5-7.85). Moreover, MBL deficiency was significantly associated with the occurrence of pneumonia when compared with DS without RI (37.5%, 12/32 vs. 13.5% 14/104, p = 0.005, odds ratio = 3.68, 95% confidence interval = 1.5-6.95). These findings demonstrated that MBL deficiency increases the susceptibility to RI in DS patients and that, in the future, they could potentially benefit from MBL therapy.

BackgroundMannose binding lectin (MBL) has an important role in the activation of the complement system and opsonization of pathogenic microorganisms. Frequent polymorphisms found in theMBL2gene affect the concentration and functionality of the protein and are associated with enhanced susceptibility to severe malaria in African children. MostMBL2typing strategies were designed to the analysis of selected variants, the significance of whole haplotypes is poorly known. In this work, a new typing strategy was developed and validated in an association analysis ofMBL2with adult asymptomatic infection.MethodsMBL2allele-specific fragments of 144 healthy Gabonese adults were amplified by using haplotype-specific sequencing (HSS), a new strategy that combines sequence-specific PCR and sequence-based typing. The Gabonese were investigated for the presence ofPlasmodium falciparumparasitaemia by the amplification of parasite genes, immunochromatographic antigen detection and microscopic analysis. HSS results were also compared with a previously used real-time PCR (RT-PCR) method in 72 Euro-Brazilians.ResultsFourteen polymorphisms were identified beside the commonly investigated promoter (H, L;X, Y;P, Q) and exon 1 (A, O;O=B,CorD) variants. TheMBL2*LYPA/LYPAgenotype was associated with the absence of asymptomatic infection (P = 0.017), whereas theMBL2*LYQChaplotype andYA/YO+YO/YOgenotypes were associated with positive parasite counts in asymptomatic adults (P = 0.033 and 0.018, respectively). The associations were specific toLYPA(identical to the reference sequence Y16577) andLYQC(Y16578) and would not have been revealed by standard genotyping, as there was no association withLYPAandLYQChaplotypes carrying new polymorphisms defined by sequence-based typing. In contrast, HSS and RT-PCR produced very similar results in the less diverse European-derived population.ConclusionIn this work, a new typing strategy for a highly polymorphic gene was developed and validated focusing on the asymptomatic status ofP. falciparum-infected adults. In populations with high nucleotide diversity, it allowed for the identification of associations with fine-scaled haplotypes that would not have been found using common typing techniques. In this preliminary study,MBL2haplotypes or SNPs linked to them were found associated with susceptibility to infection and parasitaemia control of asymptomatic adults.

Rheumatic fever (RF) and its most severe sequela, chronic rheumatic heart disease (CRHD), are mediated by an abnormal immunological host response following a Streptococcus pyogenes oropharyngeal infection. Mannan-binding lectin (MBL), a collectin that activates complement, binds to N-acetylglucosamine, a molecule present on the streptococcus cell wall and on human heart valves. As high levels of MBL and MBL2 associated genotypes have previously been seen to be associated with CRHD, we investigated the association between MBL2 polymorphisms and the presence of acute carditis and arthritis in patients with a history of RF. Polymorphisms in exon 1 and in the X/Y promoter region of the MBL2 gene were determined by PCR-SSP in 149 patients with a history of RF and 147 controls. Genotypes associated with the high production of MBL (YA/YA and YA/XA) were more frequent in the patients with acute (26/35, 74%) and chronic carditis (79/107, 74%) when compared to the controls (79/147, 54%; OR 2.48, 95% CI 1.09-5.67, p=0.035 and OR 2.42, 95% CI 1.41-4.16, p=0.001, respectively). Logistic regression analysis showed that MBL levels >2800ng/ml increased the risk of CRHD (OR 2.91, 95% CI 1.41-6.03, p=0.003). Among the RF patients without cardiac sequela, YA/YA and YA/XA genotypes were significantly associated with acute carditis when compared to the patients without this clinical manifestation (26/28, 93% vs. 9/14, 64%, OR 7.22, 95% CI 1.18-43.98, p=0.031); on the other hand, arthritis was more frequently observed in those patients presenting MBL2 genotypes related to the low production of MBL (10/14, 71% vs. 10/28, 36%; p=0.048, OR 0.22, 95% CI 0.05-0.89). We concluded that MBL2 genotypes associated with the high production of MBL seem to be involved in the pathogenesis of rheumatic carditis and its progression to CRHD.

Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy., Author Summary Chagas disease is considered an important neglected tropical disease, affecting approximately ten million people in Latin America. Although most infected individuals remain asymptomatic, one third of patients develop a chronic heart disease, with progressive inflammation, increase of myocardium, arrhythmia, cardiac insufficiency and heart failure. To date, there is no available marker to indicate the progression neither to determinate the severity of heart damage. Mannan binding lectin (MBL) is an important protein of the immune system able to recognize specific regions on the microorganism surfaces (including Trypanosoma cruzi, the causal agent of Chagas disease) which activate the complement system, a crucial mechanism of the effector immunity. MBL levels and protein activity are affected by genetic differences, named polymorphisms, in the MBL2 gene. This is the first Brazilian study with MBL2 polymorphisms in chronic Chagas disease. We sequenced two regions of MBL2 gene in 196 patients and 202 controls. We found that a polymorphism associated with deficient complement activation protects against Chagas disease and patients with deficiency-associated genotypes presented less echocardiographic alterations. Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings lead us to suggest that genetically determined MBL deficiency plays a protective role against the development and progression of chronic Chagas disease.

The aim of the present study was to investigate a broad spectrum of autoantibodies in patients with endemic pemphigus foliaceus (EPF)—fogo selvagem—and to determine the possible association between EPF and other autoimmune diseases. Indirect immunofluorescence was used to test 120 patients with EPF and 200 healthy controls for the presence of the following autoantibodies: anti-desmoglein-1 (APF), anti-neutrophil cytoplasmic (ANCA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver kidney microsomal (LKM), anti-gastric parietal cells (GPCA) and anti-thyroid microsome (TMA). APF antibodies were detected in 62.5% of the patients (75/120), ANA and SMA in 0.8% (1/120), and TMA in 1.6% (2/120). None of the patients was positive for ANCA, AMA, LKM or GPCA. In the control group, a positivity of 2% was observed for SMA (4/200), 1.5% for TMA (3/200), and 0.5% (1/200) for ANA and GPCA. None of the controls was positive for APF, LKM, AMA or ANCA. The prevalence of the autoantibodies ANA, SMA, AMA, GPCA, LKM and ANCA in patients with EPF was similar to that observed in the control group. No association with clinical or laboratory manifestations of other concomitant autoimmune diseases was observed in EPF patients. These results confirm the concept that EPF is an organ-specific autoimmune disease.

BackgroundMannan-binding lectin-associated serine protease 2 (MASP-2) is a key protein of the lectin pathway of complement. MASP-2 levels have been associated with different polymorphisms within MASP2 gene as well as with the risk for inflammatory disorders and infections. Despite its clinical importance, MASP-2 remains poorly investigated in rheumatoid arthritis (RA).MethodsIn this case-control study, we measured MASP-2 serum levels in 156 RA patients, 44 patient relatives, and 100 controls from Southern Brazil, associating the results with nine MASP2 polymorphisms in all patients, 111 relatives, and 230 controls genotyped with multiplex SSP-PCR.ResultsMASP-2 levels were lower in patients than in controls and relatives (medians 181 vs. 340 or 285 ng/ml, respectively, PConclusionsIn this study, we found the first evidence that MASP-2 deficiency might play an important role in the development of RA and articular symptoms among relatives of RA patients.

Purpose: To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. Methods: Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. Results: A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. Conclusions: Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease. RESUMO Objetivos: Avaliar se as concentrações séricas da lectina ligante de manose da via das lectinas do sistema complemento estão associadas à degeneração macular relacionada à idade. Métodos: Pacientes com degeneração macular relacionada à idade a controles pareados realizaram exame oftalmológico completo e imagens de tomografia de coerência óptica. As concentrações de lectina ligante de manose foram aferidas em amostras de sangue pelo método "time-resolved Immunofluorometric assay". Resultados: Um total de 136 indivíduos foram avaliados incluindo 68 com degeneração macular relacionada à idade (34 exsudativa e 34 não-exsudativa) e 68 controles. Concentrações medianas de lectina ligante de ma-nose foram 608 ng/mL (30-3,415 ng/mL) nos casos e 739 ng/mL (30-6,039 ng/mL) nos controles, não havendo diferença entre os grupos. Comparando degeneração macular relacionada a idade exsudativa (mediana de lectina ligante de manose 476 ng/mL; 30-3,415 ng/mL) e não-exsudativa (692 ng/mL; 30-2,587 ng/mL) também não apresentaram diferença. Conclusões: Concentrações séricas de lectina ligante de manose não estão relacionadas à degeneração macular relacionada a idade ou às formas exsudativa e não-exsudativa.