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Ankylosing spondylitis (AS) patients may have higher prevalence of mannose-binding lectin (MBL) deficiency than normal individuals. MBL deficiency may influence susceptibility to infections. The aim of the study was to verify if MBL deficiency in patients with AS predisposes to infections. We studied 60 patients with AS diagnosed according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. These patients had their MBL serum levels determinated. Twenty-five individuals were identified as MBL deficient (serum values 100 ng/mL). These patients were paired with 35 "sufficient" MBL producers (median serum level = 700 ng/mL; range 150-4100 ng/mL) for gender, age, use of medications, and tobacco exposure. Medical records of all patients were retrospectively investigated for the period of 5 years and the rate of infection occurrence was compared in the two groups. AS patients with MBL deficiency had higher number of urinary tract infections (p = 0.03; IRR = 2.33; 95% CI = 0.95-6.04) and tuberculosis (p = 0.008; IRR = 9.8; 95% CI = 1.2-441.6) than controls. Regarding tuberculosis infection, one patient (2.8%) in the MBL-sufficient group and six (24.0%) from the deficient group had this infection. The MBL-sufficient patient and five from the deficient group have had latent infections, detected in the screening tests done previous to anti-TNF drug use. The other, in the deficient group, had lung infection while not on anti-TNF treatment. Another patient, from the deficient group, has had tuberculosis skeletal infection in the past. We found a significant association between MBL deficiency and higher risk of tuberculosis and urinary tract infection in patients with AS. More studies with higher number of patients are needed to confirm this finding.

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OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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BACKGROUND: 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. OBJECTIVE: To study the prevalence of MBL deficiency in SpA patients as well as its influence in the clinical profile of these diseases. METHODS: 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. RESULTS: 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; p < 0.0001). 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). CONCLUSION: MBL levels may be linked with the occurrence of SpA but do not influence its phenotype.

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OBJECTIVE: The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. METHODS: Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500µg/L), moderate (<500 and ≥100µg/L) or severe (<100µg/L). RESULTS: SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. CONCLUSION: This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis.

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Abstract Objective The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Methods Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500 µg/L), moderate (<500 and ≥100 µg/L) or severe (<100 µg/L). Results SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. Conclusion This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis.

Resumo Objetivo Vários estudos já investigaram a potencial associação entre a deficiência de lectina de ligação a manose (LLM) e o lúpus eritematoso sistêmico (LES), mas os resultados obtidos são controversos. Uma explicação para esses resultados conflitantes poderia estar nas diferenças étnicas dos indivíduos estudados. Este estudo investigou a associação entre a deficiência de LLM e o LES em uma grande coorte de pacientes brasileiros com LES e controles. Métodos Determinaram-se os níveis séricos de LLM e complemento em 286 pacientes adultos brasileiros com LES e 301 adultos brasileiros saudáveis que atuaram como controles. A deficiência de LLM foi classificada como leve (< 1000 e ≥ 500 µg/L), moderada (< 500 e ≥ 100 µg/L) ou grave (< 100 µg/L). Resultados Os pacientes com LES apresentaram maior frequência de deficiências leve e moderada de LLM em relação aos controles. Os pacientes com LES com deficiência de LLM apresentaram maior frequência de nefrite lúpica em comparação com aqueles sem deficiência de LLM. A deficiência de LLM não esteve associada a qualquer outra manifestação clínica, uso de terapia imunossupressora, atividade da doença, gravidade da doença ou níveis séricos de complemento. Conclusão Este estudo mostra que há uma associação entre a deficiência de LLM e o LES na população brasileira. Encontrou-se também uma associação entre a deficiência de LLM e a nefrite lúpica. Esses resultados apoiam a hipótese de que a deficiência de LLM contribui para o desenvolvimento do LES e da nefrite lúpica.

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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.

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BACKGROUND AND OBJECTIVE: Post-infectious bronchiolitis obliterans (PIBO) is a severe disorder following acute lower pulmonary infection in young children, especially caused by adenovirus. Mannose-binding lectin (MBL) deficiency arising from polymorphisms in the coding and non-coding region on the MBL2 gene has been associated with more frequent and severe respiratory infections. Our aim was to evaluate the influence of MBL variants in the susceptibility and evolution of children with PIBO. METHODS: One hundred eleven children with PIBO diagnosis were studied. The coding A, B, D and X promoter variants of MBL2 gene were assessed by PCR-RFLP. B and D alleles were pooled as O. The combined genotypes A/A and YA/O were grouped as sufficient MBL (sMBL), and O/O and XA/O as insufficient MBL (iMBL) groups. To evaluate the frequency of MBL2 polymorphisms in the general population, we studied DNA samples from 127 healthy donors from the blood bank of the hospital (control group). RESULTS: iMBL variants were significantly more frequent in PIBO children compared with controls (21.6% vs 10.2%, P = 0.01). PIBO patients with iMBL required intensive care unit (P = 0.001) and mechanical assistance at the moment of viral injury (P = 0.001) more frequently than those with sMBL. CONCLUSIONS: Insufficiency of MBL was more common in PIBO children than in healthy controls. This genetic condition was significantly associated with more severe initial disease, illustrating the relevance of innate immune defence factors prior to the maturation of the adaptative immune system.

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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...

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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.

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We describe an 11 month old girl with mannose-binding lectin deficiency who presented with recurrent infections. Her mother and brother also were affected. Mannose-binding deficiency is common, and we suggest that testing for it should be included in the evaluation of children with increased susceptibility to infection.

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The association of Down syndrome with mannose-binding lectin (MBL)-deficiency, recurrent infections and vasculitis has not been reported. We report a 30 year-old female with Down-syndrome associated with MBL-deficiency with the genotype LXA/HYD, IgG-deficiency, recurrent uro-genital infections, cutaneous vasculitis, G20.210A prothrombin mutation, deep venous thrombosis, and pulmonary embolism. MBL-deficiency in combination with IgG deficiency might have favored the development of recurrent uro-genital infections. Immunodeficiency might be also involved in the pathogenesis of cutaneous vasculitis. Deep venous thrombosis and pulmonary embolism were attributed to the genetically determined prothrombotic state and intake of oral contraceptives.

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The association of Down syndrome with mannose-binding lectin (MBL)-deficiency, recurrent infections and vasculitis has not been reponed. We repon a 30 year-old female with Down-syndrome associated with MBL-deficiency with the genotype LXA/HYD, IgG-deficiency, recurrent uro-genital infections, cutaneous vasculitis, G20.210A prothrombin mutation, deep venous thrombosis, and pulmonary embolism. MBL-deficiency in combination with IgG deficiency might have favored the development of recurrent uro-genital infections. Immunodeficiency might be also involved in the pathogenesis of cutaneous vasculitis. Deep venous thrombosis and pulmonary embolism were attributed to the genetically determined prothrombotic state and intake of oral contraceptives.

La asociación de síndrome de Down con deficiencia de lectina de unión a manosa, infecciones recurrentes y vasculitis no ha sido informada. Presentamos una mujer de 30 años de edad con síndrome de Down asociado a deficiencia de lectina de unión a mañosa, con el genotipo LXA/HYD, deficiencia de IgG, infecciones urogenitales recurrentes, vasculitis cutánea, mutación de protrombina G20.210A, trombosis venosa profunda y embolia pulmonar. La deficiencia de lectina de unión a manosa combinada con la deficiencia de IgG puede haber favorecido las infecciones urogenitales recurrentes. La inmunodeficiencia puede también tener relación con la patogenia de la vasculitis cutánea. La trombosis venosa profunda y la embolia pulmonar pueden deberse al estado protrombótico derivado de la mutación de protrombina y el uso de contraceptivos orales.

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Mannan-binding lectin (MBL) is an important component of the first-line defence against infections. Evidence has shown that MBL deficiency, reducing phagocytosis and internalization of intracellular pathogens may protect the host against intracellular infections such as leprosy. In this study, we speculated whether genetically determined low MBL serum levels confer protection against Mycobacterium leprae infection. One hundred and ninety-one patients with leprosy, presenting lepromatous (n = 118), tuberculoid (n = 31), dimorph (n = 30) and indeterminate (n = 12) clinical forms and 110 healthy controls matched with the patients according to sex, age and ethnic background were investigated. MBL concentrations were measured in a double-antibody enzyme immune assay and C-reactive protein (CRP) serum levels by nephelometry. A significant negative association of MBL low values (< 100 ng/ml) was observed with lepromatous patients when comparing with controls and tuberculoid patients [10/118, 8.47%versus 21/110, 19.09%P = 0.03 chi(2) with Yates' correction, odds ratio (OR) 0.39, confidence interval (CI) 0.18-0.88 and 8/31, 25.81%, P = 0.02, OR 0.27, CI 0.09-0.75, respectively]. There was no significant difference in the distribution of MBL levels between patients and controls or among the clinical forms. The concentration of CRP was significantly increased in the patients (P = 0.0002) and in the lepromatous form (P = 0.0001) when compared to controls. A weak positive correlation between MBL and CRP levels was observed in the patients (P = 0.010, R = 0.255). These data suggest a protective role for MBL deficiency against the development of the most severe and multi-bacillary form of leprosy.

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BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune response and binds microbial surfaces through carbohydrate recognition domains. MBL deficiency may contribute to susceptibility to a variety of infectious diseases, particularly in young children. MBL binds to the Cryptosporidium sporozoite and may be important in resistance to cryptosporidiosis. METHODS: We studied the association of serum MBL levels and cryptosporidiosis in a case-control study of young Haitian children with cryptosporidiosis versus children who were control subjects. RESULTS: Ninety-nine children were enrolled, as follows: 49 children with cryptosporidiosis, 41 healthy controls, and 9 children with diarrhea from other causes. Case children were more malnourished than controls, and 49% had persistent or chronic diarrhea. At enrollment, mean serum MBL levels were markedly lower in children with cryptosporidiosis (P = .002), as was the number of children with an MBL deficiency of < or = 70 ng/mL (P = .005). In multivariate analysis, the association of cryptosporidiosis and MBL deficiency persisted (P = .002; adjusted odds ratio, 22.4), as did the association of cryptosporidiosis with general malnutrition. The subset of children with cryptosporidiosis and MBL deficiency were more likely to be male (P = .025). CONCLUSIONS: MBL may be an important component of innate immune protection against Cryptosporidium infection in young children. Additional studies are necessary to determine whether MBL intestinal losses, deficient epithelial expression, and/or genetic polymorphisms in the MBL gene contribute to MBL deficiency in cryptosporidiosis and other enteric infections in young children.

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OBJECTIVE: To characterize an IgA deficient population in terms of the incidence of IgG subclass and mannose-binding lectin (MBL) deficiencies and the type and severity of infections and other associated disorders. BACKGROUND: Selective IgA deficiency is probably the commonest of the primary immunodeficiency disorders and although it may lead to an increased risk for respiratory and gastrointestinal infections and associated to various autoimmune diseases, it may also be asymptomatic. Several studies have suggested the need of a concomitant defect in order for manifestation of its symptoms. METHODS: A total of 27 patients fulfilling the diagnostic criteria of selective IgA deficiency were evaluated for IgG subclass and MBL deficiencies after a thorough medical history, physical examination and pertinent evaluation for concomitant medical conditions. RESULTS: The overall incidence of IgG subclass deficiency found in the IgA deficient group was 18.5%. MBL deficiency was found to be 3.7%. These frequencies may have been influenced by the age group evaluated and the size of the population studied. Severe infections were more common in patients with combined deficiencies, either IgA and any of the IgG subclasses or IgA and MBL deficiency. Atopy was widely represented in the patients studied. CONCLUSIONS: The observed relationship between combined deficiencies Ig A, IgG subclasses and MBL and the increased representation of severe infections needs to be corroborated in a larger sample of patients with an inclusion of pediatric patients.

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OBJECTIVE: To characterize an IgA deficient population in terms of the incidence of IgG subclass and mannose-binding lectin (MBL) deficiencies and the type and severity of infections and other associated disorders. BACKGROUND: Selective IgA deficiency is probably the commonest of the primary immunodeficiency disorders and although it may lead to an increased risk for respiratory and gastrointestinal infections and associated to various autoimmune diseases, it may also be asymptomatic. Several studies have suggested the need of a concomitant defect in order for manifestation of its symptoms. METHODS: A total of 27 patients fulfilling the diagnostic criteria of selective IgA deficiency were evaluated for IgG subclass and MBL deficiencies after a thorough medical history, physical examination and pertinent evaluation for concomitant medical conditions. RESULTS: The overall incidence of IgG subclass deficiency found in the IgA deficient group was 18.5. MBL deficiency was found to be 3.7. These frequencies may have been influenced by the age group evaluated and the size of the population studied. Severe infections were more common in patients with combined deficiencies, either IgA and any of the IgG subclasses or IgA and MBL deficiency. Atopy was widely represented in the patients studied. CONCLUSIONS: The observed relationship between combined deficiencies Ig A, IgG subclasses and MBL and the increased representation of severe infections needs to be corroborated in a larger sample of patients with an inclusion of pediatric patients.

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