Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, enviro... more Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations.
Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac dise... more Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac disease. Because limited facilities are available for routine use of anti-transglutaminase antibodies assays in developing countries, a simple, economical immunological test would represent a great step forward in the screening of coeliac disease.
Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NL... more Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NLRP3/CIAS1 genes in inflammatory diseases, and also in the predisposition to autoimmune disorders. We evaluated the possible association of five single nucleotide polymorphisms (SNPs), two in NLRP1 gene and three in NLRP3 gene, in pediatric patients from the north eastern region of Brazil affected by type-1 diabetes (T1D, n = 196), celiac disease (CD, n = 59), and atopic dermatitis (AD, n = 165), and in healthy individuals (n = 192). Our results demonstrated that NLRP3 rs10754558 SNP was associated specifically to T1D (p = 4exp-3) and NLRP3 rs358294199 SNP to CD (p = 5exp-4) in the Brazilian population. Despite its strong association with T1D in Norwegian population, NLRP1 was not associated with T1D, in the Brazilian population. According to previous studies in Caucasoid cohorts, NLRP1 and NLRP3 seemed not to be associated to AD. Since it has been reported that IL-1 beta has a systemic effect in the lost of the immunologic tolerance and that NALP3 inflammasome is directly involved in the production of this pro-inflammatory cytokine, we hypothesized that variations in NLRP3 could belong to a predisposing genetic background that contribute to the development of autoimmune diseases.
Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exo... more Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exon 1 MBL2 allelic variants and the H/L and X/Y promoter variants in 165 children with AD and 165 adult controls and compared them. The 0 allele occurred significantly ...
Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identifie... more Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identified in sugarcane and cloned from genomic sugarcane DNA. The deduced encoded peptide shows the structure and amino acid composition typical of other plant defensins. Using RT-PCR, defensin expression in sugarcane and differences between "normal" and infected sugarcane were evidenced.
Abstract: Patients with an autoimmune condition are known to be at higher risk of developing oth... more Abstract: Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross-sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti-TPO) were determined in all patients and thyroid-stimulating hormone (TSH) levels. The anti-TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti-TPO-positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti-TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti-TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.
Revista Brasileira De Hematologia E Hemoterapia, 2008
As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is ... more As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is significant cross-reactivity. Therefore although detection of HTLV antibodies is characteristic of viral infection, it is not sufficient to confirm the presence of the viral type. Molecular tests used to diagnose the HTLV-I/II viruses are based on investigations of proviral genomic sequences, and allow for an infection to be diagnosed prior to the appearance of any sign or symptom. The HTLV proviral load in infected individuals can be determined using real-time PCR, a faster method with less risk of contamination than simple or nested PCR. We analyzed 63 samples from the Hemope Hospital, of which 33 were from HTLV seropositive individuals and 30 from blood donors, to determine the type of virus and the proviral load. The sensitivity of qualitative PCR in comparison to ELISA was 87.5% (95% IC: 70.1 - 95.9%) and the specificity was 100% (IC 95%: 85.9 - 100.0%). The sensitivity and specificity of real-time PCR in comparison to the serological test (ELISA) were 100% (95% IC: 86.7 - 100.0%) and 96.67% (95% IC: 80.9 - 99.8%) respectively. The proviral load in the seropositive individuals ranged from 13 to 343820 copies/106 PBMC cells. Our study also observed that individuals with TSP/HAM had a higher proviral load than those who showed no symptoms. The use of real time PCR for routine clinical testing of infected individuals will play a significant role in identifying the virus type and determining the proviral load, thereby providing more appropriate treatment.
Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, enviro... more Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations. ᭧
In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms... more In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms (SNPs) in the augmented susceptibility to develop other autoimmune diseases in presence of type 1 diabetes (T1D) in a group of Brazilian patients. Patients were stratified for the presence of autoimmune diseases known to be associated with T1D, such as autoimmune thyroid disease (AITD) and celiac disease (CD), and compared with healthy controls (HC). Our findings suggest that MBL2 functional SNPs are more closely related to AITD than to T1D, being MBL2 SNPs frequencies in T1D patients not affected by AITD comparable to the HC ones, while significantly different between AITD patients and patients not affected by the disease. Thus, the association between MBL2 polymorphisms and T1D that we previously reported, seems to result from the stronger association of MBL2 SNPs with another autoimmune disease, the AITD, frequently associated with T1D.
Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac dise... more Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac disease. Because limited facilities are available for routine use of anti-transglutaminase antibodies assays in developing countries, a simple, economical immunological test would represent a great step forward in the screening of coeliac disease.
Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NL... more Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NLRP3/CIAS1 genes in inflammatory diseases, and also in the predisposition to autoimmune disorders. We evaluated the possible association of five single nucleotide polymorphisms (SNPs), two in NLRP1 gene and three in NLRP3 gene, in pediatric patients from the north eastern region of Brazil affected by type-1 diabetes (T1D, n = 196), celiac disease (CD, n = 59), and atopic dermatitis (AD, n = 165), and in healthy individuals (n = 192). Our results demonstrated that NLRP3 rs10754558 SNP was associated specifically to T1D (p = 4exp-3) and NLRP3 rs358294199 SNP to CD (p = 5exp-4) in the Brazilian population. Despite its strong association with T1D in Norwegian population, NLRP1 was not associated with T1D, in the Brazilian population. According to previous studies in Caucasoid cohorts, NLRP1 and NLRP3 seemed not to be associated to AD. Since it has been reported that IL-1 beta has a systemic effect in the lost of the immunologic tolerance and that NALP3 inflammasome is directly involved in the production of this pro-inflammatory cytokine, we hypothesized that variations in NLRP3 could belong to a predisposing genetic background that contribute to the development of autoimmune diseases.
We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functi... more We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functional polymorphisms in a group of 180 high-risk HPV-infected women and 180 healthy control subjects. The most frequent high-risk HPV genotypes were 16 (47.2%), 31 (11.7%), 33 (5%), and 18 (2.2%), respectively. Of the 180 HPV-infected women, 99 presented with uterine cervical cancer and 81 did not. No differences in MBL2 genotype or in allelic or haplotype frequencies were found between HPV patients who developed cervical uterine cancer and those who did not. When considering combined genotypes grouped according to MBL production (designated as high, low, and deficient producers), we detected a significant difference between healthy controls and high-risk HPV-positive patients, the latter group showing increased frequencies of deficient-producer genotypes (14.4% vs 9.4% in the healthy control group, corrected p ϭ 0.04). In conclusion, a correlation between MBL2 polymorphisms and high-risk HPV infection was found in this study.
Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exo... more Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exon 1 MBL2 allelic variants and the H/L and X/Y promoter variants in 165 children with AD and 165 adult controls and compared them. The 0 allele occurred significantly ...
Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identifie... more Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identified in sugarcane and cloned from genomic sugarcane DNA. The deduced encoded peptide shows the structure and amino acid composition typical of other plant defensins. Using RT-PCR, defensin expression in sugarcane and differences between &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;normal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and infected sugarcane were evidenced.
Dendritic cells (DCs)-based vaccine was demonstrated to increase HIV specific cellular immune res... more Dendritic cells (DCs)-based vaccine was demonstrated to increase HIV specific cellular immune response; however, in some HIV-infected patients, the response to the vaccine resulted to be not effective. In order to understand if the outcome of the vaccination may be influenced by the host's genome and natural immunity, we studied the innate immune genome of HIV-infected patients previously vaccinated with DCs. We identified 15 SNPs potentially associated with the response to the immuno-treatment and two SNPs significantly associated with the modulation of the response to the DC vaccine: MBL2 rs10824792 and NOS1 rs693534. These two SNPs were also studied in different ethnic groups (Brazilians, African and Caucasian) of HIV-infected, exposed uninfected and unexposed uninfected subjects. The HIV positive Caucasian patients were also characterized by different disease progressions. Our findings suggest that, independently and/or in addition to other variables, the host's genome could significantly contribute to the modulation of the response to the DC vaccine.
Abstract: Patients with an autoimmune condition are known to be at higher risk of developing oth... more Abstract: Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross-sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti-TPO) were determined in all patients and thyroid-stimulating hormone (TSH) levels. The anti-TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti-TPO-positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti-TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti-TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.
The aim of this study was to identify in the Brazilian population the frequency of human leukocyt... more The aim of this study was to identify in the Brazilian population the frequency of human leukocyte antigen (HLA) DQ2.5 and DQ8 haplotypes conferring risk for type 1 diabetes (T1D), and to validate a new genotyping method aimed at cost reduction and automation. A total of 184 children and adolescents with T1D and 184 healthy individuals from Recife (northeastern Brazil) were analyzed using the conventional polymerase chain reaction-sequence-specific primers HLA genotyping and a newly described Tag-single-nucleotide polymorphism real-time polymerase chain reaction. The Tag-single-nucleotide polymorphism-based HLA genotyping method was successfully validated, proved to be robust, with limited cost and thus could be successfully used for the identification of genetic susceptibility for T1D in areas with limited financial resources. Our findings report for the first time the distribution of DQ2.5 and DQ8 HLA risk haplotypes associated with T1D in northeastern Brazil and evidence a major risk for developing T1D when the heterozygous DQ2.5/DQ8 or the homozygous DQ2.5/DQ2.5 haplotypes are present. ᭧
Revista Brasileira De Hematologia E Hemoterapia, 2008
As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is ... more As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is significant cross-reactivity. Therefore although detection of HTLV antibodies is characteristic of viral infection, it is not sufficient to confirm the presence of the viral type. Molecular tests used to diagnose the HTLV-I/II viruses are based on investigations of proviral genomic sequences, and allow for an infection to be diagnosed prior to the appearance of any sign or symptom. The HTLV proviral load in infected individuals can be determined using real-time PCR, a faster method with less risk of contamination than simple or nested PCR. We analyzed 63 samples from the Hemope Hospital, of which 33 were from HTLV seropositive individuals and 30 from blood donors, to determine the type of virus and the proviral load. The sensitivity of qualitative PCR in comparison to ELISA was 87.5% (95% IC: 70.1 - 95.9%) and the specificity was 100% (IC 95%: 85.9 - 100.0%). The sensitivity and specificity of real-time PCR in comparison to the serological test (ELISA) were 100% (95% IC: 86.7 - 100.0%) and 96.67% (95% IC: 80.9 - 99.8%) respectively. The proviral load in the seropositive individuals ranged from 13 to 343820 copies/106 PBMC cells. Our study also observed that individuals with TSP/HAM had a higher proviral load than those who showed no symptoms. The use of real time PCR for routine clinical testing of infected individuals will play a significant role in identifying the virus type and determining the proviral load, thereby providing more appropriate treatment.
Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, enviro... more Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations.
Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac dise... more Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac disease. Because limited facilities are available for routine use of anti-transglutaminase antibodies assays in developing countries, a simple, economical immunological test would represent a great step forward in the screening of coeliac disease.
Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NL... more Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NLRP3/CIAS1 genes in inflammatory diseases, and also in the predisposition to autoimmune disorders. We evaluated the possible association of five single nucleotide polymorphisms (SNPs), two in NLRP1 gene and three in NLRP3 gene, in pediatric patients from the north eastern region of Brazil affected by type-1 diabetes (T1D, n = 196), celiac disease (CD, n = 59), and atopic dermatitis (AD, n = 165), and in healthy individuals (n = 192). Our results demonstrated that NLRP3 rs10754558 SNP was associated specifically to T1D (p = 4exp-3) and NLRP3 rs358294199 SNP to CD (p = 5exp-4) in the Brazilian population. Despite its strong association with T1D in Norwegian population, NLRP1 was not associated with T1D, in the Brazilian population. According to previous studies in Caucasoid cohorts, NLRP1 and NLRP3 seemed not to be associated to AD. Since it has been reported that IL-1 beta has a systemic effect in the lost of the immunologic tolerance and that NALP3 inflammasome is directly involved in the production of this pro-inflammatory cytokine, we hypothesized that variations in NLRP3 could belong to a predisposing genetic background that contribute to the development of autoimmune diseases.
Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exo... more Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exon 1 MBL2 allelic variants and the H/L and X/Y promoter variants in 165 children with AD and 165 adult controls and compared them. The 0 allele occurred significantly ...
Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identifie... more Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identified in sugarcane and cloned from genomic sugarcane DNA. The deduced encoded peptide shows the structure and amino acid composition typical of other plant defensins. Using RT-PCR, defensin expression in sugarcane and differences between &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;normal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and infected sugarcane were evidenced.
Abstract: Patients with an autoimmune condition are known to be at higher risk of developing oth... more Abstract: Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross-sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti-TPO) were determined in all patients and thyroid-stimulating hormone (TSH) levels. The anti-TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti-TPO-positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti-TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti-TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.
Revista Brasileira De Hematologia E Hemoterapia, 2008
As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is ... more As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is significant cross-reactivity. Therefore although detection of HTLV antibodies is characteristic of viral infection, it is not sufficient to confirm the presence of the viral type. Molecular tests used to diagnose the HTLV-I/II viruses are based on investigations of proviral genomic sequences, and allow for an infection to be diagnosed prior to the appearance of any sign or symptom. The HTLV proviral load in infected individuals can be determined using real-time PCR, a faster method with less risk of contamination than simple or nested PCR. We analyzed 63 samples from the Hemope Hospital, of which 33 were from HTLV seropositive individuals and 30 from blood donors, to determine the type of virus and the proviral load. The sensitivity of qualitative PCR in comparison to ELISA was 87.5% (95% IC: 70.1 - 95.9%) and the specificity was 100% (IC 95%: 85.9 - 100.0%). The sensitivity and specificity of real-time PCR in comparison to the serological test (ELISA) were 100% (95% IC: 86.7 - 100.0%) and 96.67% (95% IC: 80.9 - 99.8%) respectively. The proviral load in the seropositive individuals ranged from 13 to 343820 copies/106 PBMC cells. Our study also observed that individuals with TSP/HAM had a higher proviral load than those who showed no symptoms. The use of real time PCR for routine clinical testing of infected individuals will play a significant role in identifying the virus type and determining the proviral load, thereby providing more appropriate treatment.
Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, enviro... more Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations. ᭧
In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms... more In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms (SNPs) in the augmented susceptibility to develop other autoimmune diseases in presence of type 1 diabetes (T1D) in a group of Brazilian patients. Patients were stratified for the presence of autoimmune diseases known to be associated with T1D, such as autoimmune thyroid disease (AITD) and celiac disease (CD), and compared with healthy controls (HC). Our findings suggest that MBL2 functional SNPs are more closely related to AITD than to T1D, being MBL2 SNPs frequencies in T1D patients not affected by AITD comparable to the HC ones, while significantly different between AITD patients and patients not affected by the disease. Thus, the association between MBL2 polymorphisms and T1D that we previously reported, seems to result from the stronger association of MBL2 SNPs with another autoimmune disease, the AITD, frequently associated with T1D.
Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac dise... more Background. Anti-transglutaminase antibodies are highly predictive markers of active coeliac disease. Because limited facilities are available for routine use of anti-transglutaminase antibodies assays in developing countries, a simple, economical immunological test would represent a great step forward in the screening of coeliac disease.
Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NL... more Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NLRP3/CIAS1 genes in inflammatory diseases, and also in the predisposition to autoimmune disorders. We evaluated the possible association of five single nucleotide polymorphisms (SNPs), two in NLRP1 gene and three in NLRP3 gene, in pediatric patients from the north eastern region of Brazil affected by type-1 diabetes (T1D, n = 196), celiac disease (CD, n = 59), and atopic dermatitis (AD, n = 165), and in healthy individuals (n = 192). Our results demonstrated that NLRP3 rs10754558 SNP was associated specifically to T1D (p = 4exp-3) and NLRP3 rs358294199 SNP to CD (p = 5exp-4) in the Brazilian population. Despite its strong association with T1D in Norwegian population, NLRP1 was not associated with T1D, in the Brazilian population. According to previous studies in Caucasoid cohorts, NLRP1 and NLRP3 seemed not to be associated to AD. Since it has been reported that IL-1 beta has a systemic effect in the lost of the immunologic tolerance and that NALP3 inflammasome is directly involved in the production of this pro-inflammatory cytokine, we hypothesized that variations in NLRP3 could belong to a predisposing genetic background that contribute to the development of autoimmune diseases.
We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functi... more We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functional polymorphisms in a group of 180 high-risk HPV-infected women and 180 healthy control subjects. The most frequent high-risk HPV genotypes were 16 (47.2%), 31 (11.7%), 33 (5%), and 18 (2.2%), respectively. Of the 180 HPV-infected women, 99 presented with uterine cervical cancer and 81 did not. No differences in MBL2 genotype or in allelic or haplotype frequencies were found between HPV patients who developed cervical uterine cancer and those who did not. When considering combined genotypes grouped according to MBL production (designated as high, low, and deficient producers), we detected a significant difference between healthy controls and high-risk HPV-positive patients, the latter group showing increased frequencies of deficient-producer genotypes (14.4% vs 9.4% in the healthy control group, corrected p ϭ 0.04). In conclusion, a correlation between MBL2 polymorphisms and high-risk HPV infection was found in this study.
Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exo... more Results The results of our analysis are summarized in Table 1 and Table 2. We genotyped the 3 exon 1 MBL2 allelic variants and the H/L and X/Y promoter variants in 165 children with AD and 165 adult controls and compared them. The 0 allele occurred significantly ...
Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identifie... more Comparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identified in sugarcane and cloned from genomic sugarcane DNA. The deduced encoded peptide shows the structure and amino acid composition typical of other plant defensins. Using RT-PCR, defensin expression in sugarcane and differences between &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;normal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and infected sugarcane were evidenced.
Dendritic cells (DCs)-based vaccine was demonstrated to increase HIV specific cellular immune res... more Dendritic cells (DCs)-based vaccine was demonstrated to increase HIV specific cellular immune response; however, in some HIV-infected patients, the response to the vaccine resulted to be not effective. In order to understand if the outcome of the vaccination may be influenced by the host's genome and natural immunity, we studied the innate immune genome of HIV-infected patients previously vaccinated with DCs. We identified 15 SNPs potentially associated with the response to the immuno-treatment and two SNPs significantly associated with the modulation of the response to the DC vaccine: MBL2 rs10824792 and NOS1 rs693534. These two SNPs were also studied in different ethnic groups (Brazilians, African and Caucasian) of HIV-infected, exposed uninfected and unexposed uninfected subjects. The HIV positive Caucasian patients were also characterized by different disease progressions. Our findings suggest that, independently and/or in addition to other variables, the host's genome could significantly contribute to the modulation of the response to the DC vaccine.
Abstract: Patients with an autoimmune condition are known to be at higher risk of developing oth... more Abstract: Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross-sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti-TPO) were determined in all patients and thyroid-stimulating hormone (TSH) levels. The anti-TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti-TPO-positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti-TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti-TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.
The aim of this study was to identify in the Brazilian population the frequency of human leukocyt... more The aim of this study was to identify in the Brazilian population the frequency of human leukocyte antigen (HLA) DQ2.5 and DQ8 haplotypes conferring risk for type 1 diabetes (T1D), and to validate a new genotyping method aimed at cost reduction and automation. A total of 184 children and adolescents with T1D and 184 healthy individuals from Recife (northeastern Brazil) were analyzed using the conventional polymerase chain reaction-sequence-specific primers HLA genotyping and a newly described Tag-single-nucleotide polymorphism real-time polymerase chain reaction. The Tag-single-nucleotide polymorphism-based HLA genotyping method was successfully validated, proved to be robust, with limited cost and thus could be successfully used for the identification of genetic susceptibility for T1D in areas with limited financial resources. Our findings report for the first time the distribution of DQ2.5 and DQ8 HLA risk haplotypes associated with T1D in northeastern Brazil and evidence a major risk for developing T1D when the heterozygous DQ2.5/DQ8 or the homozygous DQ2.5/DQ2.5 haplotypes are present. ᭧
Revista Brasileira De Hematologia E Hemoterapia, 2008
As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is ... more As a high degree of homology exists between the proviral genomes of HTLV-I and HTLV-II, there is significant cross-reactivity. Therefore although detection of HTLV antibodies is characteristic of viral infection, it is not sufficient to confirm the presence of the viral type. Molecular tests used to diagnose the HTLV-I/II viruses are based on investigations of proviral genomic sequences, and allow for an infection to be diagnosed prior to the appearance of any sign or symptom. The HTLV proviral load in infected individuals can be determined using real-time PCR, a faster method with less risk of contamination than simple or nested PCR. We analyzed 63 samples from the Hemope Hospital, of which 33 were from HTLV seropositive individuals and 30 from blood donors, to determine the type of virus and the proviral load. The sensitivity of qualitative PCR in comparison to ELISA was 87.5% (95% IC: 70.1 - 95.9%) and the specificity was 100% (IC 95%: 85.9 - 100.0%). The sensitivity and specificity of real-time PCR in comparison to the serological test (ELISA) were 100% (95% IC: 86.7 - 100.0%) and 96.67% (95% IC: 80.9 - 99.8%) respectively. The proviral load in the seropositive individuals ranged from 13 to 343820 copies/106 PBMC cells. Our study also observed that individuals with TSP/HAM had a higher proviral load than those who showed no symptoms. The use of real time PCR for routine clinical testing of infected individuals will play a significant role in identifying the virus type and determining the proviral load, thereby providing more appropriate treatment.
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