SANDRA FATIMA MENOSI GUALANDRO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
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- Fc gamma R2B B2.4 haplotype predicts increased risk of red blood cell alloimmunization in sickle cell disease patients(2020) COSTA NETO, Abel; SANTOS, Flavia; RIBEIRO, Ingrid; OLIVEIRA, Valeria; DEZAN, Marcia; KASHIMA, Simone; COVAS, Dimas; PEREIRA, Alexandre; FONSECA, Guilherme; MOREIRA, Frederico; KRIEGER, Jose; GUALANDRO, Sandra; ROCHA, Vanderson; MENDRONE JR., Alfredo; DINARDO, Carla L.BACKGROUND Red blood cell (RBC) alloimmunization is an important transfusion complication which is prevalent among sickle cell disease (SCD) patients. Autoimmune diseases are a known risk factor for RBC alloimmunization, suggesting that autoimmunity and post-transfusion alloantibody development occur through similar physiopathological pathways. Polymorphisms in the Fc gamma R2B gene have already been associated with several autoimmune disorders and hypothetically could be associated with RBC alloimmunization. Our goal was to evaluate if important polymorphisms of Fc gamma R2B have an impact on the risk of RBC alloimmunization among SCD patients. STUDY DESIGN AND METHODS This was a case-control study in which alloimmunized and non-alloimmunized SCD patients were compared in terms of the genotype frequency of the Fc gamma R2B polymorphisms -386G/C, -120 T/A, and 695C/T, genotyped through direct Sanger sequencing. RESULTS A total of 237 patients met the eligibility criteria, 120 cases (alloimmunized) and 117 controls (non-alloimmunized). RBC alloimmunization was associated with female sex (p < 0.001), lifetime number of RBC units transfused (p = 0.002) and 120 T/A Fc gamma R2B genotype (p = 0.031). The Fc gamma R2B promoter region haplotype 2B.4 (386C120A) was positively associated with RBC alloimunization (p = 0.045). The logistic regression (LR) model identified female sex (OR 10.03, CI 95% 5.16-19.49; p < 0.001) and Fc gamma R2B 2B.4 haplotype (OR 4.55, CI95% 1.1118.65; p = 0.035) as independent predictors of RBC alloimmunization in SCD patients. CONCLUSION SCD patients with the Fc gamma R2B 2B.4 haplotype had over a fourfold higher risk for RBC alloimmunization. This highlights the role played by Fc gamma R2B on RBC alloimmunization and may be helpful in identifying the immune responders.
- A Polymorphism in Toll-like Receptor 2 Gene Is Associated with Occurrence of Bacterial Infections in Sickle Cell Disease Patients(2018) TOZATTO-MAIO, Karina; GIROT, Robert; LY, Indou Deme; ROCHA, Vanderson; PINTO, Ana Cristina Silva; DIAGNE, Ibrahima; BENZERARA, Yahia; DINARDO, Carla Luana; KASHIMA, Simone; ARAUJO, Itaua Leston; KENZEY, Chantal; FONSECA, Guilherme Henrique Hencklain; RODRIGUES, Evandra; VOLT, Fernanda; JARDULI, Luciana Ribeiro; RUGGERI, Annalisa; MARIASELVAM, Christina Mary; GUALANDRO, Sandra Fatima Menosi; ELAYOUBI, Hanadi; CUNHA, Renato; CAPPELLI, Barbara; SIMOES, Belinda Pinto; GLUCKMAN, Eliane; TAMOUZA, Ryad
- A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease(2019) TOZATTO-MAIO, Karina; GIROT, Robert; LY, Indou D.; ROCHA, Vanderson; PINTO, Ana C. Silva; DIAGNE, Ibrahima; BENZERARA, Yahia; DINARDO, Carla L.; KASHIMA, Simone; LESTON-ARAUJO, Itaua; KENZEY, Chantal; FONSECA, Guilherme H. H.; RODRIGUES, Evandra S.; VOLT, Fernanda; JARDULI, Luciana R.; RUGGERI, Annalisa; MARIASELVAM, Christina M.; GUALANDRO, Sandra F. M.; ELAYOUBI, Hanadi; CUNHA, Renato; CAPPELLI, Barbara; MALMEGRIM, Kelen C. R.; SIMOES, Belinda P.; GLUCKMAN, Eliane; TAMOUZA, RyadDespite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n=430) was divided in two groups: patients who presented at least one episode of bacterial infection (n=235) and patients who never had bacterial infections (n=195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR]=050, 95% confidence interval [CI] 034-075, P<0001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR=318, 95% CI 153-661, P<0001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings.
- Accelerated erythrocyte destruction mimicking post-transfusion hyperhaemolysis in the course of uncomplicated vaso-occlusive crisis associated with sickle cell disease(2020) CONRADO, Marina C. A. V.; FONSECA, Guilherme S. V. C.; DEZAN, Marcia R.; MENDES, Fernanda R.; HAMASAKI, Debora T.; CHINOCA, Karen Z.; FONSECA, Guilherme H.; GUALANDRO, Sandra F. M.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla L.
- Polymorphisms in Inflammatory Genes Modulate Clinical Complications in Patients With Sickle Cell Disease(2020) TOZATTO-MAIO, Karina; GIROT, Robert; LY, Indou Deme; PINTO, Ana Cristina Silva; ROCHA, Vanderson; FERNANDES, Francisco; DIAGNE, Ibrahima; BENZERARA, Yahia; DINARDO, Carla L.; SOLER, Julia Pavan; KASHIMA, Simone; ARAUJO, Itaua Leston; KENZEY, Chantal; FONSECA, Guilherme H. H.; RODRIGUES, Evandra S.; VOLT, Fernanda; JARDULI, Luciana; RUGGERI, Annalisa; MARIASELVAM, Christina; GUALANDRO, Sandra F. M.; RAFII, Hanadi; CAPPELLI, Barbara; NOGUEIRA, Felipe Melo; SCIGLIUOLO, Graziana Maria; GUERINO-CUNHA, Renato Luiz; MALMEGRIM, Kelen Cristina Ribeiro; SIMOES, Belinda P.; GLUCKMAN, Eliane; TAMOUZA, RyadSickle cell disease (SCD), the most common monogenic disease worldwide, is marked by a phenotypic variability that is, to date, only partially understood. Because inflammation plays a major role in SCD pathophysiology, we hypothesized that single nucleotide polymorphisms (SNP) in genes encoding functionally important inflammatory proteins might modulate the occurrence of SCD complications. We assessed the association between 20 SNPs in genes encoding Toll-like receptors (TLR), NK cell receptors (NKG), histocompatibility leukocyte antigens (HLA), major histocompatibility complex class I polypeptide-related sequence A (MICA) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and the occurrence of six SCD clinical complications (stroke, acute chest syndrome (ACS), leg ulcers, cholelithiasis, osteonecrosis, or retinopathy). This study was performed in a cohort of 500 patients. We found that theTLR2 rs4696480TA, TLR2 rs3804099CC, and HLA-G,rs9380142AAgenotypes were more frequent in patients who had fewer complications. Also, in logistic regression, the HLA-Grs9380142Gallele increased the risk of cholelithiasis (AGvs.AA, OR 1.57, 95%CI 1.16-2.15;GGvs.AA, OR 2.47, 95%CI 1.34-4.64;P= 0.02). For SNPs located in theNKG2Dloci, in logistic regression, the A allele in three SNPs was associated with a lower frequency of retinopathy, namely,rs2246809 (AAvs.GG: OR 0.22, 95%CI 0.09-0.50;AGvs.GG: OR 0.47, 95%CI 0.31-0.71;P= 0.004, for patients of same origin),rs2617160 (ATvs.TT: OR 0.67, 95%CI 0.48-0.92;AAvs.TT: OR 0.45, 95%CI 0.23-0.84;P= 0.04), andrs2617169 (AAvs.TT: OR 0.33, 95%CI 0.13-0.82;ATvs.TT: OR 0.58, 95%CI 0.36-0.91,P= 0.049, in patients of same SCD genotype). These results, by uncovering susceptibility to, or protection against SCD complications, might contribute to a better understanding of the inflammatory pathways involved in SCD manifestations and to pave the way for the discovery of biomarkers that predict disease severity, which would improve SCD management.
- RHD and RHCE genotyping by next-generation sequencing is an effective strategy to identify molecular variants within sickle cell disease patients(2017) DEZAN, Marcia R.; RIBEIRO, Ingrid Helena; OLIVEIRA, Valeria B.; VIEIRA, Juliana B.; GOMES, Francisco C.; FRANCO, Lucas A. M.; VARUZZA, Leonardo; RIBEIRO, Roberto; CHINOCA, Karen Ziza; LEVI, Jose Eduardo; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; GUALANDRO, Sandra F. M.; ROCHA, Vanderson G.; MENDRONE-JUNIOR, Alfredo; SABINO, Ester Cerdeira; DINARDO, Carla LuanaBackground: The complexity of Rh genetic variation among sickle cell disease (SCD) patients is high. Conventional molecular assays cannot identify all genetic variants already described for the RH locus as well as foresee novel alleles. Sequencing RHD and RHCE is indicated to broaden the search for Rh genetic variants. Aims: To standardize the Next Generation Sequencing (NGS) strategy to assertively identify Rh genetic variants among SCD patients with serologic suspicion of Rh variants and evaluate if it can improve the transfusion support. Methods: Thirty-five SCD patients with unexplained Rh antibodies were enrolled. A NGS-based strategy was developed to genotype RHD and RHCE using gene-specific primers. Genotype and serological data were compared. Results: Data obtained from the NGS-based assay were gene-specific. Ten and 25 variant RHD and RHCE alleles were identified, respectively. Among all cases of unexplained Rh antibodies, 62% had been inaccurately classified by serological analysis and, of these, 73.1% were considered as relevant, as were associated with increased risk of hemolytic reactions and shortage of units suitable for transfusion. Conclusion: The NGS assay designed to genotype RH coding regions was effective and accurate in identifying variants. The proposed strategy clarified the Rh phenotype of most patients, improving transfusion support.
- Massive autoimmune hemolysis documented by monocyte monolayer assay in a multiply transfused patient using reticulocytes isolated by simple centrifugation in microhematocrit tubes(2018) CONRADO, Marina A.; BONIFACIO, Silvia Leao; NOGUEIRA, Felipe M.; SARAIVA-FILHO, Joao Carlos P.; DEZAN, Marcia Regina; CHINOCA, Karen Z.; GOMES, Francisco; FONSECA, Guilherme H.; GUALANDRO, Sandra F. M.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla Luana
- Two new mutations in the HIF2A gene associated with erythrocytosis(2012) PERCY, Melanie J.; CHUNG, Yu Jin; HARRISON, Claire; MERCIECA, Jane; HOFFBRAND, A. Victor; DINARDO, Carla L.; SANTOS, Paulo C. J. L.; FONSECA, Guilherme H. H.; GUALANDRO, Sandra F. M.; PEREIRA, Alexandre C.; LAPPIN, Terence R. J.; MCMULLIN, Mary Frances; LEE, Frank S.Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen-sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis-associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor-2 alpha (HIF-2 alpha), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met-535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe-540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF-2 alpha with both VHL and PHD2.
- -318C/T polymorphism of the CTLA-4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients(2017) OLIVEIRA, V. B.; DEZAN, M. R.; GOMES, F. C. A.; GUALANDRO, S. F. Menosi; KRIEGER, J. E.; PEREIRA, A. C.; MARSIGLIA, J. D.; LEVI, J. E.; ROCHA, V.; MENDRONE-JUNIOR, A.; SABINO, E. C.; DINARDO, C. L.Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule is expressed on T-lymphocyte membrane and negatively influences the antigen-presenting process. Reduced expression of CTLA-4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post-transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA-4 gene that affect protein expression are associated with RBC alloimmunization. This was a case-control study in which 134 sickle cell disease (SCD) patients and 253 non-SCD patients were included. All patients were genotyped for the polymorphisms 49A/G and -318C/T of CTLA-4 gene. The genotype frequency of -318C/T differed significantly between alloimmunized and nonalloimmunized SCD patients, irrespective of clinical confounders (p=.016). SCD patients heterozygous for -318T allele presented higher risk of alloantibody development (OR: 5.4, CI: 1.15-25.6). In conclusion, the polymorphism -318C/T of CTLA-4 gene is associated with RBC alloimmunization among SCD patients. This highlights the role played by CTLA-4 on post-transfusion alloantibody development.
- FCGR2B B2.4 Haplotype Predicts Increased Risk of Red Blood Cell Alloimmunization in Sickle Cell Disease Patients(2018) NETO, Abel Costa; SANTOS, Flavia Leite; RIBEIRO, Ingrid Helena; OLIVEIRA, Valeria Brito; DEZAN, Marcia Regina; KASHIMA, Simone; COVAS, Dimas Tadeu; PEREIRA, Alexandre Costa; FONSECA, Guilherme Henrique Hencklain; MOREIRA, Frederico; KRIEGER, Jose Eduardo; GUALANDRO, Sandra Fatima Menosi; ROCHA, Vanderson; MENDRONE JR., Alfredo; DINARDO, Carla Luana