VANDERSON GERALDO ROCHA
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 - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
31 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 31
- Prevalence and laboratorial determinants of the clinical relevance of antibodies of undetermined specificity(2019) CONRADO, Marina Cavalcanti de Albuquerque da Veiga; CARDOSO, Regina A.; DEZAN, Marcia Regina; OLIVEIRA, Valeria Brito; NETO, Abel da Costa; ZIZA, Karen Chinoca; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; SABINO, Ester Cerdeira; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla LuanaBackground and Objectives Antibodies of unknown specificity (AUS) are frequently identified in the pre-transfusion testing. These antibodies can be insignificant or potentially cause post-transfusion haemolysis. Information about the prevalence of clinically relevant AUS is still lacking. Our aim was to predict the potential clinical relevance of AUS using the monocyte monolayer assay (MMA) and to identify the clinical and laboratorial determinants of AUS' significance. Materials and Methods Antibodies of unknown specificity identified at a single institution from 2015-2017 were evaluated through MMA. A monocyte index (MI) of more than 5% was predictive of potential post-transfusion haemolysis. Results Thirty-two patients with AUS were included in the study. Of the studied AUS, 37 center dot 5% (12/32) presented with a monocyte index (MI) more than 5%. In the group of significant AUS, 41 center dot 7% of the patients presented with sickle cell disease (SCD) and the AUS were associated with Rh antibodies in 75% of the cases. In the group of insignificant AUS, only 10% of the patients had SCD and the association with Rh antibodies was detected in 20% of the cases. The presence of Rh antibodies was independently associated with the AUS clinical relevance (P = 0 center dot 012). Conclusion More than one-third of the AUS are potentially clinically relevant, and the association with Rh antibodies is predictive of AUS relevance. Services must honour AUS in the pre-transfusion process in order to ensure transfusion safety.
- Duffy null genotype or Fy(a-b-) phenotype are more accurate than self-declared race for diagnosing benign ethnic neutropenia in Brazilian population(2017) DINARDO, C. L.; KERBAUY, M. N.; SANTOS, T. C.; LIMA, W. M.; DEZAN, M. R.; OLIVEIRA, V. B.; MENDRONE-JUNIOR, A.; ROCHA, V.; VELLOSO, E. D. R. P.
- Variant genotypes associated with reduced expression of RhCE antigens among Brazilian blood donors(2021) DEZAN, Marcia Regina; OLIVEIRA, Valeria B.; CONRADO, Marina C. A. V.; ROCHA, Mateus Cardoso da; LUZ, Fabio; GALLUCCI, Antonio; PEREIRA, Alexandre C.; KRIEGER, Jose E.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla LuanaBackground The genetic diversity of the RHCE gene locus has been explored in diverse populations of different racial backgrounds. Data referring to the diversity of RHCE encoding weakened expression of C, c, E, and e in multiethnic populations is still incomplete. Methods Samples from Brazilian blood donors presenting reduced expression of C, c, E, or e on gel method were selected for the study. All exons and flanking introns of RHCE were genotyped though direct Sanger sequencing for the included donors. Results Sixty-six donors were included: 23 with weak C, 22 with weak c, 6 with weak E, 14 with weak e, and 1 with weak c and E. Among the samples with weak C, the following altered RH*C were encountered: RHCE*CeMA (n = 3), RHCE*Ce941C (n = 1), and RHCE*CeVA (n = 1). RHD*D-CE(4-7)-D was detected in six cases, RHCE*CE was presumably present in five cases, and seven cases were unexplained. Two altered alleles underlay the weak c phenotype: RHCE*ceJAL (n = 20) and RHCE*ce340T (n = 2), and two altered RHCE justified weak e: RHCE*ceMO (n = 6) and RHCE*ceJAL (n = 8). Three variant RHCE were associated with weak E: RHCE*cEJU (n = 4), RHCE*cE382C (n = 1), and RHCE*cEIV (n = 1). The RHCE*cE905A justified one case of weak c and E. Conclusion We describe the distribution of RHCE variants found in association with weak expression of C, c, E, and e in blood donors of multiethnic origin, which differs in comparison to that previously reported for people of African or Caucasian descent.
- 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.
- Defining the clinical relevance of red blood cell autoantibodies by Monocyte Monolayer Assay(2018) CONRADO, Marina C. A. V.; D'AVILA, Amanda N.; VIEIRA, Juliana B.; BONIFACIO, Silvia L.; GOMES, Francisco C. A.; DEZAN, Marcia R.; OLIVEIRA, Valeria B.; RIBEIRO, Ingrid H.; TUCUNDUVA, Luciana T. C. M.; MENDRONE-JUNIOR, Alfredo; ROCHA, Vanderson; DINARDO, Carla L.BackgroundThe Monocyte Monolayer Assay (MMA) is an in vitro simulation of red blood cell (RBC) alloantibody behavior. It has been classically applied to predict the risks of post-transfusion hemolytic reactions when transfusing incompatible RBC units. Quantifying erythrophagocytosis by MMA may be an interesting option for situations where there is doubt whether a RBC autoantibody is mediating significant hemolysis. Here, we present three situations involving RBC autoantibodies in which the MMA was decisive for clarifying the diagnosis and choosing the best clinical treatment. Case ReportCase 1. Pregnant patient with severely anemic fetus exhibited warm autoantibody without signs of hemolysis. MMA revealed 30% of monocyte index (MI) highlighting that fetal hemolysis was caused by maternal autoantibody. Prednisone was prescribed with fetal clinical improvement. Cases 2 and 3. Two patients with the diagnosis of mixed auto-immune hemolytic anemia and poor response to corticosteroids were evaluated using MMA. The resulting MI was less than 10% in both cases, suggesting that the cold-agglutinin rather than the warm auto-IgG was responsible for overt hemolysis. Treatment with rituximab was begun, with good clinical response. ConclusionMMA can be used to evaluate the ability of RBC autoantibodies to mediate overt hemolysis. It can be especially useful to determine the role played by cold and warm auto-antibodies in mixed auto-immune hemolytic disease, helping to define the best treatment option.
- 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.
- Evaluation of the applicability and effectiveness of a molecular strategy for identifying weakD and DEL phenotype among D- blood donors of mixed origin exhibiting high frequency of RHD*(2018) DEZAN, Marcia Regina; GUARDALINI, Luis Giovani O.; PESSOA, Elaine; RIBEIRO, Ingrid Helena; OLIVEIRA, Valeria Brito; LUZ, Fabio; NOVAC, Denise Rossite; GALLUCCI, Antonio; BONIFACIO, Silvia; GOMES, Francisco; LEVI, Jose E.; PEREIRA, Alexandre C.; KRIEGER, Jose E.; MENDRONE-JUNIOR, Alfredo; ROCHA, Vanderson; DINARDO, Carla LuanaBACKGROUNDMolecular tests designed to detect the presence of active RHD gene among D- donors have been successfully applied in people of European ancestry, but not in admixed populations with a considerable frequency of RHD*. Our goal was to evaluate the performance of a molecular screening tool for identifying active RHD alleles among Brazilian blood donors classified as D- C+ and/or E+. STUDY DESIGN AND METHODSPools of five DNA samples of serologically D- C+ and/or E+ donors were checked by a RHD polymerase chain reaction (PCR) assay specific for RHD Intron 4 and Exon 7. When a pool result was positive, samples were genotyped individually for RHD Intron 4 and Exon 7, RHD*, RHCE*Cc, and RHD zygosity. Donors suspected of active RHD gene were further evaluated by whole-coding region and flanking intron direct sequencing. RESULTSA total of 405 donors were included. Two percent exhibited active RHD gene, codifying D-weak (38 and 45) or DEL phenotype. The most prevalent DEL allele was RHD*DEL1 (c.1227G>A), which is proven to be immunogenic. A high frequency of RHD* was detected in the donors with nondeleted RHD alleles (31%), far superior to the frequency of RHD variant alleles (15.5%). The proposed approach presented sensitivity of 100% and specificity of 85.7% for identifying active RHD gene. CONCLUSIONThe strategy of checking D- donors with RHD PCR followed by exclusion of RHD* allele has proved efficient in identifying weak-D and DEL phenotype in the Brazilian population.
- Prevalence of SMIM1 c.64_80del17 homozygotes in southeastern Brazil: the Vel-negative phenotype(2019) DEZAN, Marcia R.; DINARDO, Carla L.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; LEVI, Jose E.
- How Ancestry Influences the Chances of Finding Unrelated Donors: An Investigation in Admixed Brazilians(2020) NUNES, Kelly; AGUIAR, Vitor R. C.; SILVA, Marcio; SENA, Alexandre C.; OLIVEIRA, Danielli C. M. de; DINARDO, Carla L.; KEHDY, Fernanda S. G.; TARAZONA-SANTOS, Eduardo; ROCHA, Vanderson G.; CARNEIRO-PROIETTI, Anna Barbara F.; LOUREIRO, Paula; FLOR-PARK, Miriam V.; MAXIMO, Claudia; KELLY, Shannon; CUSTER, Brian; WEIR, Bruce S.; SABINO, Ester C.; PORTO, Luis Cristovao; MEYER, DiogoA match of HLA loci between patients and donors is critical for successful hematopoietic stem cell transplantation. However, the extreme polymorphism of HLA loci - an outcome of millions of years of natural selection - reduces the chances that two individuals will carry identical combinations of multilocus HLA genotypes. Further, HLA variability is not homogeneously distributed throughout the world: African populations on average have greater variability than non-Africans, reducing the chances that two unrelated African individuals are HLA identical. Here, we explore how self-identification (often equated with ""ethnicity"" or ""race"") and genetic ancestry are related to the chances of finding HLA compatible donors in a large sample from Brazil, a highly admixed country. We query REDOME, Brazil's Bone Marrow Registry, and investigate how different criteria for identifying ancestry influence the chances of finding a match. We find that individuals who self-identify as ""Black"" and ""Mixed"" on average have lower chances of finding matches than those who self-identify as ""White"" (up to 57% reduction). We next show that an individual's African genetic ancestry, estimated using molecular markers and quantified as the proportion of an individual's genome that traces its ancestry to Africa, is strongly associated with reduced chances of finding a match (up to 60% reduction). Finally, we document that the strongest reduction in chances of finding a match is associated with having an MHC region of exclusively African ancestry (up to 75% reduction). We apply our findings to a specific condition, for which there is a clinical indication for transplantation: sickle-cell disease. We show that the increased African ancestry in patients with this disease leads to reduced chances of finding a match, when compared to the remainder of the sample, without the condition. Our results underscore the influence of ancestry on chances of finding compatible HLA matches, and indicate that efforts guided to increasing the African component of registries are necessary.