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Projetos de Pesquisa
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LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 27
  • article 4 Citação(ões) na Scopus
    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 Luana
    Background 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.
  • article 12 Citação(ões) na Scopus
    Duffy null genotype or Fy(a-b-) phenotype are more accurate than self-declared race for diagnosing benign ethnic neutropenia in Brazilian population
  • article 16 Citação(ões) na Scopus
    Diversity of RH and transfusion support in Brazilian sickle cell disease patients with unexplained Rh antibodies
    (2019) DINARDO, Carla L.; KELLY, Shannon; DEZAN, Marcia R.; RIBEIRO, Ingrid H.; CASTILHO, Shirley L.; SCHIMIDT, Luciana C.; VALGUEIRO, Maria do C.; PREISS, Liliana R.; CUSTER, Brian; SABINO, Ester C.; WESTHOFF, Connie M.
    BACKGROUND Genetic diversity in the RH genes among sickle cell disease (SCD) patients is well described but not yet extensively explored in populations of racially diverse origin. Transfusion support is complicated in patients who develop unexpected Rh antibodies. Our goal was to describe RH variation in a large cohort of Brazilian SCD patients exhibiting unexpected Rh antibodies (antibodies against RH antigens to which the patient is phenotypically positive) and to evaluate the impact of using the patient's RH genotype to guide transfusion support. STUDY DESIGN AND METHODS Patients within the Recipient Epidemiology and Evaluation Donor Study (REDS)-III Brazil SCD cohort with unexpected Rh antibodies were selected for study. RHD and RHCE exons and flanking introns were sequenced by targeted next-generation sequencing. RESULTS Fifty-four patients with 64 unexplained Rh antibodies were studied. The majority could not be definitively classified as auto- or alloantibodies using serologic methods. The most common altered RH were RHD*DIIIa and RHD*DAR (RHD locus) and RHCE*ce48C, RHCE*ce733G, and RHCE*ceS (RHCE locus). In 53.1% of the cases (34/64), patients demonstrated only conventional alleles encoding the target antigen: five of 12 anti-D (41.7%), 10 of 12 anti-C (83.3%), 18 of 38 anti-e (47.4%), and one of one anti-E (100%). CONCLUSION RHD variation in this SCD cohort differs from that reported for African Americans, with increased prevalence of RHD*DAR and underrepresentation of the DAU cluster. Many unexplained Rh antibodies were found in patients with conventional RH allele(s) only. RH genotyping was useful to guide transfusion to determine which patients could potentially benefit from receiving RH genotyped donor units.
  • article 2 Citação(ões) na Scopus
    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 Luana
    Background 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.
  • article 4 Citação(ões) na Scopus
    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.
  • article 8 Citação(ões) na Scopus
    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.
  • article 9 Citação(ões) na Scopus
    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 Luana
    BACKGROUNDMolecular 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.
  • article 1 Citação(ões) na Scopus
    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.
  • article 1 Citação(ões) na Scopus
    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.
  • article 2 Citação(ões) na Scopus
    Using droplet digital PCR to screen for rare blood donors: Proof of principle
    (2020) DEZAN, Marcia Regina; PERON, Ana Claudia; OLIVEIRA, Theo Gremen Mimary; OLIVEIR, Valeria Brito; GOMES, Carolina Nunes; SALLES, Nanci A.; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla Luana
    Background: Digital droplet PCR (ddPCR) is a very sensitive high throughput genotyping methodology. To date, the use of ddPCR in immunohematology is restricted to fetal genotyping of red blood cell antigens. Our hypothesis is that this technology could be applied to screen for rare red blood cell genotypes, such as Di(b-). Methods: Nucleic acid of 3168 donors was extracted for viral screening routine in pools of 6, which were converted into three types of 48-donor pools: control pools (only DI*B/*B samples), pools with varying amount of DI*A/*B samples (n = 1-5) and a pool with one rare DI*A/*A sample. Pools were genotyped using ddPCR to detect and quantify DI*A and DI*B alleles. Results: DI*A allele was accurately detected in all pools containing Di(a + b+) samples and in the pool containing one Di(a + b-) sample. No copies were detected in the control pools (n = 60). The ratio between the number of DI*A and DI*B copies varied significantly between the pools and the triplicates. Conclusion: The proposed ddPCR assay was accurate in identifying the rare DI*A allele in large pools of donors and can be applied to screen for Di(b-) phenotype. The strategy can potentially be extended to search for other rare RBC phenotypes.