INGRID HELENA RIBEIRO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- 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.
- 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.
- 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.
- SMIM1 intron 2 gene variations leading to variability in Vel antigen expression among Brazilian blood donors(2019) DEZAN, Marcia Regina; COSTA-NETO, Abel; GOMES, Carolina Nunes; RIBEIRO, Ingrid Helena; OLIVEIRA, Valeria Brito; V, Marina C. A. Conrado; OLIVEIRA, Theo Gremen M.; CARVALHO, Mariana L. P.; ARANHA, Aline Fernanda; BOSI, Silvia R. A.; SALLES, Nanci A.; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; SABINO, Ester Cerdeira; ROCHA, Vanderson; MENDRONE-JUNIOR, Alfredo; DINARDO, Carla Luana; LEVI, Jose EduardoBackground: There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. Methods: Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. Results: SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. Conclusion: The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.
- 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