Margareth Torres

Antibody-mediated rejection (AMR) after pancreas and pancreas-kidney transplantation.

Antibody‐mediated rejection (AMR) requires specific diagnostic tools and treatment and is associated with lower graft survival. We prospectively screened C4d in pancreas (n = 35, in 27 patients) and kidney (n = 33, in 21 patients) for cause biopsies. Serum amylase and lipase, amylasuria, fasting blood glucose (FBG) and 2‐h capillary glucose (CG) were also analysed. We found that 27.3% of kidney biopsies and 43% of pancreatic biopsies showed C4d staining (66.7% and 53.3% diffuse in peritubular and interacinar capillaries respectively). Isolated exocrine dysfunction was the main indication for pancreas biopsy (54.3%) and was followed by both exocrine and endocrine dysfunctions (37.1%) and isolated endocrine dysfunction (8.6%). Laboratorial parameters were comparable between T‐cell mediated rejection and AMR: amylase 151.5 vs. 149 U/l (P = 0.075), lipase 1120 vs. 1288.5 U/l (P = 0.83), amylasuria variation 46.5 vs. 61% (P = 0.97), FBG 69 vs. 97 mg/dl (P = 0.20) and 2‐h CG maximum 149.5 vs. 197.5 mg/dl (P = 0.49) respectively. Amylasuria values after treatment correlated with pancreas allograft loss (P = 0.015). These data suggest that C4d staining should be routinely investigated when pancreas allograft dysfunction is present because of its high detection rate in cases of rejection.

A bioinformatics approach to ascertaining the rarity of HLA alleles

A project of the 15th International Histocompatibility Workshop examined the rarity of human leukocyte antigen (HLA) alleles. A section was constructed in the website, www.allelefrequencies.net to contain this data from different sources. A mechanism to search the data was implemented for use by any individual.

HLA imputation in an admixed population: An assessment of the 1000 Genomes data as a training set.

Methods to impute HLA alleles based on dense single nucleotide polymorphism (SNP) data provide a valuable resource to association studies and evolutionary investigation of the MHC region. The availability of appropriate training sets is critical to the accuracy of HLA imputation, and the inclusion of samples with various ancestries is an important pre-requisite in studies of admixed populations. We assess the accuracy of HLA imputation using 1000 Genomes Project data as a training set, applying it to a highly admixed Brazilian population, the Quilombos from the state of São Paulo. To assess accuracy, we compared imputed and experimentally determined genotypes for 146 samples at 4 HLA classical loci. We found imputation accuracies of 82.9%, 81.8%, 94.8% and 86.6% for HLA-A, -B, -C and -DRB1 respectively (two-field resolution). Accuracies were improved when we included a subset of Quilombo individuals in the training set. We conclude that the 1000 Genomes data is a valuable resource for construction of training sets due to the diversity of ancestries and the potential for a large overlap of SNPs with the target population. We also show that tailoring training sets to features of the target population substantially enhances imputation accuracy.

Transplante de sangue de cordão umbilical - SCU

The frequent use of umbilical cord blood as the source of hematopoietic stem cells, both in children and adults who do not have related donors, has led to the establishment of a better standardization of selection criteria aiming at improving the results. The choice of the umbilical cord blood unit should be based on the total number of nucleated cells and the number of differences in the human leukocyte antigen (HLA) system. When a unit has minimal cellularity, the use of a double cord blood transplant should be considered. When two or more units have similar characteristics, the choice may be determined by the CD34 count, ABO compatibility and the quality and speed to obtain the unit.

Seleção de doador de medula óssea ou sangue periférico

A compatibilidade HLA e o fator mais valorizado na escolha do doador de medula ossea voluntario, preconizando-se a realizacao de HLA de alta resolucao nos locos HLA-A,B,C, DRB1 e DQB1. Tem sido dado preferencia para o doador com consanguinidade alelica 8x8 (A,B,C, DRB1). Na presenca de incompatibilidade na classe-I sugere-se a busca de doador com compatibilidade DQB1 (9x10). Ja as incompatibilidades dos locos DPB1 nao constituem criterio de exclusao de doador, exceto quando existir presenca de anticorpo contra o loco HLA-DP do doador.

Population variation of HLA genes in rural communities in Brazil, the Quilombos from the Vale do Ribeira, São Paulo – Brazil

In the present study, we characterized the allelic and haplotypic profile of the genes HLA-A, -B, -C and -DRB1 (PCR-SBT) in a population sample of 144 highly admixed individuals, coming from rural communities in Brazil (Quilombos from Vale do Ribeira, in the State of São Paulo). Furthermore, we identified three individuals with a new null allele in the HLA-C gene (HLA-C(∗)02:105N), associated with the haplotype HLA-A(∗)80: 01∼B(∗)18: 01:01G∼DRB1(∗) 07:01.

Induction of platelet refractoriness after myeloablative unrelated allogeneic hematopoietic peripheral blood progenitor cell transplant from HLA-sensitized female donor.

enterocolitis: a meta-analysis of observational data. Pediatrics 2012;129:529-40. 3. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316. 4. van Imhoff DE, Dijk PH, Hulzebos CV; BARTrial study group, Netherlands Neonatal Research Network. Uniform treatment thresholds for hyperbilirubinemia in preterm infants: background and synopsis of a national guideline. Early Hum Dev 2011;87:521-5.

Seleção de doador não aparentado

Apesar da presenca de anticorpos anti-HLA em transplantes de orgaos solidos estar associada a rejeicao, essa correlacao nao havia sido pesquisada em transplante alogenico de celulas progenitoras hematopoeticas (TCPH). Estudos mais recentes na literatura tem demonstrado que a falencia da enxertia no TCPH pode ser mediada por aloanticorpos anti-HLA doador especifico (DSA). A especificidade desses anticorpos pode ser evidenciada pelas tecnicas de fase solida, onde os antigenos HLA unicos sao aderidos a perolas de poliestireno, que permite a realizacao da prova cruzada virtual. Na presenca de DSA, e recomendavel selecionar outro doador ou realizar as estrategias de remocao dos anticorpos.

Determination of an unrelated donor pool size for human leukocyte antigen-matched platelets in Brazil

Background Successful transfusion of platelet refractory patients is a challenge. Many potential donors are needed to sustain human leukocyte antigen matched-platelet transfusion programs because of the different types of antigens and the constant needs of these patients. For a highly mixed population such as the Brazilian population, the pool size required to provide adequate platelet support is unknown. Methods A mathematical model was created to estimate the appropriate size of an unrelated donor pool to provide human leukocyte antigen-compatible platelet support for a Brazilian population. A group of 154 hematologic human leukocyte antigen-typed patients was used as the potential patient population and a database of 65,500 human leukocyte antigen-typed bone marrow registered donors was used as the donor population. Platelet compatibility was based on the grading system of Duquesnoy. Results Using the mathematical model, a pool containing 31,940, 1710 and 321 donors would be necessary to match more than 80% of the patients with at least five completely compatible (no cross-reactive group), partial compatible (one cross-reactive group) or less compatible (two cross-reactive group) donors, respectively. Conclusion The phenotypic diversity of the Brazilian population has probably made it more difficulty to find completely compatible donors. However, this heterogeneity seems to have facilitated finding donors when cross-reactive groups are accepted as proposed by the grading system of Duquesnoy. The results of this study may help to establish unrelated human leukocyte antigen-compatible platelet transfusions, a procedure not routinely performed in most Brazilian transfusion services.

Eosinophil chimerism in the differential diagnosis between DEK-NUP214-positive acute myeloid leukaemia relapse and chronic graft-versus-host disease

Eosinophilia is a rare, recurrent finding in acute myeloid leukaemia (AML). The classic cases include core-binding factor AMLs with chromosome 16 abnormalities and AMLs with rearrangements of the platelet derived growth factor (PDGF) receptor A and B genes ( PDGFRA and PDGFRB ) and the fibroblast growth factor receptor 1 gene ( FGFR1 ). AML with t(6;9)(p23;q24) is a rare entity (0.7%–1.8% of all AMLs), characterised by multilineage dysplasia, basophilia and an unfavourable prognosis.1–3 This cytogenetic alteration leads to the formation of the DEK-NUP214 hybrid protein, and usually presents as a single abnormality, but it can also be associated with a complex karyotype.4 There are currently no descriptions of eosinophilia associated with DEK-NUP214+ AML. We report the case of a 16-year-old male patient who presented with generalised cutaneous pruritus and fever, associated with peripheral blood eosinophilia (absolute count 7830 cells/μL) in August 2010. After ruling out common causes of secondary eosinophilia, the patient was submitted to bone marrow aspiration, which showed erythroid hyperplasia (58.8%) with dyserythropoiesis, eosinophilia (16.4%), dysgranulopoiesis and 9.6% blast cells. These findings were compatible with the diagnosis of AML-M6, according to the French–American–British classification. A cytogenetic study showed the presence of t(6;9) (p23;q34) as the sole anomaly. Fluorescence in-situ hybridisation (FISH) was negative for inv(16), and molecular studies showed wild-type sequences for the fms-related tyrosine kinase 3 ( FLT3 ) and nucleophosmin ( NPM1 ). FISH was also negative for PDGFRA rearrangement. The patient was treated with two cycles of cytarabine-based chemotherapy, achieving haematological remission; nevertheless, peripheral …