Molecular studies reveal a concordant KEL genotyping between patients with hemoglobinopathies and blood donors in Sao Paulo City, Brazil

Boturão‐Neto, Edmir; Chiba, Akemi Kuroda; Vicari, Perla; Figueiredo, Maria Stella; Bordin, José Orlando

doi:10.3324/haematol.12766

Cited by 4 publications

(4 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have suggested at least in SCD patients, that genetic makeup is very relevant to the development of antibodies mainly altered Rh or Kell alleles, and perhaps acquiring these antibodies may be genetically driven. 32 , 33 In Omani population further studies will be needed to assess the effect of the number of transfusions on the immune response, the effect of the age at which the patient is first transfused, and the genetic makeup of recipients and donors on alloimmunization.…”

Section: Discussionmentioning

confidence: 99%

Alloimmunization in Patients With Sickle Cell Disease and Thalassaemia: Experience of Single Centre From Oman

Pathare

Alkindi²

2017

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

BackgroundBlood transfusion is an integral part of the supportive care for patients with sickle cell disease (SCD) and thalassaemia. The hazard of red cell alloimmunization, however, is one of the main complications of this therapy.ObjectivesThe aim of this study was to evaluate the prevalence of red cell alloimmunization in Omani patients with sickle cell anaemia and thalassemia.MethodsThis study included 262 patients whose historical transfusion records were available. One hundred and twenty-nine patients with thalassaemia who were attending the day care unit for regular transfusions, and 133 SCD patients admitted at our hospital were included in this study. The Diamed® gel system was used for the screening and identification of atypical antibodies.ResultsThe rate of alloimmunization in SCD patients was 31.6% (n=42, 95%CI, 24.87–40.66), whereas in patients with thalassaemia it was 20% (n=26; 95%CI, 13.9–27.6). Antibodies to E, e, C, c, D, K, S, Fyª, Kpª, Jkª and Cw were observed; 85% of the patients were also immunised with Rh and Kell antigens. Considering the two groups together, 8 developed nonspecific antibodies and 12 developed more than one antibody.ConclusionsRed cell transfusions were associated with a significant risk of alloimmunization. It is, therefore, imperative to perform an initial extended red cell phenotyping for both donors and recipients, and carefully select ABO, Rh and Kell matched donors. The higher incidence of alloimmunization in SCD patients is related to the inherent SCD-specific inflammatory state.

show abstract

Section: Discussionmentioning

confidence: 99%

Alloimmunization in Patients With Sickle Cell Disease and Thalassaemia: Experience of Single Centre From Oman

Pathare

Alkindi²

2017

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

show abstract

“…Recently, we reported a highly concordant KEL genotyping method between patients with hemoglobinopathies and blood donors in São Paulo City, Brazil. Our data suggested a high rate of racial admixture in African descent Brazilian patients with hemoglobinopathies, as well as in Brazilian blood donors, and possibly explain the lower risk for Kell alloimmunization detected in Brazilian patients when compared with North American and European studies 2 . Using the KEL*3,4 genotyping with the polymerase chain reaction (PCR)‐ Nla III‐restriction fragment length polymorphism (RFLP) technique described by Lee and coworkers, 3 in this study we detected (but not reported yet) 1.4% (3/208) blood donors with an abnormal digestion pattern (Fig.…”

mentioning

confidence: 53%

Novel IVS6‐13C>T mutation recognized as a cause of discrepancy between phenotyping and genotyping in KEL3,4* polymorphism identification

Boturão‐Neto¹,

Chiba²,

Bordin³

2010

Transfusion

View full text Add to dashboard Cite

tration. It can be proposed that a relapsing TTP known as rituximab-responsive should be retreated in emergency. The rapidity of the rituximab effect is supported by its ability to clear from the blood within a few hours a significant number of B cells, which is correlated to B-cell depletion within marrow and lymph nodes. 3 From undetectable ADAMTS13 at her third episode, a progressive increase was observed under rituximab. Despite the reported correlation between a persistent deficiency in ADAMTS13 and the risk of relapse, this is still a subject of controversy. 4 Thus, the absence of relapse under rituximab maintenance could be explained or not by this. Although plasma levels of rituximab are low or undetectable 4 months after its infusion, a 6-month frequency administration could be enough to achieve the long-term B-cell depletion necessary to maintain the remission. 5 Safety issues concerning a prolonged administration of rituximab should be outlined, but few data exist. 1 Early front-line therapy with rituximab for relapsing TTP patients previously responsive to the same drug could be a therapeutic option. For those who achieve remission, a rituximab maintenance schedule could also be considered, ideally within clinical trials, because our experience with this one patient is not enough to be raised as a solid recommendation.

show abstract

“…The five main Rhesus antigens (D, C, E, c, e) and K of the Kell system are the cause of most alloimmunizations after blood transfusion, especially in patients undergoing chronic transfusion therapy 1–3 . The prevention of hemolytic disease of the fetus and newborn caused by Rh and K antibodies is still a challenge in clinical practice due to the high immunogenicity of these antigens 4,5 . While the K phenotype arises due to a single base mutation, 698C > T (Exon 6), which replaces T193M, RhD differs by 32–35 amino acids from RhCE protein, and immunogenic RhD epitopes can be more easily recognized by specific T cell receptors, increasing the predisposition to anti‐D alloimmunization 6,7 …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] The prevention of hemolytic disease of the fetus and newborn caused by Rh and K antibodies is still a challenge in clinical practice due to the high immunogenicity of these antigens. 4,5 While the K phenotype arises due to a single base mutation, 698C > T (Exon 6), which replaces T193M, RhD differs by 32-35 amino acids from RhCE protein, and immunogenic RhD epitopes can be more easily recognized by specific T cell receptors, increasing the predisposition to anti-D alloimmunization. 6,7 The human leukocyte antigens (HLAs) play an important role in antigen presentation and have been investigated as potential susceptibility factors for red blood cell (RBC) alloimmunization as some patients are more susceptible to producing erythrocyte antibodies than others when stimulated.…”

Section: Introductionmentioning

confidence: 99%

HLA‐DRB1 molecules and the presentation of anchor peptides from RhD, RhCE, and KEL proteins

et al. 2021

View full text Add to dashboard Cite

Background Antigens from the Rh and Kell systems are recognized as the most immunogenic in clinical practice. This study evaluated the possible molecular mechanisms involved in the interaction of antigenic peptides with the DRB1 molecules, which help to explain the high frequency of anti‐K and association of D + C antibodies in transfusion and incompatible pregnancy. Study Design and Methods We included 201 patients with antibodies against antigens from the Rh and Kell systems and compare them with 174,015 controls. HLA‐DRB1 genotyping and in silico analysis were performed. The NetMHCIIpan software was used to identify RhD‐, RhCE‐, and KEL‐derived anchor peptides that bind to DRB1 molecules. Results HLA‐DRB1*15 is associated with an increased risk of D, C, E, and K alloimmunization, while the HLA‐DRB1*01 and *12 alleles are overrepresented in patients with anti‐C and anti‐D, respectively. In silico analysis showed that three polymorphic points (60I, 68S, and 103S) common to C and D antigens can be presented by several DRB1 molecules, including DRB1*15:01. The DRB1*09:01 molecule, although not showing statistical significance, was able to interact strongly with almost all five anchor peptides from the sequence containing the polymorphic determinants of E antigen, except 217‐WMFWPSVNS‐225. Conclusion The DRB1*15 molecule has specific physicochemical characteristics in residues 11P and 13R in the P4 pocket that can favor the response to various antigenic peptides. Anti‐K alloimmunization is unrestricted for interaction with specific DRB1 molecules, which suggests that almost all individuals in our population have DRB1 molecules capable of binding to KEL‐derived anchor peptides and produce anti‐K when stimulated.

show abstract

Molecular studies reveal a concordant KEL genotyping between patients with hemoglobinopathies and blood donors in Sao Paulo City, Brazil

Cited by 4 publications

References 1 publication

Alloimmunization in Patients With Sickle Cell Disease and Thalassaemia: Experience of Single Centre From Oman

Alloimmunization in Patients With Sickle Cell Disease and Thalassaemia: Experience of Single Centre From Oman

Novel IVS6‐13C>T mutation recognized as a cause of discrepancy between phenotyping and genotyping in KEL3,4* polymorphism identification

HLA‐DRB1 molecules and the presentation of anchor peptides from RhD, RhCE, and KEL proteins

Contact Info

Product

Resources

About

Molecular studies reveal a concordant KEL genotyping between patients with hemoglobinopathies and blood donors in Sao Paulo City, Brazil

Cited by 4 publications

References 1 publication

Alloimmunization in Patients With Sickle Cell Disease and Thalassaemia: Experience of Single Centre From Oman

Alloimmunization in Patients With Sickle Cell Disease and Thalassaemia: Experience of Single Centre From Oman

Novel IVS6‐13C>T mutation recognized as a cause of discrepancy between phenotyping and genotyping in KEL*3,4 polymorphism identification

HLA‐DRB1 molecules and the presentation of anchor peptides from RhD, RhCE, and KEL proteins

Contact Info

Product

Resources

About

Novel IVS6‐13C>T mutation recognized as a cause of discrepancy between phenotyping and genotyping in KEL3,4* polymorphism identification