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

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.

Antibodies to human neutrophil antigen HNA-3b implicated in cases of neonatal alloimmune neutropenia.

BACKGROUND: Neonatal alloimmune neutropenia results from maternal alloimmunization to human neutrophil antigens. The alloantibodies involved in neonatal alloimmune neutropenia are against human neutrophil antigens HNA-1a, HNA-1b, HNA-1c, HNA-1d, HNA-2, HNA-3a, HNA-4a, HNA-4b, and HNA-5a; however, to date, antibodies specific to HNA-3b have not been reported. STUDY DESIGN AND METHODS: Blood samples from 10,000 unselected neonates were analyzed, resulting in the selection of 88 neutropenic newborns (neutrophil count <1.5 × 109 /L) from 83 mothers (three pairs of twins and one triplet). HNA-3 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism to identify the cases of maternal-fetal HNA-3 incompatibility. Serologic studies for detecting maternal HNA-3 alloantibodies were performed with the granulocyte agglutination test, the white blood cell immunofluorescence test, and a LABScreen Multi-HNA Kit. RESULTS: Genotyping studies identified 13 of 88 (14.8%) instances of maternal-fetal HNA-3 incompatibility, with all mothers typed as HNA-3a/a and neonates typed as HNA-3a/b. Serologic studies revealed that five of 13 (38.5%) mothers carried anti-HNA-3b plus human leukocyte antigen antibodies and that three of 13 (23.1%) mothers had anti-HNA-3b without human leukocyte antigen antibodies. CONCLUSION: Here, we report the first three cases of neonatal alloimmune neutropenia associated with HNA-3b antibodies resulting in a neonatal alloimmune neutropenia incidence of one in 3333 live births.

HNA-3 gene frequencies in Brazilians and a new polymerase chain reaction-restriction fragment length polymorphism method for HNA-3a/3b genotyping.

BACKGROUND: HNA-3 antigens are the result of a rs2288904 single-nucleotide polymorphism (SNP) in the CTL2, and the HNA-3a and HNA-3b variants are encoded by a guanine and adenine at Nucleotide Position 461. Anti-HNA-3 are involved in severe transfusion-related acute lung injury reactions and in neonatal alloimmune neutropenia. Since the distribution of the HNA-3 system was unknown in South Americans, in this study we determined the frequency of the HNA-3 alleles in Brazilians. STUDY DESIGN AND METHODS: DNA of 500 blood donors, 120 Xikrin Amerindians, 74 Japanese individuals, and 124 African Brazilians were genotyped for rs2288904 by a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay. The PCR product was digested with enzyme Taq(α) 1, specific to nucleotide guanine (HNA-3a). RESULTS: The results showed that the frequencies of the HNA-3a/HNA-3b alleles were 0.81/0.19 in blood donors, 1.00/0.00 in Amerindians, 0.63/0.37 in Japanese, and 0.85/0.15 in African Brazilians. All 81 individuals genotyped as HNA-3a/a did not present the SNP c.457T by molecular sequencing. CONCLUSION: The frequencies of HNA-3 genotypes in Brazilian blood donors is similar to that described in Caucasians; however, all Amerindians were HNA-3a/a, African Brazilians showed a lower frequency of HNA-3b/b, and Japanese had a higher prevalence of HNA-3b/b, suggesting that they may be at risk for developing anti-HNA-3a alloantibodies.

Transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related death in the United States and United Kingdom. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever and noncardiogeneic pulmonary edema, all occurring during or within 6 h after transfusion. Although the mechanism of TRALI has not been fully elucidated, it has been associated with human leukocyte antigen antibodies (class I, class II or neutrophil alloantigens) and with biologically active mediators in stored cellular blood components. Most of the donors implicated in cases of TRALI are multiparous women. Rarely diagnosed, TRALI can be confused with other causes of acute respiratory failure. Greater knowledge regarding TRALI on the part of clinicians could be crucial in preventing and treating this severe complication of blood transfusion.

Lesão pulmonar aguda associada à transfusão / Transfusion-related acute lung injury

Lesão pulmonar aguda associada à transfusão (transfusion-related acute lung injury, TRALI) é uma complicação clínica grave relacionada à transfusão de hemocomponentes que contêm plasma. Recentemente, TRALI foi considerada a principal causa de morte associada à transfusão nos Estados Unidos e Reino Unido. É manifestada tipicamente por dispnéia, hipoxemia, hipotensão, febre e edema pulmonar não cardiogênico, que ocorre durante ou dentro de 6 h, após completada a transfusão. Embora o exato mecanismo não tenha sido totalmente elucidado, postula-se que TRALI esteja associada à infusão de anticorpos contra antígenos leucocitários (classes I ou II ou aloantígenos específicos de neutrófilos) e a mediadores biologicamente ativos presentes em componentes celulares estocados. A maioria dos doadores implicados em casos da TRALI são mulheres multíparas. TRALI, além de ser pouco diagnosticada, pode ainda ser confundida com outras situações de insuficiência respiratória aguda. Um melhor conhecimento sobre TRALI pode ser crucial na prevenção e tratamento desta severa complicação transfusional.

Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related death in the United States and United Kingdom. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever and noncardiogeneic pulmonary edema, all occurring during or within 6 h after transfusion. Although the mechanism of TRALI has not been fully elucidated, it has been associated with human leukocyte antigen antibodies (class I, class II or neutrophil alloantigens) and with biologically active mediators in stored cellular blood components. Most of the donors implicated in cases of TRALI are multiparous women. Rarely diagnosed, TRALI can be confused with other causes of acute respiratory failure. Greater knowledge regarding TRALI on the part of clinicians could be crucial in preventing and treating this severe complication of blood transfusion.