Assuntos
Anemia Hemolítica Autoimune/induzido quimicamente , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Talidomida/análogos & derivados , Anemia Hemolítica Autoimune/tratamento farmacológico , Antineoplásicos/efeitos adversos , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Lenalidomida , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Besides ABO and RH, the KEL blood group system, including the two antithetical antigens KEL1 and KEL2, is the most important owing to the frequent appearance of anti-KEL alloantibodies and their considerable clinical significance. So far, only limited information was available on KEL variant alleles determining the rare silent KELnull and KELel phenotypes with absent or diminished KEL antigen expression detected only by adsorption-elution techniques, respectively. STUDY DESIGN AND METHODS: For a systematic investigation of the KELnull and KELel phenotypes, 401 KEL:1,-2 samples (representing 2.6% of all Austrian KEL:1,-2 samples) and 811 KEL:1,2 samples were genotyped for the KEL*1/KEL*2-specific single-nucleotide polymorphism. All heterozygous KEL*1/KEL*2 and 4 additional KELnull samples were subjected to detailed immunohematologic examination and allele-specific sequencing. RESULTS: In 14 KEL:1,-2 samples, discrepant KEL*1/KEL*2 heterozygosity was observed, indicating the presence of silent or barely expressed KEL*2 alleles, whereas all KEL:1,2 individuals were homozygous for KEL*2. In the course of further molecular analysis, 8 novel KEL*2null and 2 KEL*2el alleles were discovered, representing 67 and 33 percent of previously known KEL*2null- and KEL*2el-encoding alleles, respectively. In addition, two different known KEL*2null and KEL*2el alleles each were confirmed. The immunohematologic properties of KEL variant red blood cells were defined by extended KEL phenotyping and flow cytometric KEL1, KEL2, KEL4, and KEL7 antigen as well as total Kell protein quantification. CONCLUSION: For the first time, exact KELnull and KELel population frequencies could be established in this population.
Assuntos
Alelos , Variação Genética , Sistema do Grupo Sanguíneo de Kell/genética , Sequência de Aminoácidos , Áustria , Sequência de Bases , Doadores de Sangue , Análise Mutacional de DNA , Eritrócitos/imunologia , Eritrócitos/metabolismo , Citometria de Fluxo , Frequência do Gene , Heterogeneidade Genética , Genótipo , Geografia , Humanos , Sistema do Grupo Sanguíneo de Kell/imunologia , Dados de Sequência Molecular , Fenótipo , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
BACKGROUND: RHD blood group alleles with reduced or absent antigen expression are a clinically significant and heterogeneous group. STUDY DESIGN AND METHODS: To detail population genetics data on apparently D- individuals in central Europe, a six-center study was performed with participants from Austria, Germany, Slovenia, Switzerland, and Russia. A total of 1700 serologically D- samples, positive for C and/or E, were investigated. RESULTS: Observed unexpressed RHD alleles were 59 RHD-CE-D+ hybrid alleles, 9 apparently regular RHD, 1 new RHD(Y401X); DELs were 8 RHD(M295I), 6 RHD(IVS3+1G>A), and 1 new RHD(X418L); and weakly expressed RHDs were 2 weak D type 5, 1 weak D type 1, 1 RHD category VI type 1, and 1 novel weak D type 26. Although weak D type 26 was shown to have one of the lowest D antigen densities ever observed, it gave rise to anti-D immunization in a transfused D- individual. CONCLUSION: The relative occurrence of RHD among serologically D- samples, positive for C and/or E, differed significantly in the investigated central European regions. Considering the growing use of molecular typing techniques, correct identification of blood group alleles with scarce or missing antigen expression is of utmost clinical importance and requires reliable population-based frequency data.
