RESUMO
BACKGROUND: All antigens described in the KN blood group system are located in the long homologous repeat D (LHR-D) of complement receptor 1 (CR1). While there have been reports that some sera react only with the long homologous repeat C (LHR-C), the antigens in LHR-C are unknown. STUDY DESIGN AND METHODS: Recombinant LHR-C and LHR-D were used to identify antibodies directed against LHR-C of CR1, into which a point mutation was introduced to characterize the underlying blood group antigens. In addition, database studies to define haplotypes of CR1 were performed. RESULTS: Several antisera were identified that were specific against CR1 p.1208His and against CR1 p.1208Arg, located in LHR-C. Fifteen KN haplotypes were found in the Ensembl genome browser. It was shown that due to a linkage disequilibrium anti-CR1 p.1208His may be mistaken for anti-KCAM. CONCLUSION: A novel antithetical KN blood group antigen pair was found at position p.1208 of CR1, for which the names DACY and YCAD are proposed. Antibodies against these two novel antigens seem to contribute to more than a quarter of all KN sera in Europe.
Assuntos
Antígenos de Grupos Sanguíneos , Mutação Puntual , Polimorfismo Genético , Receptores de Complemento 3b , Substituição de Aminoácidos , Anticorpos/química , Anticorpos/imunologia , Antígenos de Grupos Sanguíneos/química , Antígenos de Grupos Sanguíneos/genética , Antígenos de Grupos Sanguíneos/imunologia , Europa (Continente) , Humanos , Domínios Proteicos , Receptores de Complemento 3b/química , Receptores de Complemento 3b/genética , Receptores de Complemento 3b/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologiaRESUMO
This study examined the antibacterial properties of nineteen benzoxazole, isoniazid, ethionamide and salicylanilide derivatives against Staphylococcus aureus (S. aureus). It was found that three salicylanilide-derived compounds demonstrated antistaphylococcal activity: 5-Chloro-2-hydroxy-N-(4-(trifluoromethyl)phenyl)benzamide (5-Cl-4'-CF3- SAL), 4-chloro-2-(3-chlorophenylcarbamyoyl)phenyl)-2-(benzyloxycarbonylamino)propanoate (AIM31) and 4-chloro-2- (4-(trifluoromethyl)phenylcarbamoyl)phenyl acetate (AIM33). Investigation of the chemical structures of these three compounds and comparison with a non-inhibitory salicylanilide compound (i.e. 5,3'-diCl-SAL) illustrated that different combinations of chemical groups at defined positions on the salicylanilide core structure had a marked influence on antistaphylococcal activity. The most effective compound was AIM33 which inhibited staphylococcal growth and displayed an initial MIC value of 3.12 µg ml(-1) and subsequent investigation revealed that an MIC as low as of 0.5 µg ml(-1) was achievable. In this case, the dual presence of a trifluoromethyl group and an acetylated phenolic hydroxyl to the salicylanilide core structure led to greatly enhanced activity.
