Identification of HLA-DRPheβ47 as the susceptibility marker of hypersensitivity to beryllium in individuals lacking the berylliosis-associated supratypic marker HLA-DPGluβ69Reportar como inadecuado




Identification of HLA-DRPheβ47 as the susceptibility marker of hypersensitivity to beryllium in individuals lacking the berylliosis-associated supratypic marker HLA-DPGluβ69 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Respiratory Research

, 6:94

First Online: 14 August 2005Received: 31 March 2005Accepted: 14 August 2005

Abstract

BackgroundSusceptibility to beryllium Be-hypersensitivity BH has been associated with HLA-DP alleles carrying a glutamate at position 69 of the HLA-DP β-chain HLA-DPGlu69 and with several HLA-DP -DQ and -DR alleles and polymorphisms. However, no genetic associations have been found between BH affected subjects not carrying the HLA-DPGlu69 susceptibility marker.

MethodsIn this report, we re-evaluated an already described patient populations after 7 years of follow-up including new 29 identified BH subjects. An overall population 36 berylliosis patients and 38 Be-sensitization without lung granulomas and 86 Be-exposed controls was analysed to assess the role of the individual HLA-class II polymorphisms associated with BH-susceptibility in HLA-DPGlu69 negative subjects by univariate and multivariate analysis.

ResultsAs previously observed in this population the HLA-DPGlu69 markers was present in higher frequency in berylliosis patients 31 out of 36, 86% than in Be-sensitized 21 out of 38, 55%, p = 0.008 vs berylliosis and 41 out of 86 48%, p < 0.0001 vs berylliosis, p = 0.55 vs Be-sensitized Be-exposed controls.

However, 22 subjects presenting BH did not carry the HLA-DPGlu69 marker. We thus evaluated the contribution of all the HLA-DR -DP and -DQ polymorphisms in determining BH susceptibility in this subgroup of HLA-Glu69 subjects. In HLA-DPGlu69-negatives a significant association with BH was found for the HLA-DQLeu26, for the HLA-DRB1 locus residues Ser13, Tyr26, His32, Asn37, Phe47 and Arg74 and for the HLA-DRB3 locus clusterized residues Arg11, Tyr26, Asp28, Leu38, Ser60 and Arg74. HLA-DRPhe47 OR 2.956, p < 0.05 resulting independently associated with BH. Further, Be-stimulated T-cell proliferation in the HLA-DPGlu69-negative subjects all carrying HLA-DRPhe47 was inhibited by the anti-HLA-DR antibody range 70–92% inhibition significantly more than by the anti-HLA-DP antibody range: 6–29%; p < 0.02 compared to anti-HLA-DR while it was not affected by the anti-HLA-DQ antibody.

ConclusionWe conclude that HLA-DPGlu69 is the primary marker of Be-hypersensitivity and HLA-DRPhe47 is associated with BH in Glu69-negative subjects, likely playing a role in Be-presentation and sensitization.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-6-94 contains supplementary material, which is available to authorized users.

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Autor: Massimo Amicosante - Floriana Berretta - Milton Rossman - Richard H Butler - Paola Rogliani - Ella van den Berg-Loonen - Ce

Fuente: https://link.springer.com/







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