Sarcoidosis is a systemic granulomatosis disease of unknown origin where a number of microbes, in particular M tuberculosis and non-tuberculous mycobacteria, have been hypothesized to play a role in disease pathogenesis, possibly through bacterial antigen-driven hypersensitivity. To test this concept, we used bioinformatic tools allowing the identification of antigenic peptides in whole microbial genomes to analyze the interaction between the expressed HLA-DR gene allelic variants and the HLA-DR immunome of all pathogenic bacteria in a population of 149 sarcoidosis affected subjects and 447 controls, all HLA-typed at high resolution. We show here that patients with the Lofgren's syndrome, express HLA-DR alleles that recognize in silico a significantly higher number of bacterial antigen epitopes compared to the control population (18,496+9,114 vs 17,954+8,742; p<0.00001), and the chronic sarcoidosis affected population (17,954+8,742; p<0.00001 vs Lofgren's and controls). Further, the analysis of the ability of the HLA-DR allele combinations expressed by the Lofgren and the chronic sarcoidosis affected subjects to recognize M avium epitopes demonstrates that a significantly larger number of Lofgren's are capable of top affinity recognition, compared to chronic sarcoidosis (45% vs 17%, p<0.0037). Finally, both Lofgren's and chronic sarcoidosis subjects expressed HLA-DR allele combinations capable of M tuberculosis and M avium epitope recognition at higher affinity than tuberculosis affected subjects (p<0.01 all comparisons). In conclusion, we propose that - at least in a subgroup of affected subjects sarcoidosis might be part of a spectrum of granulomatous responses to several agents where the Lofgren's syndrome represents the hyper-reactive end of the spectrum while pulmonary tuberculosis and atypical mycobacterial infections might represent the opposite end. (Sarcoidosis Vasc Diffuse Lung Dis 2008; 25: 100-116)

Saltini, C., Pallante, M., Puxeddu, E., Contini, S., Voorter, C.e., Drent, M., et al. (2008). M. avium binding to HLA-DR expressed alleles in silico: A model of phenotypic susceptibility to sarcoidosis. SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES, 25(2), 100-116.

M. avium binding to HLA-DR expressed alleles in silico: A model of phenotypic susceptibility to sarcoidosis

SALTINI, CESARE;PALLANTE, MARCO;PUXEDDU, ERMANNO;AMICOSANTE, MASSIMO
2008-01-01

Abstract

Sarcoidosis is a systemic granulomatosis disease of unknown origin where a number of microbes, in particular M tuberculosis and non-tuberculous mycobacteria, have been hypothesized to play a role in disease pathogenesis, possibly through bacterial antigen-driven hypersensitivity. To test this concept, we used bioinformatic tools allowing the identification of antigenic peptides in whole microbial genomes to analyze the interaction between the expressed HLA-DR gene allelic variants and the HLA-DR immunome of all pathogenic bacteria in a population of 149 sarcoidosis affected subjects and 447 controls, all HLA-typed at high resolution. We show here that patients with the Lofgren's syndrome, express HLA-DR alleles that recognize in silico a significantly higher number of bacterial antigen epitopes compared to the control population (18,496+9,114 vs 17,954+8,742; p<0.00001), and the chronic sarcoidosis affected population (17,954+8,742; p<0.00001 vs Lofgren's and controls). Further, the analysis of the ability of the HLA-DR allele combinations expressed by the Lofgren and the chronic sarcoidosis affected subjects to recognize M avium epitopes demonstrates that a significantly larger number of Lofgren's are capable of top affinity recognition, compared to chronic sarcoidosis (45% vs 17%, p<0.0037). Finally, both Lofgren's and chronic sarcoidosis subjects expressed HLA-DR allele combinations capable of M tuberculosis and M avium epitope recognition at higher affinity than tuberculosis affected subjects (p<0.01 all comparisons). In conclusion, we propose that - at least in a subgroup of affected subjects sarcoidosis might be part of a spectrum of granulomatous responses to several agents where the Lofgren's syndrome represents the hyper-reactive end of the spectrum while pulmonary tuberculosis and atypical mycobacterial infections might represent the opposite end. (Sarcoidosis Vasc Diffuse Lung Dis 2008; 25: 100-116)
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/10 - Malattie dell'Apparato Respiratorio
English
Con Impact Factor ISI
Chronic sarcoidosis; Epitope prediction; HLA-DR; Löfgren's syndrome; Susceptibility; T-cell response; Tuberculosis
epitope; HLA DR antigen; allele; antigen binding; article; atypical mycobacteriosis; bacterial genome; bioinformatics; chronic disease; computer model; controlled study; gene expression; genetic susceptibility; granulomatous inflammation; human; lofgren syndrome; lung tuberculosis; major clinical study; Mycobacterium avium; Mycobacterium tuberculosis; nonhuman; pathogenesis; phenotype; priority journal; sarcoidosis
Saltini, C., Pallante, M., Puxeddu, E., Contini, S., Voorter, C.e., Drent, M., et al. (2008). M. avium binding to HLA-DR expressed alleles in silico: A model of phenotypic susceptibility to sarcoidosis. SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES, 25(2), 100-116.
Saltini, C; Pallante, M; Puxeddu, E; Contini, S; Voorter, Ce; Drent, M; Amicosante, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/56922
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