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Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility / Evans, Dm; Spencer, Cc; Pointon, Jj; Su, Z; Harvey, D; Kochan, G; Oppermann, U; Dilthey, A; Pirinen, M; Stone, Ma; Appleton, L; Moutsianas, L; Leslie, S; Wordsworth, T; Kenna, Tj; Karaderi, T; Thomas, Gp; Ward, Mm; Weisman, Mh; Farrar, C; Bradbury, La; Danoy, P; Inman, Rd; Maksymowych, W; Gladman, D; Rahman, P; Spondyloarthritis Research Consortium of, Canada; Morgan, A; Marzo Ortega, H; Bowness, P; Gaffney, K; Gaston, Js; Smith, M; Bruges Armas, J; Couto, Ar; Sorrentino, Rosa; Paladini, Fabiana; Ferreira, Ma; Xu, H; Liu, Y; Jiang, L; Lopez Larrea, C; Díaz Peña, R; López Vázquez, A; Zayats, T; Band, G; Bellenguez, C; Blackburn, H; Blackwell, Jm; Bramon, E; Bumpstead, Sj; Casas, Jp; Corvin, A; Craddock, N; Deloukas, P; Dronov, S; Duncanson, A; Edkins, S; Freeman, C; Gillman, M; Gray, E; Gwilliam, R; Hammond, N; Hunt, Se; Jankowski, J; Jayakumar, A; Langford, C; Liddle, J; Markus, Hs; Mathew, Cg; Mccann, Ot; Mccarthy, Mi; Palmer, Cn; Peltonen, L; Plomin, R; Potter, Sc; Rautanen, A; Ravindrarajah, R; Ricketts, M; Samani, N; Sawcer, Sj; Strange, A; Trembath, Rc; Viswanathan, Ac; Waller, M; Weston, P; Whittaker, P; Widaa, S; Wood, Nw; Mcvean, G; Reveille, Jd; Wordsworth, Bp; Brown, Ma; Donnelly, P; Australo Anglo American Spondyloarthritis, Consortium; Wellcome Trust Case Control Consortium, 2. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 43:(2011), pp. 761-767. [10.1038/ng.873]

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.

SORRENTINO, Rosa;PALADINI, Fabiana;
2011

Abstract

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
2011
HLA-B27, ERAP1, ANKYLOSING SPONDYLITIS
01 Pubblicazione su rivista::01a Articolo in rivista
Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility / Evans, Dm; Spencer, Cc; Pointon, Jj; Su, Z; Harvey, D; Kochan, G; Oppermann, U; Dilthey, A; Pirinen, M; Stone, Ma; Appleton, L; Moutsianas, L; Leslie, S; Wordsworth, T; Kenna, Tj; Karaderi, T; Thomas, Gp; Ward, Mm; Weisman, Mh; Farrar, C; Bradbury, La; Danoy, P; Inman, Rd; Maksymowych, W; Gladman, D; Rahman, P; Spondyloarthritis Research Consortium of, Canada; Morgan, A; Marzo Ortega, H; Bowness, P; Gaffney, K; Gaston, Js; Smith, M; Bruges Armas, J; Couto, Ar; Sorrentino, Rosa; Paladini, Fabiana; Ferreira, Ma; Xu, H; Liu, Y; Jiang, L; Lopez Larrea, C; Díaz Peña, R; López Vázquez, A; Zayats, T; Band, G; Bellenguez, C; Blackburn, H; Blackwell, Jm; Bramon, E; Bumpstead, Sj; Casas, Jp; Corvin, A; Craddock, N; Deloukas, P; Dronov, S; Duncanson, A; Edkins, S; Freeman, C; Gillman, M; Gray, E; Gwilliam, R; Hammond, N; Hunt, Se; Jankowski, J; Jayakumar, A; Langford, C; Liddle, J; Markus, Hs; Mathew, Cg; Mccann, Ot; Mccarthy, Mi; Palmer, Cn; Peltonen, L; Plomin, R; Potter, Sc; Rautanen, A; Ravindrarajah, R; Ricketts, M; Samani, N; Sawcer, Sj; Strange, A; Trembath, Rc; Viswanathan, Ac; Waller, M; Weston, P; Whittaker, P; Widaa, S; Wood, Nw; Mcvean, G; Reveille, Jd; Wordsworth, Bp; Brown, Ma; Donnelly, P; Australo Anglo American Spondyloarthritis, Consortium; Wellcome Trust Case Control Consortium, 2. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 43:(2011), pp. 761-767. [10.1038/ng.873]
01a Articolo in rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/625165
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