Transgenic rats with high expression of HLA-B27 and human beta2-microglobulin (B27TR) develop a multisystem inflammatory disease resembling human inflammatory bowel disease (IBD) and spondyloarthritis (SpA). Tumour necrosis factor α (TNFα) has a crucial role in sustaining chronic inflammation in the gut and joints. The aim of this work was to evaluate whether TNFα blockade could prevent or reduce the inflammation of peripheral joints in B27TR. A first group of 9-week-old B27TR received anti-TNFα mAb or isotypic IgG2a,k up to the age of 18 weeks. An untreated group was monitored up to the age of 18 weeks and then randomly assigned to a 9-week treatment with anti-TNFα mAb or IgG2a,k. Each rat was monitored for clinical IBD and peripheral joint manifestations. After sacrifice the colon and hind paws were examined for macroscopical and microscopical pathological changes. Early TNFα blockade prevented, and late treatment improved IBD signs in B27TR. Erythema, edema, inflammatory infiltrate close to the tendons and enthesis, proliferating chondrocyte-like cells, signs of new endochondral bone ossification and bone erosion were observed in peripheral joints of 4/6 IgG2a,k-treated B27TR both at 18 and 27 weeks. Immunopositivity for phosphorylated Smad1/5/8 indicated that the process of joint remodelling was activated in B27TR. Some entheses showed chondroid nodules. Anti-TNFα treatment reduced inflammation and preserved the enthesis organization in most animals. Occasional and transient erythema and edema were still present in 3/6 of the late anti-TNFα-treated animals. Smad1/5/8 signalling was not inhibited by late anti-TNFα treatment. In B27TR, articular involvement follows IBD onset and develops at entheses. Early TNFα blockade prevents the onset of IBD and consequently the development of enthesitis in peripheral joints in the B27TR model of human SpA.

Evidence for the prevention of enthesitis in HLA-B27/hβ(2)m transgenic rats treated with a monoclonal antibody against TNF-α / A.F. Milia; L. Ibba-Manneschi; M. Manetti; G. Benelli; S. Generini; L. Messerini; M. Matucci-Cerinic. - In: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE. - ISSN 1582-1838. - STAMPA. - 15:(2011), pp. 270-279. [10.1111/j.1582-4934.2009.00984.x]

Evidence for the prevention of enthesitis in HLA-B27/hβ(2)m transgenic rats treated with a monoclonal antibody against TNF-α.

IBBA, LIDIA;MANETTI, MIRKO;BENELLI, GEMMA;GENERINI, SERGIO;MESSERINI, LUCA;MATUCCI CERINIC, MARCO
2011

Abstract

Transgenic rats with high expression of HLA-B27 and human beta2-microglobulin (B27TR) develop a multisystem inflammatory disease resembling human inflammatory bowel disease (IBD) and spondyloarthritis (SpA). Tumour necrosis factor α (TNFα) has a crucial role in sustaining chronic inflammation in the gut and joints. The aim of this work was to evaluate whether TNFα blockade could prevent or reduce the inflammation of peripheral joints in B27TR. A first group of 9-week-old B27TR received anti-TNFα mAb or isotypic IgG2a,k up to the age of 18 weeks. An untreated group was monitored up to the age of 18 weeks and then randomly assigned to a 9-week treatment with anti-TNFα mAb or IgG2a,k. Each rat was monitored for clinical IBD and peripheral joint manifestations. After sacrifice the colon and hind paws were examined for macroscopical and microscopical pathological changes. Early TNFα blockade prevented, and late treatment improved IBD signs in B27TR. Erythema, edema, inflammatory infiltrate close to the tendons and enthesis, proliferating chondrocyte-like cells, signs of new endochondral bone ossification and bone erosion were observed in peripheral joints of 4/6 IgG2a,k-treated B27TR both at 18 and 27 weeks. Immunopositivity for phosphorylated Smad1/5/8 indicated that the process of joint remodelling was activated in B27TR. Some entheses showed chondroid nodules. Anti-TNFα treatment reduced inflammation and preserved the enthesis organization in most animals. Occasional and transient erythema and edema were still present in 3/6 of the late anti-TNFα-treated animals. Smad1/5/8 signalling was not inhibited by late anti-TNFα treatment. In B27TR, articular involvement follows IBD onset and develops at entheses. Early TNFα blockade prevents the onset of IBD and consequently the development of enthesitis in peripheral joints in the B27TR model of human SpA.
15
270
279
Goal 3: Good health and well-being
A.F. Milia; L. Ibba-Manneschi; M. Manetti; G. Benelli; S. Generini; L. Messerini; M. Matucci-Cerinic
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/368689
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