Evidence for the prevention of enthesitis in HLA-B27/hβ(2)m transgenic rats treated with a monoclonal antibody against TNF-α.
Bottom Line: Early TNF-α blockade prevented, and late treatment improved IBD signs in B27TR.Anti-TNF-α treatment reduced inflammation and preserved the enthesis organization in most animals.Early TNF-α blockade prevents the onset of IBD and consequently the development of enthesitis in peripheral joints in the B27TR model of human SpA.
Affiliation: Department of Biomedicine, Division of Rheumatology, University of Florence, Florence, Italy. email@example.comShow MeSH
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Mentions: Immunohistochemistry was performed to identify cells expressing TNF-α in the affected joints of IgG2a,k-treated B27TR. In both 18- and 27-week-old rats, chondrocyte-like cells showed immunopositivity for TNF-α in the proliferating zone of the articular cartilage and at the fibrocartilaginous point of attachment of the entheses (Fig. 4A–C). Some vessels close to the entheses showed positive cells for TNF-α. In addition, immunostaining for nuclear phosphorylated Smad 1/5/8 (p-Smad1/5/8), a marker for active bone morphogenetic protein (BMP) signalling , was performed. Activation of Smad1/5/8 signalling was detected in spindle-shaped entheseal fibroblast-like cells, inflammatory cells and in round chondroblast-like cells (Fig. 5A, B). Moreover, proliferating and prehypertrophic chondrocyte-like cells showed strong p-Smad1/5/8-immunopositivity in the fibrocartilage at the point of entheseal attachment (Fig. 5C, D). Instead, hypertrophic chondrocytes were negative (Fig. 5D). Chondrocytes in the articular cartilage were also found positive for p-Smad1/5/8 (Fig. 5E, F). No difference in p-Smad1/5/8 expression was found between 18- and 27-week-old IgG2a,k-treated B27TR.
Affiliation: Department of Biomedicine, Division of Rheumatology, University of Florence, Florence, Italy. firstname.lastname@example.org