OBJECTIVE: Arthritis is frequently seen in human lupus, but rarely in lupus models. Pristane-induced lupus (PIL) can be induced in various mouse strains such as BALB/c and C57BL/6. We herein characterize clinical and histological features of arthritis in the context of systemic lupus and provide a prudent comparison with models of rheumatoid arthritis (RA). METHODS: A total of 57 BALB/c mice received pristane (PIL group) and were analyzed for serum autoantibodies (anti-chromatin-, -histone, -Sm, -dsDNA), as well as for clinical features and histopathology of joints, lungs and kidneys. Joint pathology was quantified by image analysis and tissue cytometry. Ten C57BL/6 mice (Bl/6-PIL) and historical groups of two different RA models were analyzed accordingly. RESULTS: In BALB/c PIL, clinical arthritis started at three months, occurred finally in 79% of PIL (but not in controls, p<0.001) and correlated with areas of inflammation, erosion, cartilage damage, osteoclast numbers and total severity score (for all: r>0.7, p<0.001). After eight months, 58% of PIL (but no controls, p<0.001) had mild-erosive arthritis. In contrast to RA, the most frequent inflammatory cell type of the pannus was granulocytes (17.7%), PIL had lower numbers of osteoclasts, erosions rarely affected both layers of the cortical bone and there was no progression to complete joint destruction (even after one year of observation). Serum autoantibodies (auto-abs) preceded arthritis and became significantly elevated in all PIL; affected joints showed increased deposits of IgG (and IgM) within the inflammatory tissue, indicative of an ab-mediated process. PIL mice with arthritis also showed signs of pulmonary (100%) and renal (46%) lupus. In contrast to BALB/c, Bl/6-PIL mice did not develop any signs of arthritis. CONCLUSION: PIL in BALB/c mice is characterized by severe organ involvement, typical autoabs and by a mild-erosive arthritis with similarities to, but also with distinct differences from, RA. PIL may help to study arthritis along with other key features of systemic lupus erythematosus after therapeutic interventions or in knock-out models based on a BALB/c but not on a C57BL/6 background.
OBJECTIVE:Arthritis is frequently seen in human lupus, but rarely in lupus models. Pristane-induced lupus (PIL) can be induced in various mouse strains such as BALB/c and C57BL/6. We herein characterize clinical and histological features of arthritis in the context of systemic lupus and provide a prudent comparison with models of rheumatoid arthritis (RA). METHODS: A total of 57 BALB/c mice received pristane (PIL group) and were analyzed for serum autoantibodies (anti-chromatin-, -histone, -Sm, -dsDNA), as well as for clinical features and histopathology of joints, lungs and kidneys. Joint pathology was quantified by image analysis and tissue cytometry. Ten C57BL/6 mice (Bl/6-PIL) and historical groups of two different RA models were analyzed accordingly. RESULTS: In BALB/c PIL, clinical arthritis started at three months, occurred finally in 79% of PIL (but not in controls, p<0.001) and correlated with areas of inflammation, erosion, cartilage damage, osteoclast numbers and total severity score (for all: r>0.7, p<0.001). After eight months, 58% of PIL (but no controls, p<0.001) had mild-erosive arthritis. In contrast to RA, the most frequent inflammatory cell type of the pannus was granulocytes (17.7%), PIL had lower numbers of osteoclasts, erosions rarely affected both layers of the cortical bone and there was no progression to complete joint destruction (even after one year of observation). Serum autoantibodies (auto-abs) preceded arthritis and became significantly elevated in all PIL; affected joints showed increased deposits of IgG (and IgM) within the inflammatory tissue, indicative of an ab-mediated process. PIL mice with arthritis also showed signs of pulmonary (100%) and renal (46%) lupus. In contrast to BALB/c, Bl/6-PIL mice did not develop any signs of arthritis. CONCLUSION: PIL in BALB/c mice is characterized by severe organ involvement, typical autoabs and by a mild-erosive arthritis with similarities to, but also with distinct differences from, RA. PIL may help to study arthritis along with other key features of systemic lupus erythematosus after therapeutic interventions or in knock-out models based on a BALB/c but not on a C57BL/6 background.
Authors: Chiara Donadei; Andrea Angeletti; Chiara Cantarelli; Vivette D D'Agati; Gaetano La Manna; Enrico Fiaccadori; Julian K Horwitz; Huabao Xiong; Chiara Guglielmo; Susan Hartzell; Joren C Madsen; Umberto Maggiore; Peter S Heeger; Paolo Cravedi Journal: JCI Insight Date: 2019-04-23
Authors: F Facciotti; P Larghi; R Bosotti; C Vasco; N Gagliani; C Cordiglieri; S Mazzara; V Ranzani; E Rottoli; S Curti; A Penatti; B Karnani; Y Kobayashi; M Crosti; M Bombaci; J P van Hamburg; G Rossetti; R Gualtierotti; M Gerosa; S Gatti; S Torretta; L Pignataro; S W Tas; S Abrignani; M Pagani; F Grassi; P L Meroni; R A Flavell; J Geginat Journal: Proc Natl Acad Sci U S A Date: 2020-03-17 Impact factor: 11.205
Authors: Bernardo S Franklin; Lukas Bossaller; Dominic De Nardo; Jacqueline M Ratter; Andrea Stutz; Gudrun Engels; Christoph Brenker; Mark Nordhoff; Sandra R Mirandola; Ashraf Al-Amoudi; Matthew S Mangan; Sebastian Zimmer; Brian G Monks; Martin Fricke; Reinhold E Schmidt; Terje Espevik; Bernadette Jones; Andrew G Jarnicki; Philip M Hansbro; Patricia Busto; Ann Marshak-Rothstein; Simone Hornemann; Adriano Aguzzi; Wolfgang Kastenmüller; Eicke Latz Journal: Nat Immunol Date: 2014-06-22 Impact factor: 25.606
Authors: D Kienhöfer; J Hahn; I Schubert; C Reinwald; N Ipseiz; S C Lang; È Bosch Borràs; K Amann; C Sjöwall; A E Barron; A J Hueber; B Agerberth; G Schett; M H Hoffmann Journal: PLoS One Date: 2014-12-23 Impact factor: 3.240
Authors: WeiYu Lin; Dhaya Seshasayee; Wyne P Lee; Patrick Caplazi; Sami McVay; Eric Suto; Allen Nguyen; Zhonghua Lin; Yonglian Sun; Laura DeForge; Mercedesz Balazs; Flavius Martin; Ali A Zarrin Journal: Arthritis Rheumatol Date: 2015-01 Impact factor: 10.995