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.
DuboisELTuffanelliDL. Clinical manifestations of systemic lupus erythematosus. Computer analysis of 520 cases. JAMA1964; 190: 104–111.
2.
GrigorREdmondsJLewkoniaRBresnihanBHughesGR. Systemic lupus erythematosus. A prospective analysis. Ann Rheum Dis1978; 37: 121–128.
3.
StammTABauernfeindBCoenenM. Concepts important to persons with systemic lupus erythematosus and their coverage by standard measures of disease activity and health status. Arthritis Rheum2007; 57: 1287–1295.
4.
BauernfeindBAringerMProdingerB. Identification of relevant concepts of functioning in daily life in people with systemic lupus erythematosus: A patient Delphi exercise. Arthritis Rheum2009; 61: 21–28.
5.
van VugtRMDerksenRHKaterLBijlsmaJW. Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus. Ann Rheum Dis1998; 57: 540–544.
6.
BoutryNHachullaEFlipoRMCortetBCottenA. MR imaging findings in hands in early rheumatoid arthritis: comparison with those in systemic lupus erythematosus and primary Sjögren syndrome. Radiology2005; 236: 593–600.
7.
OstendorfBSchererASpeckerCMödderUSchneiderM. Jaccoud’s arthropathy in systemic lupus erythematosus: Differentiation of deforming and erosive patterns by magnetic resonance imaging. Arthritis Rheum2003; 48: 157–165.
8.
Armas-CruzRHarneckerJDucachGJalilJGonzalezF. Clinical diagnosis of systemic lupus erythematosus. Am J Med1958; 25: 409–419.
9.
CruickshankB. Lesions of joint and tendon sheaths in systemic lupus erythematosus. Ann Rheum Dis1959; 18: 111–119.
10.
GoldenbergDLCohenAS. Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease. Medicine (Baltimore)1978; 57: 239–252.
11.
LabowitzRSchumacherHRJr. Articular manifestations of systemic lupus erythematosus. Ann Intern Med1971; 74: 911–921.
12.
NatourJMontezzoLCMouraLAAtraE. A study of synovial membrane of patients with systemic lupus erythematosus (SLE). Clin Exp Rheumatol1991; 9: 221–225.
13.
WallaceDThe musculoskeletal system. In: WallaceD (ed.) Dubois' Lupus Erythematosus, 5th ed. Baltimore, MD: Williams & Wilkins, 1997, pp. 635–651.
14.
ItoMRTerasakiSItohJKatohHYoneharaSNoseM. Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand. Arthritis Rheum1997; 40: 1054–1063.
15.
ReevesWHLeePYWeinsteinJSSatohMLuL. Induction of autoimmunity by pristane and other naturally occurring hydrocarbons. Trends Immunol2009; 30: 455–464.
16.
FurukawaFTanakaHSekitaKNakamuraTHoriguchiYHamashimaY. Dermatopathological studies on skin lesions of MRL mice. Arch Dermatol Res1984; 276: 186–194.
17.
FurukawaFYoshimasuT. Animal models of spontaneous and drug-induced cutaneous lupus erythematosus. Autoimmun Rev2005; 4: 345–350.
18.
HangLTheofilopoulosANDixonFJ. A spontaneous rheumatoid arthritis-like disease in MRL/l mice. J Exp Med1982; 155: 1690–1701.
19.
KoopmanWJGayS. The MRL-lpr/lpr mouse. A model for the study of rheumatoid arthritis. Scand J Rheumatol Suppl1988; 75: 284–289.
20.
DahlgrenJTakharHAnderson-MahoneyPKotlermanJTarrJWarshawR. Cluster of systemic lupus erythematosus (SLE) associated with an oil field waste site: A cross sectional study. Environ Health2007; 6: 8–8.
21.
MayesMD. Epidemiologic studies of environmental agents and systemic autoimmune diseases. Environ Health Perspect1999; 107(Suppl 5): 743–748.
22.
SatohMKurodaYYoshidaH. Induction of lupus autoantibodies by adjuvants. J Autoimmun2003; 21: 1–9.
23.
KurodaYNacionalesDCAkaogiJReevesWHSatohM. Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine. Biomed Pharmacother2004; 58: 325–337.
24.
WooleyPHSudSWhalenJDNasserS. Pristane-induced arthritis in mice. V. Susceptibility to pristane-induced arthritis is determined by the genetic regulation of the T cell repertoire. Arthritis Rheum1998; 41: 2022–2031.
25.
ChapdelaineJMWhalenJDWooleyPH. Pristane induced arthritis. II. Genetic regulation in F1 hybrid mice and cellular immune abnormalities following pristane injection. Autoimmunity1991; 8: 215–220.
26.
WooleyPHSeiboldJRWhalenJDChapdelaineJM. Pristane-induced arthritis. The immunologic and genetic features of an experimental murine model of autoimmune disease. Arthritis Rheum1989; 32: 1022–1030.
27.
PotterMWaxJS. Genetics of susceptibility to pristane-induced plasmacytomas in BALB/cAn: Reduced susceptibility in BALB/cJ with a brief description of pristane-induced arthritis. J Immunol1981; 127: 1591–1595.
28.
PattenCBushKRiojaI. Characterization of pristane-induced arthritis, a murine model of chronic disease: Response to antirheumatic agents, expression of joint cytokines, and immunopathology. Arthritis Rheum2004; 50: 3334–3345.
29.
HopkinsSJFreemontAJJaysonMI. Pristane-induced arthritis in Balb/c mice. I. Clinical and histological features of the arthropathy. Rheumatol Int1984; 5: 21–28.
30.
BedwellAEElsonCJHintonCE. Immunological involvement in the pathogenesis of pristane-induced arthritis. Scand J Immunol1987; 25: 393–398.
31.
HayerSRedlichKKorbAHermannSSmolenJSchettG. Tenosynovitis and osteoclast formation as the initial preclinical changes in a murine model of inflammatory arthritis. Arthritis Rheum2007; 56: 79–88.
32.
BlümlSBinderNBNiederreiterB. Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model of erosive arthritis. Arthritis Rheum2010; 62: 1608–1619.
33.
ZwerinaKKoendersMHueberA. Anti IL-17A therapy inhibits bone loss in TNF-alpha-mediated murine arthritis by modulation of the T-cell balance. Eur J Immunol2012; 42: 413–423.
34.
RedlichKHayerSRicciR. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest2002; 110: 1419–1427.
35.
PaisansinsupTDeshmukhUSChowdharyVRLuthraHSFuSMDavidCS. HLA class II influences the immune response and antibody diversification to Ro60/Sjögren’s syndrome-A: Heightened antibody responses and epitope spreading in mice expressing HLA-DR molecules. J Immunol2002; 168: 5876–5884.
36.
DumortierHMonneauxFJahn-SchmidB. B and T cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice. J Immunol2000; 165: 2297–2305.
MelegariABonaguriCRussoALuisitaBTrentiTLippiG. A comparative study on the reliability of an automated system for the evaluation of cell-based indirect immunofluorescence. Autoimmun Rev2012; 11: 713–716.
39.
HayerSRedlichKKorbAHermannSSmolenJSchettG. Tenosynovitis and osteoclast formation as the initial preclinical changes in a murine model of inflammatory arthritis. Arthritis Rheum2007; 56: 79–88.
40.
SchettGTuerkB. Bone histomorphometry in arthritis models. Methods Mol Med2007; 135: 269–283.
41.
ParfittAMDreznerMKGlorieuxFH. Bone histomorphometry: Standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res1987; 2: 595–610.
42.
RedlichKGörtzBHayerS. Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis. Am J Pathol2004; 164: 543–555.
43.
EferlRHasselblattPRathM. Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1. Proc Natl Acad Sci USA2008; 105: 10525–10530.
44.
LeonardJPLacasceASSmithMR. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood2012; 119: 4597–4607.
45.
BlümlSBonelliMNiederreiterB. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum2011; 63: 1281–1288.
46.
RichardsHBSatohMShawMLibertCPoliVReevesWH. Interleukin 6 dependence of anti-DNA antibody production: Evidence for two pathways of autoantibody formation in pristane-induced lupus. J Exp Med1998; 188: 985–990.
47.
SavareseESteinbergCPawarRD. Requirement of Toll-like receptor 7 for pristane-induced production of autoantibodies and development of murine lupus nephritis. Arthritis Rheum2008; 58: 1107–1115.
48.
HopkinsSJFreemontAJJaysonMI. Pristane-induced arthritis in BALB/c mice. Curr Top Microbiol Immunol1985; 122: 213–220.
49.
Jiménez-BojERedlichKTurkB. Interaction between synovial inflammatory tissue and bone marrow in rheumatoid arthritis. J Immunol2005; 175: 2579–2588.
50.
HayerSPolzerKBrandlA. B-cell infiltrates induce endosteal bone formation in inflammatory arthritis. J Bone Miner Res2008; 23: 1650–1660.
51.
ChowdharyVRGrandeJPLuthraHSDavidCS. Characterization of haemorrhagic pulmonary capillaritis: Another manifestation of pristane-induced lupus. Rheumatology (Oxford)2007; 46: 1405–1410.
52.
BarkerTTLeePYKelly-ScumpiaKM. Pathogenic role of B cells in the development of diffuse alveolar hemorrhage induced by pristane. Lab Invest2011; 91: 1540–1550.
53.
HahnBAnimal models of systemic lupus erythematosus. In: WallaceD (ed.) Dubois’ Lupus Erthematosus, 5th ed. Baltimore, MD: Williams & Wilkins, 1997.
54.
HolmdahlRMoJNordlingC. Collagen induced arthritis: An experimental model for rheumatoid arthritis with involvement of both DTH and immune complex mediated mechanisms. Clin Exp Rheumatol1989; 7 Suppl 3: S51–S55.
55.
HolmdahlRAnderssonMEGoldschmidtTJ. Collagen induced arthritis as an experimental model for rheumatoid arthritis. Immunogenetics, pathogenesis and autoimmunity. APMIS1989; 97: 575–584.
56.
BoumpasDTEleftheriadesEGTsokosGC. Cellular immunity in systemic lupus erythematosus. In Vivo1988; 2: 41–45.
57.
HamiltonKJSatohMSwartzJRichardsHBReevesWH. Influence of microbial stimulation on hypergammaglobulinemia and autoantibody production in pristane-induced lupus. Clin Immunol Immunopathol1998; 86: 271–279.
58.
SatohMKumarAKanwarYSReevesWH. Anti-nuclear antibody production and immune-complex glomerulonephritis in BALB/c mice treated with pristane. Proc Natl Acad Sci USA1995; 92: 10934–10938.
59.
CalvaniNSatohMCrokerBPReevesWHRichardsHB. Nephritogenic autoantibodies but absence of nephritis in Il-12p35-deficient mice with pristane-induced lupus. Kidney Int2003; 64: 897–905.
60.
LevittNGFernandez-MadridFWooleyPH. Pristane induced arthritis in mice. IV. Immunotherapy with monoclonal antibodies directed against lymphocyte subsets. J Rheumatol1992; 19: 1342–1347.
61.
RichardsHBSatohMShawMLibertCPoliVReevesWH. Interleukin 6 dependence of anti-DNA antibody production: Evidence for two pathways of autoantibody formation in pristane-induced lupus. J Exp Med1998; 188: 985–990.
62.
RichardsHBSatohMJennetteJCCrokerBPYoshidaHReevesWH. Interferon-gamma is required for lupus nephritis in mice treated with the hydrocarbon oil pristane. Kidney Int2001; 60: 2173–2180.
63.
ArbuckleMRMcClainMTRubertoneMV. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med2003; 349: 1526–1533.
64.
FeinglassEJArnettFCDorschCAZizicTMStevensMB. Neuropsychiatric manifestations of systemic lupus erythematosus: Diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore)1976; 55: 323–339.
65.
HayaharaCIkedaKSakanishiYOtaT. Incidence of serum rheumatoid factors in elder non-rheumatic individuals [in Japanese]. Rinsho Byori Jpn J Clin Pathol2010; 58: 211–215.
66.
MarizHASatoEIBarbosaSHRodriguesSHDellavanceAAndradeLE. Pattern on the antinuclear antibody-HEp-2 test is a critical parameter for discriminating antinuclear antibody-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum2011; 63: 191–200.
