Rheumatoid Arthritis (RA) is characterized by the formation of the synovial pannus, laden with inflammatory cells, which is hyperplastic and aggressive. Proliferation of new blood vessels is a prominent feature of the rheumatoid pannus. We have shown that a heterogeneity of function exists among macrophages isolated and purified directly from human rheumatoid synovial tissue in terms of their angiogenic activity. Only one subpopulation of macrophages possessed the ability to induce new blood vessel growth while other subpopulations did not. We propose to determine whether this functional macrophage heterogeneity extends to other activities of rheumatoid monocyte/macrophages, such as: production of Macrophage- derived growth factor (MDGF), Lysozyme, and Mononuclear cell factor (MCF). Since, despite the functional heterogeneity of these macrophages, no commercially available monoclonal antibody distinguishes these unique macrophage subpopulations, we plan to attempt to produce monoclonal antibodies directed against rheumatoid synovial macrophage subpopulations. Balb/c mice will be inoculated with macrophages from the RA synovial subpopulations. Spleen cells will be fused with HS-1 myeloma cells and hybridoma selection and cloning will be performed. Clones producing antibodies that react specifically with individual subpopulations will be sought. To determine whether angiogenic macrophages exists only with milieu of the joint, we will examine peripheral blood monocytes, the precursors of macrophages from patients with RA. Finally, we intend to study whether the angiogenic activity of macrophages can be modulated by antirheumatic drugs including penicillamine, gold sodium thiomalate, auranofin, and dexamethasone. Together, these observations should yield valuable insights into the pathogenesis of RA and into the mechanism of action of the drugs used to combat this potentially crippling disease.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Poornima, I G; Shields, K; Kuller, L H et al. (2018) Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls. Lupus :961203317751060
Demirci, F Yesim; Wang, Xingbin; Morris, David L et al. (2017) Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus. J Med Genet 54:381-389
Demirci, F Yesim; Wang, Xingbin; Kelly, Jennifer A et al. (2016) Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry. Arthritis Rheumatol 68:174-83
Zhao, Jian; Giles, Brendan M; Taylor, Rhonda L et al. (2016) Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA. Ann Rheum Dis 75:242-52
Kottyan, Leah C; Zoller, Erin E; Bene, Jessica et al. (2015) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. Hum Mol Genet 24:582-96
Parker, Ben; Urowitz, Murray B; Gladman, Dafna D et al. (2015) Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort. Ann Rheum Dis 74:1530-6
Martins, M; Williams, A H; Comeau, M et al. (2015) Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study. Genes Immun 16:142-50
Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence et al. (2014) Lymphoma risk in systemic lupus: effects of disease activity versus treatment. Ann Rheum Dis 73:138-42
Lertratanakul, Apinya; Wu, Peggy; Dyer, Alan R et al. (2014) Risk factors in the progression of subclinical atherosclerosis in women with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 66:1177-85
Kaiser, Rachel; Tang, Ling Fung; Taylor, Kimberly E et al. (2014) A polymorphism in TLR2 is associated with arterial thrombosis in a multiethnic population of patients with systemic lupus erythematosus. Arthritis Rheumatol 66:1882-7

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