- SSc is a disease of unknown origin with the highest incidence occurring in females predominantly after child-bearing years. Recent research has revealed that fetal cells can survive in the maternal circulation for many years. Graft-versus-Host Disease (GVDH) has many similar clinical features to SSc although no evidence for GVHD in SSc has been identified. This investigator has identified by PCR and fluorescence in-situ hybridization (FISH) the presence of Y chromosome nucleated cells in 58% of skin biopsies from active lesions in patients with SSc and 46% of peripheral blood tested of female SSc patients. The investigato hypothesizes that these cells have become activated and have established a GVHD-like response in some female SSc patients. The investigator proposes in the current studies to identify and characterize the fetal cells in frozen and paraffin-embedded section of affected lung, skin, and kidneys in patient with early disease by a combination of magnetic cell sorting, immunophenotyping, and FISH. In addition, she proposes to examine the pattern of cytokine expression of the fetal cells in histologic sections and to isolate, clone, and expand Y chromosome nucleated cells from active lesions. She will also investigate whether expanded lymphocytes from the active lesion can induce Type I collagen mRNA in normal fibroblasts. The studies proposed in this application will identify and functionally characterize the Y chromosome positive cells found in the active lesion of SSc women. Obviously, the aims of this proposal cannot address the pathogenesis of SSc occurring in males, or in woman who have not had recognized pregnancies or male offspring.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AR045399-05
Application #
6511927
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Gretz, Elizabeth
Project Start
1998-08-15
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$113,400
Indirect Cost
Name
Thomas Jefferson University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Sawaya, H H B; Jimenez, S A; Artlett, C M (2004) Quantification of fetal microchimeric cells in clinically affected and unaffected skin of patients with systemic sclerosis. Rheumatology (Oxford) 43:965-8
Cox, Lori A; Ramos, Ronald C; Dennis, Tara N et al. (2003) Detection of microchimeric cells in the peripheral blood of nonpregnant women is enhanced by magnetic cell sorting before PCR. Clin Chem 49:309-12
Artlett, Carol M (2003) Microchimerism and scleroderma: an update. Curr Rheumatol Rep 5:154-9
Artlett, Carol M; Cox, Lori A; Ramos, Ronald C et al. (2002) Increased microchimeric CD4+ T lymphocytes in peripheral blood from women with systemic sclerosis. Clin Immunol 103:303-8
Artlett, C M; Rasheed, M; Russo-Stieglitz, K E et al. (2002) Influence of prior pregnancies on disease course and cause of death in systemic sclerosis. Ann Rheum Dis 61:346-50
Artlett, C M; Ramos, R; Jiminez, S A et al. (2000) Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group. Lancet 356:2155-6
Artlett, C M; Cox, L A; Jimenez, S A (2000) Detection of cellular microchimerism of male or female origin in systemic sclerosis patients by polymerase chain reaction analysis of HLA-Cw antigens. Arthritis Rheum 43:1062-7
Christner, P J; Artlett, C M; Conway, R F et al. (2000) Increased numbers of microchimeric cells of fetal origin are associated with dermal fibrosis in mice following injection of vinyl chloride. Arthritis Rheum 43:2598-605