Abstract

This proposal will test the hypothesis that the occurrence of hypocomplementemia, proteinuria, thrombocytopenia, and lupus anticoagulant during the course of pregnancy in patients with systemic lupus erythematosus (SLE) does not represent exacerbation of immunologic SLE, and that by implication hypocomplementemia in this setting is likely due to reduced synthesis rather than increased degradation of complement. A new assay, the measurement of C1s-C1r-C1 inhibitor complex (C1s-C1Inh complex), is used as a quantitative measure of complement consumption. With this assay, in preliminary studies, hypocomplementemic pregnant SLE patients with proteinuria have normal values, while hypocomplementemic not pregnant SLE nephritis patients with proteinuria have very abnormal values. Hypocomplementemia (CH50, C3 and C4) is linearly related to C1s-C1Inh complex in not pregnant patients but there is no correlation between complement and C1s-C1Inh complex in pregnant SLE patients. Approximately 60 pregnant SLE patients will undergo serial serological and clinical evaluations through 6 months post-partum to evaluate """"""""flare"""""""" status. Clinical and serological comparisons of pregnant SLE patients will be with SLE not pregnant patients. Studies of antibody to SSA (associated with congenital SLE), and placental and ovarian hormone function will attempt to predict fetal survival. The hormone assays will compare SLE pregnancies with diabetes pregnancies. We predict that pregnant (hypocomplementemic) SLE patients with proteinuria, thrombocytopenia and lupus anticoagulant will have normal C1s-C1Inh complex, and thus will contrast with not pregnant SLE patients. We also predict that fetal survival will be a function of measureable abnormalities in placental or ovarian hormone and/or SSA antibody.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR032929-03
Application #
3156451
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Hospital for Special Surgery
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021

  Publications

Gharavi, E E; Chaimovich, H; Cucurull, E et al. (1999) Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides. Lupus 8:449-55
Gharavi, A E; Pierangeli, S S; Colden-Stanfield, M et al. (1999) GDKV-induced antiphospholipid antibodies enhance thrombosis and activate endothelial cells in vivo and in vitro. J Immunol 163:2922-7
Magid, M S; Kaplan, C; Sammaritano, L R et al. (1998) Placental pathology in systemic lupus erythematosus: a prospective study. Am J Obstet Gynecol 179:226-34
Gharavi, A E; Cucurull, E; Tang, H et al. (1998) Effect of antiphospholipid antibodies on beta(2) glycoprotein I-phospholipid Interaction. Am J Reprod Immunol 39:310-5
Gharavi, A E; Pierangeli, S S (1998) Origin of antiphospholipid antibodies: induction of aPL by viral peptides. Lupus 7 Suppl 2:S52-4
Gharavi, A E; Pierangeli, S S; Gharavi, E E et al. (1998) Thrombogenic properties of antiphospholipid antibodies do not depend on their binding to beta2 glycoprotein 1 (beta2GP1) alone. Lupus 7:341-6
Molina, J F; Gutierrez-Urena, S; Molina, J et al. (1997) Variability of anticardiolipin antibody isotype distribution in 3 geographic populations of patients with systemic lupus erythematosus. J Rheumatol 24:291-6
Molina, J F; Molina, J; Garcia, C et al. (1997) Ethnic differences in the clinical expression of systemic lupus erythematosus: a comparative study between African-Americans and Latin Americans. Lupus 6:63-7
Morse, J H; Barst, R J; Fotino, M et al. (1997) Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. Am J Respir Crit Care Med 155:274-8
Garcia, C O; Kanbour-Shakir, A; Tang, H et al. (1997) Induction of experimental antiphospholipid antibody syndrome in PL/J mice following immunization with beta 2 GPI. Am J Reprod Immunol 37:118-24

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