Exposure of mice to topical bovine thrombin induces systemic autoimmunity.

Journal Article

Bovine thrombin is used as an aid to hemostasis in medical and surgical procedures. At least 500,000 Americans are exposed to this therapeutic annually and reports suggest that exposure is associated with the development of autoreactive antibodies. To determine whether bovine thrombin can induce pathological autoimmunity we exposed nonautoimmune-prone galactose-alpha1-3-galactose-deficient mice to the two bovine thrombin preparations currently approved for use in the United States. We found that, like humans exposed to bovine thrombin, mice developed an immune response against the therapeutic and the xenogeneic carbohydrate galactose-alpha1-3-galactose, and some mice developed autoantibodies against clotting factors. Further, unexpectedly, a single exposure to this therapeutic also induced autoimmunity with features characteristic of systemic lupus erythematosus including antibodies against nuclear antigens, native DNA, double-stranded DNA, and cardiolipin. High levels of these autoantibodies correlated with glomerulonephritis in all mice evaluated. This autoimmune syndrome was detected in mice 15 weeks after a secondary exposure to bovine thrombin and female mice were found to develop the syndrome at a significantly greater frequency than males. Thus, these studies indicate that exposure to bovine thrombin preparations can induce a pathological systemic autoimmune syndrome with lupus-like serology.

Full Text

Duke Authors

Cited Authors

  • Schoenecker, JG; Johnson, RK; Lesher, AP; Day, JD; Love, SD; Hoffman, MR; Ortel, TL; Parker, W; Lawson, JH

Published Date

  • November 2001

Published In

Volume / Issue

  • 159 / 5

Start / End Page

  • 1957 - 1969

PubMed ID

  • 11696457

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)63043-X

Language

  • eng

Conference Location

  • United States