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Evidence for proteolytic cleavage of covalently bound protein A from a silica based extracorporeal immunoadsorbent and lack of relationship to treatment effects.
- Source :
-
Transfusion science [Transfus Sci] 1995 Mar; Vol. 16 (1), pp. 85-94. - Publication Year :
- 1995
-
Abstract
- Studies were conducted to evaluate the potential cause for release of covalently bound Staphylococcal protein A (SpA) from a silica based extracorporeal immunoadsorbent matrix. In vitro tests revealed that SpA could be detected in human plasma, human serum, and chicken serum upon exposure to the immunoadsorbent matrix which had been treated to remove non-covalently bound SpA. In contrast, only minute quantities of SpA were detected after exposure of a physiologic mixture of purified albumin and immunoglobulin G (IgG) to the immunoadsorbent matrix. Additional tests, employing a cocktail of protease inhibitors and formalin as a general stabilizer and protease inhibitor, revealed significant inhibition of endogenous proteolytic activity present in plasma and serum. Prevention of this proteolytic activity also significantly inhibited the release of covalently bound SpA from the immunoadsorbent matrix upon contact with plasma or serum samples. Further analyses of serum samples from patients with immune thrombocytopenia, chemotherapy associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, and breast cancer revealed a lack of association between the quantity of SpA proteolytically released and observed clinical responses or adverse effects experienced during immunoadsorption treatments. These studies indicate that SpA detected in plasma or serum after exposure to the immunoadsorbent is due to inherent endogenous proteolytic activity which cleaves protein fragments from the matrix and that these cleaved SpA fragments do not appear to contribute to the observed clinical responses or adverse effects in treated patients.
- Subjects :
- Animals
Antigen-Antibody Complex blood
Autoantibodies blood
Autoimmune Diseases blood
Autoimmune Diseases therapy
Chickens blood
Formaldehyde pharmacology
Hemolytic-Uremic Syndrome blood
Hemolytic-Uremic Syndrome therapy
Humans
Immunoglobulin G blood
Immunosuppression Therapy methods
Plasma
Protease Inhibitors pharmacology
Purpura, Thrombocytopenic, Idiopathic blood
Purpura, Thrombocytopenic, Idiopathic therapy
Silicon Dioxide
Staphylococcal Protein A blood
Treatment Outcome
Chromatography, Affinity methods
Endopeptidases blood
Extracorporeal Circulation methods
Immunosorbent Techniques
Staphylococcal Protein A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0955-3886
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Transfusion science
- Publication Type :
- Academic Journal
- Accession number :
- 10155709
- Full Text :
- https://doi.org/10.1016/0955-3886(94)00064-q