Abstract
Plasma samples obtained from a patient 6 wk, 6 months, and 4 yr after recovery from anti-VIII:C (anti-hemophilic factor, where VIII:C = factor VIII procoagulant activity) autoimmune disease were found to contain antibodies that inhibited anti-VIII:C activity in the patient's prerecovery plasma and in the plasma of two other patients with anti-VIII:C autoantibodies. F(ab')2 fragments from postrecovery IgG suppressed anti-VIII:C activity in F(ab')2 fragments from prerecovery IgG within a narrow range of molar ratios. Anti-VIII:C activity in F(ab')2 autoantibodies was also inhibited by F(ab')2 fragments from polyspecific therapeutic immunoglobulins prepared from a large pool of normal donors (IVIg). IgG from prerecovery plasma bound to F(ab')2 from postrecovery IgG and to F(ab')2 from IVIg, as assessed by ELISA. Affinity chromatography experiments demonstrated that F(ab')2 from postrecovery IgG preferentially bound anti-VIII:C antibodies among F(ab')2 fragments from prerecovery plasma containing anti-VIII:C autoantibodies. F(ab')2 from prerecovery plasma bound in higher amounts to postrecovery F(ab')2 than to IVIg. Insolubilized F(ab')2 fragments from postrecovery plasma also bound F(ab')2 fragments prepared from the plasma of another patient with anti-VIII:C autoimmune disease, although in lesser amounts than the patient's own prerecovery anti-VIII:C F(ab')2 antibodies. These observations suggest that human anti-VIII:C autoantibodies share idiotypic determinants and that spontaneous recovery from anti-VIII:C autoimmune disease occurs through idiotypic suppression of autoantibodies. In patients who recover from autoimmune disease and in patients in whom autoantibodies have been suppressed by infusions of IVIg, antiidiotypic antibodies, possibly by providing internal images of the antigen, may have shifted the immune system toward the steady-state equilibrium that prevents autoimmunity in normal individuals.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Biggs R., Austen D. E., Denson K. W., Borrett R., Rizza C. R. The mode of action of antibodies which destroy factor VIII. II. Antibodies which give complex concentration graphs. Br J Haematol. 1972 Aug;23(2):137–155. doi: 10.1111/j.1365-2141.1972.tb03468.x. [DOI] [PubMed] [Google Scholar]
- Biggs R., Austen D. E., Denson K. W., Rizza C. R., Borrett R. The mode of action of antibodies which destroy factor VIII. I. Antibodies which have second-order concentration graphs. Br J Haematol. 1972 Aug;23(2):125–135. doi: 10.1111/j.1365-2141.1972.tb03467.x. [DOI] [PubMed] [Google Scholar]
- Green D., Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981 Jun 30;45(3):200–203. [PubMed] [Google Scholar]
- Jerne N. K. Idiotypic networks and other preconceived ideas. Immunol Rev. 1984 Jun;79:5–24. doi: 10.1111/j.1600-065x.1984.tb00484.x. [DOI] [PubMed] [Google Scholar]
- Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
- Letter: A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh. 1975 Dec 15;34(3):869–872. [PubMed] [Google Scholar]
- Matsuyama T., Fukumori J., Tanaka H. Evidence of unique idiotypic determinants and similar idiotypic determinants on human antithyroglobulin antibodies. Clin Exp Immunol. 1983 Feb;51(2):381–386. [PMC free article] [PubMed] [Google Scholar]
- Rajewsky K., Takemori T. Genetics, expression, and function of idiotypes. Annu Rev Immunol. 1983;1:569–607. doi: 10.1146/annurev.iy.01.040183.003033. [DOI] [PubMed] [Google Scholar]
- Sultan Y., Kazatchkine M. D., Maisonneuve P., Nydegger U. E. Anti-idiotypic suppression of autoantibodies to factor VIII (antihaemophilic factor) by high-dose intravenous gammaglobulin. Lancet. 1984 Oct 6;2(8406):765–768. doi: 10.1016/s0140-6736(84)90701-3. [DOI] [PubMed] [Google Scholar]