The BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome

Mason, A.N., Harmer, I. and Mackworth-Young, C.G. 1999. The BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome. Lupus. 8 (3), pp. 234-239.

TitleThe BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome
AuthorsMason, A.N., Harmer, I. and Mackworth-Young, C.G.
Abstract

Background: A human IgM monoclonal anticardiolipin antibody–BH1–has previously been described, which has characteristics typical of antiphospholipid antibodies in the serum of patients with antiphospholipid syndrome (APS). It appears to be idiotypically distinct from other human monoclonal autoantibodies of different or overlapping ligand-binding specificities derived from patients with related conditions.

Aim: To determine whether the idiotype of BH1 is expressed on particular populations of antibodies (antiphospholipid and anti-β2-glucoprotein I) in the serum of patients with APS and other conditions.

Methods: Sera from patients with APS (9), systemic lupus erythematosus without APS (`uncomplicated SLE'–9), and rheumatoid arthritis (RA–15), and from normal controls (15) were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with cardiolipin, β2 glycoprotein I (β2 GPI), and a polyclonal anti-idiotype raised against BH1 (RIdBH1). Absorption experiments were subsequently performed on selected sera using micelles of cardiolipin or phosphatidyl choline.

Results: Eight out of nine patients with APS were positive for binding to RIdBH1 (IgG and/or IgM), while only one patient with uncomplicated SLE and none of the patients with RA or the healthy controls were positive. Although all of the patients with APS were positive for binding to β2 GPI, there was poor correlation between these results and levels of binding to cardiolipin and RIdBH1. Absorption of sera from patients with APS by cardolipin micelles resulted in a median reduction in IgG anticardiolipin and anti-β2 GPI activity of 81.6% and 6.3% respectively. For those sera positive for IgG reactivity with RIdBH1 the median reduction in this activity was 79.4%. Antibodies eluted from selected micelles showed activity against cardiolipin, β2 GPI and RIdBH1. Three anticardiolipin-positive sera from patients with RA were similarly absorbed; however the eluted antibodies failed to bind to RIdBH1. Absorption of all these sera with phosphatidyl choline resulted in no significant reduction in any of these activities.

Conclusions: The BH1 idiotype defines a population of serum antibodies associated with features of APS. The antibody response in this condition, though diverse, may include the expression of a restricted group of variable region genes.

JournalLupus
Journal citation8 (3), pp. 234-239
ISSN0961-2033
Year1999
PublisherSage
Digital Object Identifier (DOI)doi:10.1191/096120399678847687
Publication dates
PublishedMar 1999

Related outputs

Molecular characterization of the variable domains of an αIIbβ3-specific immunoglobulin M κ platelet cold agglutinin in a follicular lymphoma patient with treatment refractory autoimmune thrombocytopenia: idiotypic overlap between αIIbβ3 integrin antibodies
Jennings, N.S., Harmer, I., Campbell, K., Stafford, P., Smith, G.A., Metcalfe, P., Benton, M.A., Marsh, J.C.W. and Ouwehand, W.H. 2007. Molecular characterization of the variable domains of an αIIbβ3-specific immunoglobulin M κ platelet cold agglutinin in a follicular lymphoma patient with treatment refractory autoimmune thrombocytopenia: idiotypic overlap between αIIbβ3 integrin antibodies. Transfusion. 47 (3), pp. 499-510.

Production of calmodulin-tagged proteins in Drosophila Schneider S2 cells: a novel system for antigen production and phage antibody isolation
Jennings, N.S., Smethurst, P.A., Knight, G., O'Connor, M.N., Joutsi-Korhonen, L., Stafford, P., Stephens, J., Garner, S.F., Harmer, I., Farndale, R.W., Watkins, N.A. and Ouwehand, W.H. 2006. Production of calmodulin-tagged proteins in Drosophila Schneider S2 cells: a novel system for antigen production and phage antibody isolation. Journal of Immunological Methods. 316 (1-2), pp. 75-83.

Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms
Watkins, N.A., O'Connor, M.N., Rankin, A., Jennings, N.S., Wilson, E., Harmer, I., Davies, L., Smethurst, P.A., Dudbridge, F., Farndale, R.W. and Ouwehand, W.H. 2006. Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms. Journal of Thrombosis and Haemostasis. 4 (6), pp. 1197-1205.

Platelet integrin α 2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display
Hughes, D.L., Stafford, P., Hamaia, S.W., Harmer, I., Schoolmeester, A., Deckmyn, H., Farndale, R.W., Ouwehand, W.H. and Watkins, N.A. 2005. Platelet integrin α 2 I-domain specific antibodies produced via domain specific DNA vaccination combined with variable gene phage display. Thrombosis and Haemostasis. 94 (16), pp. 1318-1326.

The role of antigen in the selection of the human V3-23 immunoglobulin heavy chain variable region gene
Mackworth-Young, C.G., Harmer, I. and Mageed, R.A. 2003. The role of antigen in the selection of the human V3-23 immunoglobulin heavy chain variable region gene. Clinical and Experimental Immunology. 134 (3), pp. 420-425.

Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region
Mageed, R.A., Harmer, I., Wynn, S.L., Moyes, S.P., Maziak, B.R., Bruggemann, M. and Mackworth-Young, C.G. 2001. Rearrangement of the human heavy chain variable region gene V3-23 in transgenic mice generates antibodies reactive with a range of antigens on the basis of VHCDR3 and residues intrinsic to the heavy chain variable region. Clinical and Experimental Immunology. 123 (1), pp. 1-8.

Chimaeric monoclonal antibodies encoded by the human VH26 gene from naive transgenic mice display a wide range of antigen binding specificities
Harmer, I., Mageed, R.A., Kaminski, A., Charles, P., Bruggemann, M. and Mackworth-Young, C.G. 1996. Chimaeric monoclonal antibodies encoded by the human VH26 gene from naive transgenic mice display a wide range of antigen binding specificities. Immunology. 88 (2), pp. 174-182.

Phospholipid binding specificities and idiotype expression of hybridoma derived monoclonal autoantibodies from splenic cells of patients with systemic lupus erythematosus
Ravirajan, C.T., Harmer, I., McNally, T., Hohmann, A., Mackworth-Young, C.G. and Isenberg D, A. 1995. Phospholipid binding specificities and idiotype expression of hybridoma derived monoclonal autoantibodies from splenic cells of patients with systemic lupus erythematosus. Annals of the Rheumatic Diseases. 54 (6), pp. 471-476.

Endothelium-derived haemostatic factors and the antiphospholipid syndrome
Mackworth-Young, C.G., Andreotti, F., Harmer, I., Loizou, S., Pottinger, B.E., Pearson, J.D., Maseri, A. and Walport M, J. 1995. Endothelium-derived haemostatic factors and the antiphospholipid syndrome. British Journal of Rheumatology. 34, pp. 201-206.

A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded
Harmer, I., Loizou, S., Thompson, K., So, A.K., Walport M, J., Mackworth-Young, C.G. and A. K. So 1995. A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded. Arthritis and Rheumatism. 38, pp. 1068-1076.

The FITC-anti-FITC system is a sensitive alternative to biotin-streptavidin in ELISA
Harmer, I. and Samuel, D. 1989. The FITC-anti-FITC system is a sensitive alternative to biotin-streptavidin in ELISA. Journal of Immunological Methods. 122 (1), pp. 115-121.

Structural and idiotypic relationships between monoclonal antibodies specific for IgG1 (Fc) subclass epitopes
Harmer, I. and Jefferis, R. 1988. Structural and idiotypic relationships between monoclonal antibodies specific for IgG1 (Fc) subclass epitopes. Biochemical Society Transactions. 16 (5), pp. 747-8.

Permalink - https://westminsterresearch.westminster.ac.uk/item/9v68x/the-bh1-idiotype-defines-a-population-of-anticardiolipin-antibodies-closely-associated-with-the-antiphospholipid-syndrome


Share this
Tweet
Email