Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Antibody Secreting Cells Arising After Vaccination From Anti-Cardiolipin Positive Individuals Can Produce Antibodies Which Are Bi-Specific and Bind to Both Cardiolipin and the Vaccinating Antigen.
Smith1, Kenneth, Muther1, Jennifer, Duke1, Angie, McKee1, Emily, Wilson2, Patrick C., James3, Judith A.
While it is well known that certain bacterial infections may cause the presence of serum anti-cardiolipin antibodies in healthy controls, no one has previously dissected the presence of such antibodies on a 'per-antibody' basis. To this end, we have made antibodies from a serum anti-cardiolipin (aCl) positive, but otherwise healthy individual after three separate vaccinations. These antibodies bind to the vaccinating agent as expected, however, several also bind to cardiolipin.
The OMRF Human Antibody Core Facility has developed a technology that allows us to make fully human monoclonal antibodies from any antigen currently approved as a vaccination in humans. This allows us to make large numbers of fully human full-length monoclonal antibodies which are highly specific to the vaccine antigen(s). This technology is based on the discovery of a population of B cells (ASCs), which arise 7 days after vaccination and produce antibody that is specific for the vaccine antigen. These cells can be sorted and their antibody genes cloned to express the antigen-specific antibody from each ASC.
From this donor, we have characterized 49 antibodies to Streptococcus pneumoniae polysaccharides after vaccination with Pneumovax®23, 11 antibodies to S-OIV after vaccination with the monovalent swine flu vaccine, and 9 antibodies to VZV after vaccination with Zostavax®. Of the S. pneumoniae antibodies, two clonally related antibodies to cell wall polysaccharide, as well as an impressive clonal family of 7 antibodies to serotype 18C bind to cardiolipin (18%). Only one S-OIV antibody also binds to cardiolipin (9%), however it has a remarkable affinity of 8×10-9M. Three VZV antibodies also bind to cardiolipin (33%).
All of the cardiolipin positive antibodies from this donor were also characterized using b2-GPI and qualitative ELISAs to other APS antigens (AESKU APS-Profil-GM kit). Although this donor's serum is not positive for b2-GPI antibodies, two VZV antibodies are weakly positive for b2-GPI. One of these two antibodies also showed clear binding to phosphatidyl-ethanolamine.
The ability to analyze the immune response of a serum aCl positive individual on a 'per-antibody' basis indicates that it is possible in "healthy" and likely autoimmune patients for antigen specific antibodies to also bind to auto-antigen and such antibodies may arise after immune responses to a variety of immunogens.
To cite this abstract, please use the following information:
Smith, Kenneth, Muther, Jennifer, Duke, Angie, McKee, Emily, Wilson, Patrick C., James, Judith A.; Antibody Secreting Cells Arising After Vaccination From Anti-Cardiolipin Positive Individuals Can Produce Antibodies Which Are Bi-Specific and Bind to Both Cardiolipin and the Vaccinating Antigen. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1741