Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Antibodies from Antibody-Secreting Cells Following Vaccination in Patients with Systemic Lupus Erythematosus Are Autoreactive and Polyspecific.
Smith2, Kenneth A., Garman3, Lori, Morris3, Jennifer, Thompson3, Linda, Wilson4, Patrick C., James1, Judith A.
Immunization against Streptococcus pneumoniae and influenza is recommended for patients with systemic lupus erythematosus (SLE), but with vaccination comes the risk of inducing or exacerbating an autoimmune response. Several components of vaccines are well known to induce antibodies that are cross-reactive to self-antigens, including tetanus toxiod which has been reported to induce antibodies to cardiolipin (aCL) or DNA and phosphorylcholine (a component of S. pneumoniae C polysaccharide) which has been reported to induce antibodies to dsDNA. However, the induction of antibodies specific to other SLE autoantigens after immunization remains unclear. Most of the previous studies on vaccine-induced autoreactivity have been done using patient sera; in our study, we sought to examine the physiological autoantibody response to two implicated vaccinations, the yearly influenza vaccine and the S. pneumoniae vaccine (PN), by analyzing the antibody repertoire arising during the immune response through generation of human monoclonal antibodies.
Two SLE patients were vaccinated, with at least 4 weeks between vaccinations, and PBMCs were isolated seven days after each immunization. Vaccine-specific ASCs were isolated as single cells from bulk PBMCs. The VDJ regions of the heavy and light chains of individual ASCs were cloned into vectors and expressed together in mammalian cells as monoclonal antibodies (mAbs). Vaccine-specific (PN polysaccharides or influenza virion) binding and autoreactivity (Ro, La, Sm, nRNP) ELISAs were performed on each mAb. Cloning of mAbs were also performed in four healthy individuals, two receiving the flu vaccine and two receiving PN.
On average, 27 mAbs were produced per individual, about 14 specific to each vaccine. PN-specific antibodies were much more likely to use VH3 genes (81%) than flu-specific antibodies (50%; p = 0.007, Chi-square). Overall, the SLE individuals produced more mAbs reactive against SLE antigens (33% of anti-flu and anti-PN) than control individuals (2.7%). Of the mAbs generated from SLE patients, mAbs specific to PN were more likely to be reactive against the tested SLE antigens (47%) than flu mAbs (12%; p = 0.008, Chi-square with Yate's correction). Remarkably, virtually all of these antibodies cross-react with at least two of the autoantigens tested and many mAbs react to all four. Notably, the polysaccharide antibodies were highly serotype specific yet still bound multiple self-antigens, albeit at affinities several orders of magnitude lower than against the immunogen. While pre-incubation with polysaccharide could inhibit mAb binding to SLE antigens, the converse was not true.
These results suggest that S. pneumoniae and influenza vaccination are both capable of inducing antibodies which are cross-reactive to both vaccine antigens and SLE antigens and can escape selection in SLE individuals. In addition, these results indicate that antibodies monospecific to SLE antigens, particularly Ro and La, are rare in the SLE memory pool.
To cite this abstract, please use the following information:
Smith, Kenneth A., Garman, Lori, Morris, Jennifer, Thompson, Linda, Wilson, Patrick C., James, Judith A.; Antibodies from Antibody-Secreting Cells Following Vaccination in Patients with Systemic Lupus Erythematosus Are Autoreactive and Polyspecific. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :734