Background/Purpose:

Vaccinating SLE patients with influenza and pneumococcal vaccines is generally considered safe and effective.  However, conflicting reports regarding the impact of vaccination on autoantibody production exist.  Whether vaccination might facilitate affinity maturation of autoantibody specificities or cause novel specificities to arise is difficult to determine from serum antibody measurements alone. In order to study this question on a per antibody basis, we have isolated and expressed human monoclonal antibodies from SLE patients following vaccination with both the influenza vaccine and Pneumovax23. Our technique utilizes antibody secreting cells arising from a memory response to produce antibodies specific to the vaccine.  Furthermore, in autoimmune donors we can further characterize the antibodies with respect to common autoimmune specificities.

Methods:

We 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 human 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.  We are also capable of reverting the antibodies to their germline configurations to examine the role of somatic hypermutation in their auto-specificities.

Results:

Two interesting antibodies were characterized from two SLE donors, one following vaccination with the influenza vaccine (2_156p1E05) and the other following vaccination with Pneumovax23 (pn134p1D02).  Although antibody 2_156p1E05 does not bind to influenza virus, it is the first example of a fully human high affinity antibody to Sm (8×10^-10M).  By line immunoblot, we show that it binds to SmD.  When reverted to its naïve/germline configuration, this antibody loses all binding to Sm indicating that such binding arose during somatic hypermutation.  Unlike 2_156p1E05, pn134p1D02 does bind to S. pneumoniae serotype 5 polysaccharide with high affinity (2×10^-10M).  However, by line immunoblot, we show that it also binds to nRNP A.     

            The serum of the donor of 2_156p1E05 was also carefully analyzed over a three year period and this patient’s antibody response to Sm clearly affinity matured, increasing in overall affinity in each year.  Since this antibody does not bind influenza, it is unclear whether the vaccine played a role in this maturation, however, pn134p1D02 clearly binds polysaccharide and arose or matured after vaccination with Pneumovax23.

Conclusion:

The ability to analyze the autoimmune response of a patient with SLE after vaccination on a per antibody basis allows us to determine whether new auto-specificities may occur after vaccination.  Although this does not appear to be a common event, the fact that it can occur does indeed indicate that vaccination has the potential to increase autoantibody production and potentially clinical flares in select SLE patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibody-secreting-cells-arising-after-vaccination-of-lupus-patients-may-produce-high-affinity-autoantibodies/