Anti-SSA antibodies are present in immunoglobulin preparations.
BACKGROUND
Anti-SSA autoantibodies are among the most frequently detected autoantibodies and have traditionally been associated with Sjögren's syndrome (SjS) and systemic lupus erythematosus. The unexpected finding of anti-SSA antibodies in a patient with common variable immunodeficiency disorder (CVID) treated with intravenous immunoglobulin (IVIG), who developed discoid lupus erythematosus, prompted us to investigate the presence of anti-SSA antibodies in IVIG preparations. Since anti-SSA antibodies may be present in apparently healthy individuals without overt autoimmune features, IVIG preparations may also contain anti-SSA antibodies.


METHODS
IVIG consists of polyclonal immunoglobulin G isolated from the plasma of more than 1000 blood donors. Several IVIG batches from different suppliers and serum samples of patients receiving these IVIG products were tested for the presence of anti-nuclear antibodies (ANAs) and extractable nuclear antibodies (ENAs). In addition, we tested several plasma pools for the presence of anti-SSA and subsequent serum samples of individual donors.


RESULTS
Several CVID-patients receiving IVIG tested positive for ANA and anti-SSA. The IVIG products administered also contained clearly detectable concentrations of these antibodies. The frequency of apparently healthy blood donors with anti-SSA positivity was 0.69% and one of 1894 donors (0.05%) showed a very high titer of anti-SSA of more than 10,000 U/mL.


CONCLUSIONS
Anti-SSA is present in IVIG products and in blood donors without clinical symptoms. IVIG replacement can interfere with ANA and ENA serology by passive transfer of autoantibodies. We hypothesize that such autoantibodies may be causally related to disease manifestations in some recipients.
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands.
Renate G
http://orcid.org/0000-0003-3113-6587
RG
van der Molen
Department of Immunopathology and Blood Coagulation, Sanquin Diagnostic Services, Amsterdam, the Netherlands.
Dörte
D
Hamann
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands.
Joannes F M
JF
Jacobs
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands.
Arnold
A
van der Meer
Department of Immunopathology and Blood Coagulation, Sanquin Diagnostic Services, Amsterdam, the Netherlands.
Jan
J
de Jong
Sanquin Blood Supply Foundation, Amsterdam, the Netherlands.
Christine
C
Kramer
Sanquin Blood Supply Foundation, Amsterdam, the Netherlands.
Paul F W
PF
Strengers
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Jos W M
JW
van der Meer
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D001782:Blood Donors; D017074:Common Variable Immunodeficiency / Q000628:therapy*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000276:immunology; D008179:Lupus Erythematosus, Discoid / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012261:Ribonucleoproteins / Q000276:immunology*; D055815:Young Adult; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D016756:Immunoglobulins, Intravenous; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C035356:SS-A antibodies