Immunization with vesicular stomatitis virus nucleocapsid protein induces autoantibodies to the 60 kD Ro ribonucleoprotein particle.
BACKGROUND
Systemic lupus erythematosus (SLE) is an autoimmune disorder of unknown etiology that is characterized by antibodies binding ribonucleoprotein complexes. The epitopes of SLE associated 60 kd Ro (or SSA) autoantigen share sequence with vesicular stomatitis virus (VSV) nucleocapsid (N) protein and SLE patients with anti-Ro are more likely to bind the N-protein than anti-Ro negative patients.


METHODS
We immunized New Zealand white (NZW) rabbits with purified VSV N-protein to examine the relationship between the immune response to N-protein and anti-Ro.


RESULTS
After multiple immunizations with VSV N-protein, NZW rabbits produced not only IgG antibodies to VSV N-protein but also an autoimmune response to Ro antigen. The IgG fraction of the rabbit immune serum precipitates 60 kd Ro protein as well as its associated Y RNAs. Antibodies elicited by 10 immunizations of VSV N-protein bind to at least 20 linear epitope groups on VSV N-protein and over 25 linear epitope groups on 60 kd Ro protein. These antibodies also bound 5 of the 6 shared sequences between 60 kd Ro protein and VSV N-protein.


CONCLUSIONS
Our data demonstrate that an immune response initiated towards a foreign antigen, selected on the basis of sharing short sequence similarity with the autoantigenic epitopes of an autoantigen, can lead to an autoimmune response.
Huang
S C
SC
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Pan
Z
Z
Kurien
B T
BT
James
J A
JA
Harley
J B
JB
Scofield
R H
RH
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D015151:Immunoblotting; D011233:Precipitin Tests; D020733:RNA, Small Cytoplasmic; D011817:Rabbits; D012261:Ribonucleoproteins / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D014758:Viral Core Proteins; D000099207:SS-A Antigen; C116006:RO60 protein, human