Prospective Immunological Assessment of Arthritis Induced by Rubella Vaccine

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Abstract
A prospective study was carried out to correlate the development of joint symptoms after rubella immunization with pre- and post-immunization rubella-specific immunological responses. Arthralgia or arthritis or both occurred in 10 of 37 adult female volunteers at a mean time of 17.0 days after immunization with the RA 27/3 rubella vaccine. All individuals studied before immunization were seronegative for rubella by either the hemagglutination inhibition or the single radial hemolysis technique. In contrast, rubella enzyme-linked immunosorbent assay or lymphoproliferative responses or both were positive in 27 of 37 (73%) individuals tested before receiving the vaccine. Rubella enzyme-linked immuno-sorbent assays carried out before immunization were positive at high levels (mean E = 0.536) in four individuals who developed recurrent episodes of arthritis after administration of the vaccine while remaining at low levels preimmunization in subjects who developed transient arthralgia (E = 0.238) or no joint manifestations at all (E = 0.288). These data provide preliminary evidence suggesting that rubella vaccine-associated arthritis may occur as a consequence of secondary, rather than primary, infection with rubella virus and that the presence of circulating, nonneutralizing rubella antibody may enhance the development or severity (or both) of the associated postinfection joint manifestations. Assessment of rubella hemagglutination inhibition, hemagglutination inhibition (immunoglobulin M), and enzyme-linked immunosorbent assay serological responses at 6 weeks and 6 months post-immunization revealed no significant differences between patients who developed and those who did not develop joint manifestations. Rubella lymphoproliferative responses were elevated at 6 weeks post-immunization in the group developing arthralgia or arthritis or both, with no difference between the groups observed at 6 months post-immunization.