Relationships between autoantibody responses to deletion mutants of Ki antigen and clinical manifestations of lupus.

OBJECTIVE: To determine the relationships between subtypes of anti-Ki antibodies and clinical manifestations of systemic lupus erythematosus.
METHODS: The cDNA encoding full-length bovine Ki antigens or N- or C-terminal fragments were produced by polymerase chain reaction, and the fragments of Ki antigen were expressed as GST fusion proteins. Immunoreactivities of anti-Ki antibodies were tested by Western blotting.
RESULTS: Of 60 sera reactive with full-length Ki antigen (KiF), 21 sera recognized only KiF. KiC5, a fragment containing the last 69 C-terminal amino acids, was recognized by 23 sera. Since no significant difference was observed in prevalence of reactivities between fragments from KiC2 to KiC5, a domain within the last 69 C-terminal amino acids was suggested to be the most common antigenic domain expressed among the GST fusion proteins. All 11 sera reacting with a fragment containing the initial 81 N-terminal amino acids also recognized all other fragments. A domain homologous to SV40 nuclear localization signal was required for N-terminal recognition by 8 sera. Reactivity to the last 69 C-terminal amino acids and the initial 81 N-terminal amino acids showed specificities to systemic lupus erythematosus without and with Sjögren's syndrome, respectively. Sicca was significantly more prevalent in patients whose sera reacted with both N- and C-terminal fragments, while prevalence of anti-SSA/Ro antibody was low.
CONCLUSION: Ki antigen contains multiple epitopes recognized by autoimmune sera. Autoantibody profiles revealed distinctive immune responses, associated with certain clinical subtypes.