THE SPINDLE KINESIN-LIKE PROTEIN HSEG5 IS AN AUTOANTIGEN IN SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. Autoantibodies directed against the mitotic spindle apparat us (MSA) have been shown to target an antigen referred to as NuMA (nuc lear mitotic apparatus), In this study, we identified a second MSA ant igen as the spindle kinesin-like protein HsEg5, We studied the frequen cy of antibodies to HsEg5 in human sera that demonstrate the MSA patte rn of staining, the frequency of autoantibodies to HsEg5 in patients w ith systemic lupus erythematosus (SLE), and the clinical features of p atients with antibodies to HsEg5. Methods. A prototype serum from an S LE patient was used to isolate a 4.8-kilobase complementary DNA (cDNA) from a HeLa cDNA library, Western blot, immunoprecipitation, and sequ ence analysis revealed that the antigen was an similar to 130-kd prote in, HsEg5, The frequency of autoantibodies to recombinant HsEg5 in 51 sera that demonstrated an MSA pattern of staining on HEp-2 and HeLa ce lls was detected by immunoblotting 2 constructs of the cDNA, The clini cal features of patients with antibodies directed against HsEg5 was ob tained by retrospective chart review. Results. The antigen responsible for the MSA-35 pattern was identified as the human kinesin-like prote in HsEg5, Seven of 51 sera (14%) that demonstrated an MSA pattern of s taining reacted with recombinant HsEg5, Six of 7 of the HsEg5-positive patients (86%) had SLE, and 1 had Sjogren's syndrome, The indirect im munofluorescent staining pattern of sera that reacted with HsEg5 could be distinguished from the other sera that reacted with NuMA, In an un selected cohort of 52 SLE patients, 3 (6%) had autoantibodies reactive with the recombinant HsEg5. Conclusion. Autoantibodies to MSA fall in to 2 major classes: those reactive with NuMA and those reactive with H sEg5, Autoantibodies to HsEg5 are found in a lower frequency than NuMA in sera that demonstrate the MSA pattern of staining and appear to be specifically associated with SLE, HsEg5 can be distinguished from NuM A by indirect immunofluorescence and Western blotting.