Autoantibody to hLSm4 and the heptameric LSm complex in anti-Sm sera.
OBJECTIVE
To characterize the 15-kd human SmD-like autoantigen and its associated proteins previously shown to be recognized by IgM antibodies in patients with Epstein-Barr virus (EBV)-induced infectious mononucleosis.


METHODS
The full-length complementary DNA for the 15-kd protein was expressed as recombinant protein and analyzed for reactivity using biochemical analysis and immunoprecipitation (IP).


RESULTS
The 15-kd protein was determined to be the human like-Sm protein LSm4 (hLSm4). Rabbit antibody raised against the C-terminal polypeptide immunoprecipitated a 68-kd complex composed of LSm4 together with a group of smaller proteins ranging in size from 6.5 to 14 kd, consistent with the reported heptameric LSm complexes involved in U4/U6 duplex formation and messenger RNA (mRNA) decapping/degradation. About 80% of all anti-Sm sera from patients with systemic lupus erythematosus (SLE) recognized the hLSm4 in vitro translated product, while 6.7% (29 of 434) immunoprecipitated from cell extracts hLSm4 together with the other members of the hLSm complex. Four sera (0.92%) showed apparently exclusive reactivity to the hLSm complex in the absence of reactivity to Sm core proteins in the IP assay.


CONCLUSIONS
These findings document that while IgM, but not IgG, autoantibodies to LSm4 were found in sera from patients with EBV infection, IgG autoantibodies to hLSm4 are detected in a large number of anti-Sm-positive sera from patients with SLE. Importantly, in a small number of anti-Sm sera the LSm complex can be recognized independently of the Sm core protein antigens. Our data introduce the concept that "Sm" autoantigens include Sm as well as LSm complexes involved in the maturation and degradation of mRNA.
Eystathioy
Theophany
T
Scripps Research Institute, La Jolla, California 92037, USA.
Peebles
Carol L
CL
Hamel
John C
JC
Vaughn
John H
JH
Chan
Edward K L
EK
D000595:Amino Acid Sequence / Q000235:genetics; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence / Q000235:genetics; D002460:Cell Line; D002850:Chromatography, Gel; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes; D006367:HeLa Cells; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology* / Q000378:metabolism; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; D000939:Epitopes; D007106:Immune Sera; C485751:LSM4 protein, human; D011506:Proteins; D017411:Ribonucleoproteins, Small Nuclear; C526412:SNRPD3 protein, human; D055517:snRNP Core Proteins