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.


CONCLUSIONS
Ki antigen contains multiple epitopes recognized by autoimmune sera. Autoantibody profiles revealed distinctive immune responses, associated with certain clinical subtypes.
Matsudaira
Ran
R
Department of Internal Medicine and Rheumatology, Juntendo University, School of Medicine, Tokyo, Japan.
Takeuchi
Ken
K
Takasaki
Yoshinari
Y
Yano
Tetsuro
T
Matsushita
Masakazu
M
Hashimoto
Hiroshi
H
D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens; D015153:Blotting, Western; D000939:Epitopes / Q000276:immunology; D017353:Gene Deletion; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D009124:Muscle Proteins; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; C099558:Ki antigen; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D046988:Proteasome Endopeptidase Complex