Presence of autoantibodies to peptidyl-prolyl cis-trans isomerase (cyclosporin A-binding protein) in systemic lupus erythematosus.
Several autoantibodies against cytoplasmic or nuclear components of cells have been reported in autoimmune diseases. We report here a previously unrecognized autoantibody to peptidyl-prolyl cis-trans isomerase (PPIase) in patients with systemic lupus erythematosus (SLE). PPIase, which catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides, has recently been found to be identical to cyclophilin, a specific binding protein of a potent immunosuppressant, cyclosporin A. IgG and IgM anti-PPIase antibodies were detected in 40 and 20% of unselected patients with SLE, respectively, by ELISA. The reactivity of these sera was confirmed by immunoblotting experiments. Sera from rheumatoid arthritis patients showed no reactivity and 1 of 8 sera from systemic sclerosis patients and 1 of 25 sera from normal controls showed only weak reactivity. Unexpectedly, the anti-PPIase antibody was unable to inhibit PPIase activity, indicating that the autoantibody recognizes an epitope of PPIase which is different from the active site of PPIase. The levels of the anti-PPIase antibody in SLE patients correlated with remissions and flares of the disease. The anti-PPIase antibody was higher in patients with active SLE than those with inactive disease. The prevalence of the active stage of the disease was significantly higher in IgG anti-PPIase antibody-positive SLE patients as compared to antibody-negative SLE patients. These data define the presence of a new autoantibody against PPIase and its association with the activity and certain clinical manifestations in SLE.
Harigai
M
M
Institute of Rheumatology, Tokyo Women's Medical College, Japan.
Hara
M
M
Takahashi
N
N
Kitani
A
A
Hirose
T
T
Suzuki
K
K
Kawakami
M
M
Hidaka
T
T
Kawaguchi
Y
Y
Ishizuka
T
T
D000328:Adult; D000591:Amino Acid Isomerases / Q000276:immunology* / Q000302:isolation & purification; D001323:Autoantibodies / Q000096:biosynthesis*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology* / Q000302:isolation & purification; D002848:Chromatography, DEAE-Cellulose; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000302:isolation & purification; D007075:Immunoglobulin M / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019696:Peptidylprolyl Isomerase; D013997:Time Factors
D001323:Autoantibodies; D002352:Carrier Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase