Upregulation of antiphospholipid antibodies following cyclophosphamide therapy in patients with systemic lupus erythematosus.
OBJECTIVE
We have observed several cases of patients with systemic lupus erythematosus (SLE) who developed antiphospholipid antibodies (aPL) or full blown antiphospholipid syndrome (APS) after being successfully treated with cyclophosphamide (CYC). To further evaluate the significance of this phenomenon we undertook a retrospective study of our patient population with SLE.


METHODS
The charts of 320 patients with SLE, either CYC treated (n = 117) or non-treated (n = 203), were reviewed. The disease activity over time was evaluated using the European Consensus Lupus Activity Measurement (ECLAM) scoring system, as well as initial and cumulative anti-dsDNA antibody titers and C3, C4 complement levels. aPL titers (IgG and IgM) were documented for all patients. Seroconversion was defined as the de novo appearance of aPL antibodies at a titer higher than the 99th percentile of 100 normal sera, tested on 2 occasions 12 weeks apart.


RESULTS
Seroconversion occurred in 22 out of 117 patients treated with CYC as compared with 2 out of 203 non-CYC treated patients [odds ratio (OR) = 23.27, 95% confidence interval (CI) 5.36-101.01]. Six patients from the seroconverted CYC treated group were diagnosed with APS compared to none in the non-CYC treated group. The association between seroconversion and CYC remained significant after adjustment for ECLAM score after treatment, prednisone dose and disease duration (OR = 13.4, 95% CI 2.67-67.50). Seroconversion occurred despite successful disease remission as judged by significant decrease of: anti-dsDNA antibody titers (p < 0.01), ECLAM scores (p < 0.01), and C3 (p < 0.01) and C4 levels (p < 0.01).


CONCLUSIONS
Our data suggest that CYC therapy might be associated with upregulation of aPL and development of antiphospholipid syndrome despite suppression of SLE activity.
Vlachoyiannopoulos
Panayiotis G
PG
Department of Pathophysiology, University of Athens School of Medicine, Athens, Greece. pvlah@med.uoa.gr
Toya
Sophie P
SP
Katsifis
Ghikas
G
Zintzaras
Elias
E
Tzioufas
Athanasios G
AG
Moutsopoulos
Haralampos M
HM
D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
D017152:Antibodies, Antiphospholipid; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide