Upregulation of Antiphospholipid Antibodies Following Cyclophosphamide Therapy in Patients with Systemic Lupus Erythematosus

PANAYIOTIS G. VLACHOYIANNOPOULOS, SOPHIE P. TOYA, GHIKAS KATSIFIS, ELIAS ZINTZARAS, ATHANASIOS G. TZIOUFAS, and HARALAMPOS M. MOUTSOPOULOS

ABSTRACT.

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).

Conclusion. Our data suggest that CYC therapy might be associated with upregulation of aPL and development of antiphospholipid syndrome despite suppression of SLE activity. (First Release July 15 2008; J Rheumatol 2008;35:1768-75)

Key Indexing Terms:

ANTIPHOSPHOLIPID ANTIBODIES
CYCLOPHOSPHAMIDE
SYSTEMIC LUPUS ERYTHEMATOSUS
UPREGULATION

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From the Department of Pathophysiology, University of Athens School of Medicine, and Laiko University Hospital, Athens; and the Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.

P.G. Vlachoyiannopoulos, MD; S.P. Toya, MD; G. Katsifis, MD; A.G. Tzioufas, MD; H.M. Moutsopoulos, MD, FACP, FRCP, Department of Pathophysiology, University of Athens School of Medicine, and Laiko University Hospital; E. Zintzaras, PhD, Department of Biomathematics, University of Thessaly School of Medicine.

Address reprint requests to Dr. P. Vlachoyiannopoulos, Department of Pathophysiology, University of Athens Medical School, 75, Mikras Asias St, 11527, Athens, Greece. E-mail: pvlah@med.uoa.gr

Accepted for publication April 4, 2008.

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