Relapse of systemic lupus erythematosus

Abstract

Ann E Traynor and colleagues (Aug 26, p 701)1Traynor AE Schroeder J Rosa RM et al.Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study.Lancet. 2000; 356: 701-707Summary Full Text Full Text PDF PubMed Scopus (217) Google Scholar report on the efficacy of high-dose chemotherapy and haemopoietic stem-cell transplantation (HSCT) in patients with refractory systemic lupus erythematosus (SLE). In follow-up of 12–40 months no relapse was described. We studied three patients with refractory SLE (follow-up 20–28 months, and have seen a clinical relapse in one man aged 39 years, 18 months after HSCT.2Rosen O Thiel A Massenkeil G et al.Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells.Arthritis Res. 2000; 2: 327-336Crossref PubMed Scopus (80) Google Scholar The patient had developed multiple-organ manifestations over 11 years and he received HSCT for persistent active disease with severe lupus nephritis (WHO class IV) expressing nephrotic syndrome, high titres of antibodies to double stranded, DNA, and low C3 and C4 concentrations despite pulses of methylprednisolone and intravenous cyclophosphamide. After HSCT, clinical symptoms resolved for the first time, autoantibodies became negative, and the complement concentrations became normal. Accordingly, the score of the disease activity index SLE daily activity index was zero at that time. 15 months after HSCT the antinuclear antibodies remained negative (> 1:160). However, at 18 months after HSCT, lupus-nephritis and erythema had reoccurred, probably triggered by sun exposure. Simultaneously, a striking increase of autoantibody titres and decline in complement concentrations were noted (table).TableCourse of activity parametersFollow-up after HSCTSLED daily activityANAComplement concentrationC3 (mg/dL)C4 (mg/dL)0 months241:256044<5·012 months01:1601022218 months161:512032521 months241:10240245*ELISA cut-off was 118 IU/mL. ANA=antinuclear antibodies. Open table in a new tab *ELISA cut-off was 118 IU/mL. ANA=antinuclear antibodies. At 21 months after HSCT, lupus activity remains uncontrolled despite high doses of steroids and monthly cycles of intravenous cyclophosphamide reflected by a further impairment of proteinuria and renal function (table). Since the treatment has failed we have decided to restart an immunoablative regimen. We agree with Traynor and colleagues' conclusion that HSCT can be effective in selected patients, since the two other patients from our trial have been in continuous remission for 25 months and 28 months, respectively. HSCT is a novel experimental approach for treating patients with refractory autoimmune diseases. Preliminary data suggest that, especially in SLE patients, long-term remissions can be achieved. Nevertheless, disease can recur and may not respond to conventional immunosuppressive treatment. To date, factors influencing the duration of remission remain obscure. Our patient who relapsed had a very high disease activity at the onset of mobilisation. Thus, we speculate that, besides a person's sex, disease activity could be a risk factor for relapse. Long-term follow-up is needed to distinguish transient increases of antinuclear antibodies from incipient relapses. Resetting of the immune system after HSCT and the development of tolerance might not be permanent. We speculate that autoreactive lymphocyte subpopulations will survive an immunoablative regimen. Therefore, exogenous triggers, such as sun exposure in our patient, might reactivate SLE. Relapse of systemic lupus erythematosusAuthors' reply Full-Text PDF