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Rapid improvement of SLE-specific cutaneous lesions by C1q immunoadsorption
  1. B BERNER,
  2. A K SCHEEL,
  3. V SCHETTLER,
  4. K M HUMMEL,
  5. M A REUSS-BORST,
  6. G A MÜLLER
  1. Department of Nephrology and Rheumatology
  2. Georg-August-University Göttingen
  3. Germany
  4. Department of Dermatology
  5. Georg-August-University Göttingen
  6. Germany
  7. Fresenius HemoCare Adsorber Technology GmbH
  8. St Wendel, Germany
  1. Dr B Berner, Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
  1. E OESTMANN
  1. Department of Nephrology and Rheumatology
  2. Georg-August-University Göttingen
  3. Germany
  4. Department of Dermatology
  5. Georg-August-University Göttingen
  6. Germany
  7. Fresenius HemoCare Adsorber Technology GmbH
  8. St Wendel, Germany
  1. Dr B Berner, Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
  1. H-P LEINENBACH,
  2. M HEPPER
  1. Department of Nephrology and Rheumatology
  2. Georg-August-University Göttingen
  3. Germany
  4. Department of Dermatology
  5. Georg-August-University Göttingen
  6. Germany
  7. Fresenius HemoCare Adsorber Technology GmbH
  8. St Wendel, Germany
  1. Dr B Berner, Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany

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C1q is thought to play a crucial part in the pathogenesis of systemic lupus erythematosus (SLE).1-3 C1q deficiency and the presence of C1q autoantibodies are associated with increased disease activity in SLE.1 Therefore, C1q is a promising candidate for adsorption of pathogenetic relevant molecules from the plasma of patients with SLE. A C1q immunoadsorbent was developed in 19904 and has been used in several patients.5

Our patient, a 25 year old woman, had a relapsing malar and discoid rash, which extended to almost the whole integument, since January 1999. Accompanying oral and genital ulcers, polyarthritis, and lupus nephritis (histological membranous glomerulonephritis, WHO Va), as well as laboratory abnormalities, led to the diagnosis, SLE.6 Despite treatment with chloroquine (400 mg/day) initially and methotrexate (7.5–15 mg/week) since August 1999 in combination with prednisone (10 mg/day) no remission of the cutaneous lesions occurred. The dose of prednisone was repeatedly increased up to >60 mg/day. The lupus nephritis with a proteinuria of about 1.5 g/day and a non-active urine sediment remained unchanged, too. Continuing disease activity was also documented by abnormal serological parameters (table 1). Therefore, C1q immunoadsorption withMIRO adsorbers (Fresenius HemoCare) was started.

Table 1

 Serological parameters

Twelve C1q immunoadsorptions with an average treated plasma volume of 2 litres (equal to 34 ml/kg body weight) for each adsorption were carried out during a period of four weeks. The plasma volume was slightly reduced after the fourth session because of a fibrinogen decrease to <0.8 g/l. For plasma separation a centrifugal method in a closed continuous flow system was used. The veno-venous (both cubital venules were used) blood flow was about 50 ml/min and the plasma flow about 30–40 ml/min. The C1q immunoadsorption was well tolerated by the patient, and no side effects were noticed. The treatment with methotrexate (15 mg/week) and prednisone (10 mg/day) was continued. During C1q immunoadsorption a rapid and complete resolution of the malar and discoid rash was seen (fig 1), whereas the lupus nephritis with a proteinuria of about 1.5–2.0 g/day persisted. In addition, the pathological values of anti-dsDNA and C1q autoantibodies completely normalised and the circulating immune complexes (IgM) also declined (table 1).

Figure 1

Discoid rash of both femurs (ventral side) before C1q immunoadsorption (A). After 12 C1q immunoadsorptions the rash resolved completely (B).  

A follow up of 12 months after stopping the C1q immunoadsorption showed no relapse of cutaneous exacerbation or increase in clinical disease activity. Treatment with methotrexate (15 mg/week) and low dose prednisone (5 mg/day) was continued.

The C1q immunoadsorbents (MIROadsorbers) consist of polyacrylamide beads coated with covalently bound swine C1q. Effective clearance of circulating immune complexes as well as of C1q autoantibodies can be achieved.5 Moreover, additional molecules, such as fibrinogen, are bound by the collagen-like region of C1q.5 As fibrinogen decreased to <0.8 g/l in our patient during treatment, the plasma volume had to be slightly reduced. Other possible side effects, such as marked thrombocytopenia or anaphylactic reactions according to an increased bradykinine synthesis, were not seen. In contrast with the plasma exchange treatment, only selective plasma components are removed, and plasma replacement, for example by fresh frozen plasma, is not required. Therefore, the risk of transmitting infections by products derived from blood is minimised. With decreasing levels of circulating immune complexes and C1q autoantibodies the malar and discoid rash rapidly resolved in our patient. This observation emphasises the pathogenetic role of these molecules in SLE-specific cutaneous manifestations as an immune complex disease.7 However, the lupus nephritis was not improved, as indicated by an unchanged proteinuria. This may be because the lupus nephritis was not active. Therefore, proteinuria may be the result of chronic renal damage.

Used with other treatment, C1q immunoadsorption proved to be effective and safe. One might speculate that SLE-specific active cutaneous lesions, such as malar and discoid rash, may well respond to this immunoadsorption treatment. Because conventional plasma exchange treatment as an adjunct of standard treatment is restricted to only a few cases,8 the exact role of C1q adsorption within the multimodal treatment of SLE needs to be evaluated in controlled studies.

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