Matthias Schneider
Division of Rheumatology, Medical Clinic and Policlinic, Heinrich-Heine-University
Düsseldorf; FRG
Systemic lupus erythematosus (SLE) is the most common systemic
connective tissue disease with a very heterogenous expression.
During the last 2 decades, prognosis has generally improved due
to more sensitive diagnostic testing and new opportunities in
immunosuppressive therapy. Although about 80 % of the patients
survive for at least 10 years, there are still some patients with
severe disease activity needing additional therapeutic options.
In addition, late morbidity and mortality raise some questions
concerning our therapy strategies.
Since first description, numerous studies have been published
documenting the benefit of plasmapheresis in acute severe lupus.
Although controlled trials failed to confirm a general indication
for plasmapheresis in SLE, there is still a rationale for attempting
extracorporeal methods in SLE, the prototype of human diseases
that are mediated principally by immune complexes (IC). Analysis
of plasmapheresis has shown that plasma exchange acts by clearing
the reticuloendothelial system and by removing autoantibodies,
mediators of inflammation and circulating IC.
Extracorporeal therapies are safe treatments; only 3 % of patients
treated with plasmapheresis will develop complications.
In recent years, efforts have been made to develop more specific
extracorporeal techniques to remove the pathogenic substances
from the plasma. Immunoadsorbent columns with polyvinyl alcohol
gel immobilized by phenylalanine (IM-PH - 350) or tryptophan as
ligands bind IC by hydrophobic interactions.
51 patients (mean age: 31.9 +/- 6.5 y) with a mean disease duration of 4.2 years, who met 4 or more of the revised criteria for the classification of SLE, were included in this study. Indications for immunoadsorption were given by an increase in disease activity. Immunadsorption was performed by separating plasma by centrifugation. 2.5 liters of plasma were perfused at each immunoadsorption, and 3 perfusions were undertaken on each patient over a period of 7 days. The perfused plasma was then reinfused together with the separated blood cells. In 46 patients, IMPH - 350 (DIAMED, Cologne) was used as adsorber, in 5 lg-Therasorb with sheep anti-human immunoglobulin antibodies coupled to Sepharose CL-4B (Baxter, Munich).
We document a clinical response in 39 out of 50 SLE patients treated
with immunoadsorption. An improvement was reached in patients
with defined disease activation without any important side effect.
In most patients, this response was preserved for up to 6 months.
Our results underline that IMPH - 350, a column with a capacity
limited to 2.5 liters plasma, is of additional benefit to immunosuppression
in most indications used in our investigation. Best results were
found in CNS involvement, hemocytopenias, common disease activity
and vasculitis. In these patients, immunoadsorption prevented
a change in immunosuppressive therapy to a drug with higher risk
for side effects.
Our results in patients with lupus nephritis indicate also that
the time of organ manifestation is one important aspect for focusing
the window of indications for extracorporeal therapy on SLE and
probably other autoimmune diseases. 4 out of 5 patients with lupus
nephritis of less than 12 months improved, against only 2 out
of 6 with a longer lasting kidney involvement. The same will be
expected in CNS involvement for example, where all patients but
one had their CNS related symptoms less than 6 months. Late use
of extracorporeal therapies may only be helpful with continuously
replicating cells as target, e.g. thrombocytes, but will not prevent
chronic damage if non-replicating cells like glomeruli are the
goal. But the early use of extracorporeal therapy in lupus nephritis
is a useful adjunct to immunosuppressive drugs.
The first SLE patients treated with the Ig-Therasorb columns showed
clinical response using a procedure adapted from the IMPH - 350.
No columnspecific side effects could be observed; because of the
selectivity for immunoglobulins no replacement fluid or substitution
was required. By perfusion of 2.5 liters plasma, ds-DNA antibody
titer was reduced by about 40 % after the first and by 50 - 60
% after the third treatment. IgG was reduced in comparable amounts
to anti-ds-DNA AB; IgM and IgA decrease was about half value.
Despite its relative non-specificity, the possible nearly complete
removal of IgG and the certainty of eliminating all circulating
pathogenic antibodies offer new opportunities in the therapy of
autoimmune diseases. One advantage of this new column may be the
continuous reduction of IgG-AB down to a defined limit. Other
possible applications are given by regenerating and recycling
of the column for one patient.
E. L. E. F.
European Lupus Erythematosus Federation