5th Tübinger Glomerulonephritis Workshop:

SLE and Lupus-Nephritis

T. Witte, R.E. Schmidt: Pathophysiology and immunology of SLE

(Nieren Hochdruckkrh 1995 (24) 666 - 667). The cause of SLE is unclear. Twin studies showed a genetical influence on the pathogenesis of the disease. Rare defects of several complement components leading ton a prolonged clearance of immune complexes can cause SLE-like syndromes. Fcgamma receptors, that also participate in the clearance of immune complexes, may play a role in the pathogenesis of SLE. The rate of CD32-"high responders" is increased among SLE patients. The Fcgamma receptor III (CD16) is expressed on activated mesangial cells of the kidney. It mediates release of cytokines after binding of immune complexes and may therefore participate to the pathogenesis of lupus nephritis. A recently published family study on the pathogenesis of lupus could mark HLA-B7-DR2 and HLA-B8-DR3 as risk haplotypes, however, no "SLE gene" was defined.
Keywords: SLE - lupus - pathogenesis - Fc receptors.

J. G. Saal, S. Koch, F.P. Fischer: Joint, tendon and bone manifestations of systemic lupus erythematosus

(Nieren Hochdruckkrh 1995 (24) 668 - 671). Involvement of joints in systemic lupus erythematosus (SLE) is one of the earliest and most frequent manifestations of the disease. This has been shown by retrospective analysis of 71 consecutive SLE patients at our institution where 61 % or 78 % of the patients presented with arthritis at onset or during the course of the disease. respectively. These figures correspond quite well with similar studies reported in the literature.
Keywords: SLE - involvement of joints.

W. Habscheid: The antiphospholipid syndrome

(Nieren Hochdruckkrh 1995 (24) 672 - 677). Antiphospholipid antibodies can be detected in laboratory by measurement of lupus anticoagulant and anticardiolipin antibodies. The linkage between antiphospholipid antibodies and vascular thrombosis, thrombocytopenia and recurrent fetal loss in patients with lupus erythematosus (SLE) is known since long time ago. In the last years this connection has been detected in patients without SLE too and the term of antiphospholipid syndrome (APS) was coined. Thrombosis of small and large vessels of hitherto not completely understood aetiology is essential in the pathogenesis of the clinical symptoms. Next to the classic symptoms a spectrum of additional clinical manifestations can be found whose presentation are determined by the character of thrombotic occlusions of vessel beds in different organs. Involvement of the kidneys in PS is possible but seldom critical in the clinical course. Beside thrombosis of the great organ arteries and veins, microscopic thrombotic microangiopathy is typical in renal histology. By measuring antiphospholipid antibodies in patients with SLE a group of persons with increased risk of venous and arterial thrombosis, cerebral complications, recurrent fetal loss and thrombocytopenia can be discerned. Because APS exist without SLE it should also be considered in non-SLE patients when classical symptoms, especially recurrent thrombosis of unknown aetiology, are present.
Keywords: antiphospholipid antibodies - lupus anticoagulant anticardiolipin antibodies - thrombosis - thrombocytopenia - recurrent fetal loss.

R. Fünfstück, P. Oelzner, T. Eidner, G. Stein: Epidemiology and clinical aspects of lupus nephritis

(Nieren Hochdruckkrh 1995 (24) 678 - 682). Lupus erythematosus is regarded as a typical autoimmune disease characterized by the involvement of a variety of organ systems. The disease is spread all over the world. An average prevalence of 20 - 50 cases and an incidence of 5 - 7 cases per 100.000 inhabitants must be taken into consideration. The prognosis of systemic lupus erythematosus is decisively influenced by its renal manifestation. In 35 to 75% of all cases, the kidneys are involved in the disease process. At present, no typical clinical or laboratory-chemical findings early indicating renal involvement as well as degree and severity of nephritis can be defined. Kidney biopsy is still of substantial importance for the diagnosis of the disease.
Keywords: systemic lupus erythematosus - nephritis - epidemiology.

I. Zäuner, E. Röther, P. Schollmeyer: Systemic lupus erythematosus and pregnancy

(Nieren Hochdruckkrh 1995 (24) 683 - 685). Systemic Lupus erythematosus (SLE) is an autoimmune disease, that primarily affects women of childbearing age. Worsening of SLE is uncommon during pregnancy. The course of the pregnancy depends on activity of the disease at time of conception. There should be evidence that the systemic disease is in complete remission for at least 6 months or more. A prophylactic therapy with prednisone in pregnant patients with SLE is not justified. When SLE is exacerbating, immunosuppressive therapy with prednisone or if needed in combination with azathioprine should be administered. For high titers of antiphospholipid antibody a treatment with low-dose acetylsalicylic acid or in case of previous spontaneous thrombosis, a combination therapy with heparin are recommended. Active SLE nephritis represents a relative or even absolute contraindication, depending on the clinical course. For monitoring the activity of the disease repeated determinations of complement proteins CH50, C3, C4 and C3d are helpful.
Keywords: systemic lupus erythematosus - pregnancy - antiphospholipid antibody - lupus nephritis.

H. H. Euler, J. O. Schroeder: Immunosuppressive treatment of systemic lupus erythematosus

(Nieren Hochdruckkrh 1995 (24) 686 - 696). Immunosuppression in SLE must be adjusted to the current level of disease activity. The spectrum of established treatment principles ranges from no treatment or non-steroidal antirheumatic drugs alone, to glucocorticoids, hydroxychloroquine, azathioprine and, finally, cyclophosphamide (Ctx). Repeated pulses of intravenous Ctx can be regarded today as established treatment for severe SLE manifestations. Administered in combination with prior plasmapheresis, pulse Ctx has led to long-term treatment-free remission in some patients. Additional treatment options, whose potential benefits remain to be defined, are cyclosporine A, methotrexate, highdose intravenous immunoglobulins and immunoadsorption. Possibly, high dose chemotherapy with autologous stem cell rescue might become a future treatment option. This review describes present knowledge regarding immunosuppression in SLE, especially the differentiated application of Ctx in severe SLE, and discusses the prospects for future development.
Keywords: systemic lupus erythematosus - treatment - corticosteroids - hydroxychloroquine - cyclophosphamide - plasmapheresis review.

Ch. Mrowka, H.-G. Sieberth: Cyclosporin A (CyA) in the treatment of systemic lupus erythematosus - a therapeutic alternative

(Nieren Hochdruckkrh 1995 (24) 697 - 701)? Morbidity and mortality of SLE are very much dependent of the course of the lupus nephritis. Though progression to chronic renal failure has become rare disease progression can often not be stopped by aggressive immunosuppressive therapy. CyA seems to be a new alternative in the treatment of lupus nephritis with nephrotic syndrome as it reduces proteinuria very rapidly. However, the lack of long-term studies, conflicting results concerning the effectiveness in down-regulating auto-antibody production, multiple side effects of CyA and disease relapses after the end of therapy have increased the skepticism towards CyA therapy in SLE. Further studies are necessary to evaluate the usefulness of CyA as an alternative therapy regimen in otherwise intractable SLE.
Keywords: cyclosporin A - systemic lupus erythematosus - lupus nephritis.

N. Braun: Plasma exchange and related procedures in the treatment of systemic lupus erythematosus

(Nieren Hochdruckkrh 1995 (24) 702 - 706). Plasmapheresis (plasma separation) is a generally acknowledged treatment for removing circulating injurious antibodies and other factors, i.e. immune complexes. For this particular reason, plasmapheresis was applied to patients with systemic lupus erythematosus (SLE) with conflicting results in the past. Controlled clinical trials demonstrated no benefit of concurrent plasmapheresis compared to conventional immunosuppressive therapy. Up to date, it is not clear whether plasmapheresis combined with a subsequent cytotoxic therapy in form of the synchronization protocol is more effective. Immunoadsorption to protein A is a better and safer treatment modality than plasmapheresis for the removal of disease-mediating auto-antibodies and immune complexes. Although clinical studies with greater numbers of patients are pending, this extracorporeal method is an important new therapeutic approach for therapy-resistant lupus.
Keywords: systemic lupus erythematosus - plasmapheresis - therapy - immunoadsorption - protein-A.