Comparison of double filtration plasmapheresis with immunoadsorption therapy in patients with anti-glomerular basement membrane nephritis.

BACKGROUND: Double filtration plasmapheresis (DFPP) and (IA) are both used to clear antibody. However, the clinical efficacy and safety of DFPP in patients with anti-glomerular basement membrane (anti-GBM) disease are unclear. METHODS: The 28 enrolled patients diagnosed serologically and pathologically with anti-GBM disease from 2003 to 2013 included 16 treated with DFPP and 12 with IA, with all patients administered immunosuppressive agents. DFPP consisted of an EC50W filter for plasma separation and an EC20W filter for plasma fractionation. A double volume of plasma was processed, and each patient received a 30-40 g human albumin supplement during each session. IA consisted of 10 cycles per session, with 8-10 sessions performed daily or every other day and each session regenerating 30-60 L of plasma. Serum anti-GBM antibodies and IgG were measured, and urinary and blood tests were performed, before and after each procedure. Renal function and outcome were determined. RESULTS: The 28 patients consisted of 13 males and 15 females, of median age 44.5 years (range, 22.5-57 years). Six patients had pulmonary hemorrhage and 18 had serum creatinine concentrations >500 umol/L. The average serum creatinine concentration at early onset of disease was 525 umol/L while the peak concentration was 813 umol/L. All patients showed progressive increases in serum creatinine and required CRRT during the course of disease. Pathological examination showed an average 73.9% of crescents (range, 54.6-95.4%).The clinical and pathological features of the DPPP and IA groups were similar. Efficacy of clearing anti-GBM antibody was similar in the two groups (59.0 vs. 71.2%, P = 1.00), although fewer patients in the DFPP group experienced reduced IgG (62.7 vs. 83.5%, p = 0.002). One patient each had a pulmonary hemorrhage and a subcutaneous hemorrhage during treatment, but there were no other serious complications. At the end of follow-up, patient survival and renal survival were similar in the DFPP and IA groups. CONCLUSION: DPPP plus immunosuppressive therapy efficiently and safely removed anti-GBM antibodies. The fewer plasma-associated side effects and reduced loss of IgG suggest that DFPP may be a better treatment choice for anti-GBM disease, especially in patients with insufficient plasma.

Exacerbation of experimental autoimmune encephalomyelitis by passive transfer of IgG antibodies from a multiple sclerosis patient responsive to immunoadsorption.

The pathogenic role of antibodies in multiple sclerosis (MS) is still controversial. We transferred to mice with experimental autoimmune encephalomyelitis (EAE), animal model of MS, IgG antibodies purified from a MS patient presenting a dramatic clinical improvement during relapse after selective IgG removal with immunoadsorption. Passive transfer of patient's IgG exacerbated motor paralysis and increased mouse central nervous system (CNS) inflammation and demyelination. Binding of patient's IgG was demonstrated in mouse CNS, with a diffuse staining of white matter oligodendrocytes. These data support a growing body of evidence that antibodies can play an important role in the pathobiology of MS.

[Effect of atoxil and triglobulin on cytokine balance and level of C-reactive protein upon treatment of children with serious forms of bacterial infections].

81 children with severe forms of the bacterial anginas passing on endotoxinemia of intestinal origin were examined. Use of preparations atoxil and triglobulin in a complex therapy was accompanied by normalization of cytokine activity and level of C-reactive protein on the background of reduction of concentration endotoxin in blood serum.

Immunoadsorption of alloantibodies onto erythroid membrane antigens encapsulated into polymeric microparticles.

PURPOSE: Classical immunoadsorbents used for the removal of deleterious molecules in blood such as auto-antibodies are prepared by covalent coupling of antigens onto previously chemically activated supports. Such a chemical treatment may induce a potential toxicity which can be reduced if new immunoadsorbents are prepared by encapsulating erythrocytes-ghosts carrying antigens inside polymeric and porous microparticles. MATERIALS AND METHODS: Erythrocyte-ghosts obtained by hemolysis in hypotonic buffer were encapsulated into ethylcellulose microparticles by w/o/w emulsification. The porosity of microparticles was evaluated by mercury porosimetry. The adsorption ability of encapsulated antigens was evaluated by hemagglutination after contact in tube or elution in column with polyclonal antibody solutions or human blood-plasma. RESULTS: The encapsulation process did not significantly alter the evaluated antigens since a significant decrease in anti-A (from 256 to 4) as well as anti-Kell (from 64 to 2) antibody titer has been observed in column after eight chromatographic runs (2 h). The higher the ghost concentration (total protein content of 6 mg/ml), the higher the adsorption capacity. CONCLUSION: Encapsulation, currently used for drug delivery purposes, may consequently also be applied to the design of new immunoadsorbents as biomaterials.

[Focal segmental glomerulosclerosis].

Focal segmental glomerulosclerosis (FSGS) is one of the major causes of nephrotic syndrome in adult as well as in the children. Untreated or steroid-resistant primary FSGS often shows a progressive renal insufficiency and reaches to end-stage renal failure. Concerning the treatment for such patients, the combined immunosuppressive therapy with corticosteroid and other cytotoxic drugs (cyclophosphamide, cyclosporine and tacrolimus etc.) is recommended. Since podocyte injury seems to be the most important primary events in FSGS, the extensive studies have been focused on the role of podocyte-related molecules. Recently slit membrane-associated molecules (CD2AP, alpha-actinin 4 and podocin) and angiotensin II type I receptor in the podocyte have been clearly shown to be relevant for the pathogenesis of FSGS.

Treatment of systemic lupus erythematosus by immunoadsorption in a patient suffering from tuberculosis.

We report on a 40-year-old man, admitted with fever and weight loss, in whom systemic lupus erythematosus (lupus nephritis World Health Organization type IV) and concomitant acute lung tuberculosis were diagnosed. Conventional treatment of diffuse proliferative nephritis with cytotoxic drugs was thought to be too dangerous in the presence of active tuberculosis. A combination of immunoadsorption and steroids was instituted for the treatment of systemic lupus erythematosus. Antibodies against double-stranded DNA decreased, and proteinuria decreased from 10 g/24 hours to less than 1 g/24 hours. Tuberculosis was treated initially with quadruple-drug therapy, then a triple-drug protocol. Primarily enlarged lymph nodes decreased to normal size after 3 months. The combined treatment modality of steroids and immunoadsorption was effective and safe, even in this patient with active tuberculosis.

A new DNA immune adsorbent for hemoperfusion in SLE therapy: a clinical trial.

This investigation studied the preparation and clinical trial of DNA immunoadsorbent for hemoperfusion in systemic lupus erythematosus (SLE) therapy. DNA was complexed with blue tetrazolium (BT), then mixed with collodion, and finally adsorbed on macroporous spherical polymeric adsorbent. The percentage of DNA thus immobilized was 98-98.5%, and no release was detected during hemoperfusion. A patient with severe SLE was treated with the above adsorbent in hemoperfusion. The patient was in coma, with high anti-DNA antibody and abnormal immune complex levels, which fell sharply from 56.34% to 0.8% after 2.5 h of whole-blood hemo perfusion. There were no major clinical complications, and 2 weeks later, her proteinuria level became normal and immune complex levels were sustained. She was then discharged from the hospital and has been in good health for more than 1 year.

Hemoperfusion based on artificial cells for aluminium and iron removal, immunosorption, fulminant hepatic failure, uremia, poisoning and metabolic assists.

The author reviewed artificial cells and their applications in hemoperfusion for chronic renal failure, poisoning, fulminant hepatic failure, removal of aluminium and iron, and metabolic assists. Other areas reviewed included artificial cells containing enzymes, multienzymes, immunosorbents, cell cultures and other areas. Artificial cells can be formed as membrane coated adsorbent or microencapsulated adsorbent, enzymes and cells. The large surface to volume relationship and the ultrathin membrane of artificial cells allows the rapid equilibration of metabolites. Artificial cells containing enzymes, ion exchange resin and activated charcoal have been used for hemoperfusion. The microencapsulated or membrane coated absorbents, enzymes, cells, immunosorbents and other material are prevented from releasing unwanted material into the circulation and prevented from adverse effects on blood cells. Because of the problem of charcoal in releasing emboli and depleting platelets we first developed coated activated charcoal hemoperfusion for clinical application. This has been used extensively in clinical studies. The artificial cell approach has also been applied to a number of other hemoperfusion approaches. The lack of space only allows this paper to summarize some of the approaches originated from this research centre.