Complications of plasma exchange in patients with neurological diseases

Summary Plasma exchange has proven to be effective in diseases of established or presumed autoimmune etiology as well as in hyperviscosity syndromes and some rare metabolic disorders. Its application is thought to be relatively safe; nevertheless, severe complications may occur. We therefore analyzed the complications of 291 exchanges in 39 patients with neurological diseases. Minor complications developed in 4.8% and major complications in 2.7% of procedures, including one death. Severe infections and technical problems have been the most serious side effects, sometimes followed by organ failure or even death.Abbreviations ARDS adult respiratory distress syndrome - FFP fresh frozen plasma - GBS Guillain-Barré syndrome - LDL low density lipoproteins - MS multiple sclerosis - MG myasthenia gravis - PNP polyneuropathy     

Complement-mediated inhibition of immune precipitation in patients with immune complex diseases

The ability of human sera to prevent the precipitation of antigen-antibody complexes has been investigated. The early complement components including C3 are required for optimal prevention of immune precipitation, whereas the later components are not required. The sera of 36 of 75 patients with seropositive rheumatoid arthritis (RA), 14 of 32 with SLE and four of 17 with glomerulonephritis exhibited reduced capacities to prevent immune precipitation. In contrast sera from patients with seronegative RA, ankylosing spondylitis, psoriatic arthritis or degenerative joint disease were normal in this respect. In SLE and GN sera hypocomplementaemia was frequently associated but not always with failure to prevent immune precipitation, whereas only a small proportion of the patients with seropositive RA and reduced capacity to retain complexes in a soluble form were hypocomplementaemic. Thus the failure of sera to prevent the precipitation of antigen-antibody complexes is not always associated with hypocomplementaemia.     

血浆物质对红细胞免疫粘附功能的调节作用

目的探讨不同分子量血浆物质的浓度改变对红细胞免疫粘附功能的影响。方法利用柱层析法分离血浆不同分子量物质，通过建立血浆物质浓度梯度红细胞酵母菌花环率的方法，观察血浆物质浓度对调节红细胞免疫粘附功能的作用。结果１．随血浆、大分子量血浆物质浓度增高，红细胞Ｃ３ｂ受体酵母菌花环率（ＲＢＣＣ３ｂＲＲ）先增高而后降低；２．中小分子量血浆物质则随浓度升高ＲＢＣＣ３ｂＲＲ升高；３．血浆、中小分子量血浆物质５８℃、３０分钟灭活后ＲＢＣＣ３ｂＲＲ较灭活前显著增高，而大分子量血浆物质灭活前后ＲＢＣＣ３ｂＲＲ无显著改变。结论大分子量血浆物质对红细胞免疫粘附功能具有双向调节作用；中小分子量血浆物质能增强红细胞免疫粘附功能。推测某些大分子物质能激活ＣＲ１，中小分子量血浆物质中Ｃ３ｂ片段和Ｃ３ｂ灭活因子（ＫＡＦ）在调节红细胞免疫粘附功能中起着重要作用。     

Altered monocyte function in patients with benign breast disease.

Monocyte migration, lysozyme production and phagocytosis was studied in 34 patients with fibroadenosis, 28 patients with fibroadenoma and 48 healthy female controls. In patients with fibroadenosis and fibroadenoma, monocyte migration and phagocytic activity were significantly reduced when compared to controls (P less than 0.001). Conversely, lysozyme production by monocytes from patients with benign breast disease was significantly higher than in controls (P less than 0.001). In 20 patients with benign breast disease, there was no significant difference in monocyte function before and 3 months after operation. The observed impairment of monocyte function in fibroadenosis and fibroadenoma would not appear to be the result of abnormal blood biochemistry or due to a direct serum inhibitor, but is probably related to an intrinsic cellular defect. Further studies are required to evaluate the significance of impaired monocyte function in the pathophysiology of benign breast disease.     

Plasmapheresis in patients with leukaemia, multiple myeloma and immune complex diseases

Therapeutical partial plasma exchange was performed on 9 patients with acute leukaemia, 14 patients with monoclonal and polyclonal gammopathies and 3 with primarily immune complex disease. The procedure was effective in 21 out of the 27 courses performed on patients with gammopathies and in all cases of the primarily immune complex diseases. In acute leukaemic patients the course of the disease was favourably influenced by plasmapheresis. The results show that partial plasma exchange is an effective adjunct therapy in the treatment of patients with haematological diseases.     

Influence of naturally occurring human immune complexes on monocyte movement in vitro

The influence of naturally occurring immune complexes (IC) on monocyte motility has been investigated. Both chemokinesis and chemotaxis have been measured, using modified Boyden chambers, in response to sera containing IC and to the same sera depleted of IC with 2% polyethylene glycol. Chemokinetic activity was markedly increased in the presence of IC-containing sera, and this increased activity was largely abolished, following IC depletion. The chemotactic activity of the IC-containing sera was largely independent of the IC content, since IC depletion only resulted in a modest decrease in stimulated movement. The chemotactic response to a standard chemoattractant (zymosan-treated sera) was significantly increased with the cells in the presence of IC-containing sera, and this effect was abolished following IC depletion. There was no relationship between the total IC concentration and changes in monocyte movement. These results indicate that circulating IC may markedly alter monocyte locomotion in such a way that more cells may be attracted more rapidly to an inflammatory focus.     

Defective monocyte function in patients with systemic lupus erythematosus

Peripheral blood adherent cells from patients with systemic lupus erythematosus (SLE) were shown to have markedly reduced phagocytic activity as compared to normal adherent cells or those from non-SLE patients receiving corticosteroid therapy. Both resting and phagocytosing monocytes showed decreased hexose monophosphate shunt and glycolytic activity. Mononuclear cells from SLE patients showed grossly impaired proliferative activity after NaIO4 activation. Furthermore, addition of SLE adherent cells to normal adherent cell-depleted lymphocytes decreased [3H]thymidine incorporation of the latter cells following NaIO4 treatment. Addition of normal adherent cells to SLE lymphocytes corrected the previous defect, indicating that an adherent abnormality is responsible for the defect in SLE mononuclear cell proliferation to NaIO4 activation.     

The effect of protamine sulfate on the course of immune complex glomerulonephritis in the rat.

In vivo studies in rats demonstrated that the binding of a highly cationic antigen (cationized human IgG, pI greater than 9.5) to glomerular polyanion could be significantly reduced by prior application of a small polycation, protamine sulfate. The degree of inhibition was dose dependent and the highest dose used, 4 mg/100 g body weight, reduced antigen binding by approximately 70%. In further experiments the ability of protamine sulfate to enhance elimination of cationic antigen-antibody immune complexes from the glomerular capillary wall was examined. Daily treatment with protamine sulfate, starting after induction of nephritis, produced a significant but only moderate reduction in the persistence of the antigen, without having any effect on proteinuria. Proteinuria could only be prevented when protamine sulfate was given immediately before induction of nephritis. Protamine sulfate had little influence on the course of established renal disease in the model employed. These results do not substantiate the concept of charge competition as a potentially useful therapeutic strategy.     

The effect of disgust on oral immune function

Disgust motivates avoidance of pathogen sources, but whether its role in disease avoidance extends into activating the immune system is unexplored. This was tested here by comparing oral immune markers before and after a disgust induction, relative to neutral and negative induction control groups. The disgust group, but not controls, revealed an oral inflammatory response, with increased salivary tumor necrotizing factor alpha and albumin, as well as a down-regulation of immunoglobulin A (SIgA) secretion. It has been hypothesized that disgust evolved in animals to clear toxins from the oral cavity by gaping and increased salivary flow. Our data suggest down-regulated SIgA secretion may be a vestige of this response so as to conserve protein, while the inflammatory reaction may reflect an adaptive response to disease threat, selectively triggered by disgust. The broader implications of these data for a discrete neuro-gut-immune axis are examined.     

The effect of plasma upon lymphocyte response in vitro. Demonstration of a humoral inhibitor in patients with sarcoidosis

The role of humoral inhibitors of lymphocyte functions was evaluated in subjects with sarcoidosis. A reproducible system was developed to evaluate the capacity of human plasma samples to support lymphocyte responses in vitro to PHA and to Candida albicans antigen.     

Assessment of the combined effect of plasma exchange and plasma perfusion on patients with severe hepatitis awaiting orthotopic liver transplantation

To determine if plasma exchange combined with plasma perfusion is a reliable and effective temporary liver support treatment for patients on the waiting list for OLT, we tested this method in 5 patients with end-stage and 3 patients with middle-stage severe hepatitis. Four patients were successfully controlled until a donor liver was available 4 to 13 days later. In contrast, the remaining 4 patients were not adequately controlled by this treatment and experienced aggravated disease progression, dying 3 to 8 days after treatment while still awaiting OLT. Of those 4 patients who received OLT, 2 patients died from multi-organ failure caused by hepatic failure, while the other 2 survived. These findings show that plasma exchange combined with plasma perfusion provides temporary support for some patients on the waiting list for OLT. The ability of patients to successfully bridge to OLT is closely associated with the degree of liver failure, complications, multi-organ failure, and the length of the waiting period for a donor liver.     

The effects of various drugs and immune complexes on the function of alveolar macrophages from patients with collagen-vascular diseases with interstitial pneumonia

Alveolar macrophages (AM) taken from sixteen patients with collagen-vascular diseases with interstitial pneumonia (CVD-IP+) were cultured with prednisolone (PSL), prostaglandin E2 (PGE2), colchicine (Colch), D-penicillamine or aggregated IgG (agg-IgG). The culture supernatants were tested on the fibroblast proliferation function and the amounts of fibronectin (Fn) and interleukin 1 (IL-1). The fibroblast proliferation was suppressed significantly by the supernatants of AM cultured with PGE2. The Fn production by AM was significantly suppressed by PGE2 and Colch. The IL-1 production by AM was not suppressed by these drugs, but was enhanced by Colch. In five patients with CVD-IP+, the fibroblast proliferation of AM supernatant was enhanced by agg-IgG. In these five patients, Fn and IL-1 production had a tendency to be increased by agg-IgG. The ratio of immune complexes (IC) in broncho alveolar lavage fluids to those in sera was significantly higher in patients with CVD-IP+ than in patients with CVD without IP suggesting a local production of IC in the lung in the patients with CVD-IP+.     

Cascade filtration: clinical application in 26 patients with immune complex and IgM mediated diseases

A new technique which allows lymphocytapheresis to be combined with cascade filtration (CF) is described in this paper. This therapeutical approach was applied for the treatment of patients affected by necrotizing vasculitis (1), inflammatory myopathies (5), Cryoglobulinemia (5), immune complex polyneuropathies (7), rheumatoid arthritis (3) and psoriasis (3 patients). Two cases of Waldenstrom's macroglobulinemia were also treated after the onset of the hyperviscosity syndrome. 78 procedures have been performed without any untoward effect. From a clinical point of view all patients had some improvement following treatment, thereby confirming not only the clinical safety of this therapeutical approach but also its effectiveness at least in the management of diseases which usually respond to plasma exchange treatment. Laboratory investigations showed that with CF it is possible to selectively remove IgM, immune complexes, fibrinogen, lipoproteins and high molecular weight plasma components, sparing most albumin and IgG globulins (85 and 71%, respectively).     

β—内啡肽对大鼠免疫功能的影响

离体条件下,β-内啡肽(β-END)在10~(-6)-10~(-14)mol/L 可明显地促进ConA 诱导的脾淋巴细胞的转化及IL-2的产生,增加LPS 激活的腹腔巨噬细胞产生IL-1.纳络甯可阻断β-END 的这种作用.静脉注射β-END 也可增强大鼠脾淋巴细胞转化,促进IL-1和IL-2的产生.本结果提示,β-END 具有增强大鼠免疫功能的作用,这种作用可能是由阿片受体介导的。     

病毒性心肌炎患者外周血单核细胞来源树突状细胞的功能探讨

目的 探讨病毒性心肌炎患者外周血单核细胞来源树突状细胞(DCs)的功能,为治疗病毒性心肌炎提供一种新的途径.方法 选取病毒性心肌炎患者与身体健康、状态良好的志愿者各20例分别作为病例组与对照组,采集研究对象外周血单核细胞进行无菌化分离,再分别给予粒细胞巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)诱导外周血Mo-DCs,观察其表面形状变化、吞噬能力的变化以及其表达细胞因子的结果.结果 病例组外周血单核细胞Mo-DCs中的CD80、CD83、CD86及MHC Ⅱ表达水平高于对照组,但Mo-DCs吞噬功能低于对照组.与对照组比较,病例组患者细胞TNF-a较高(P＜0.05)和IL-12(P＜ 0.05).结论 病毒性心肌炎患者外周血单核细胞Mo-DCs处于一个十分成熟稳定的功能状态,可表达较高水平的IL-12和TNF-12.     

Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange.

By studying the clearance of autologous labeled antibody-coated or heat-damaged erythrocytes, we showed that reversible blockade of the splenic component of reticuloendothelial function existed in 14 of 15 patients referred for treatment of nephritis or vasculitis. In 10 patients treated by plasma exchange--alone in three and combined with steroids and cytotoxic drugs in six--reversal of splenic blockade followed in nine, and in the three patients treated solely by plasma exchange this reversal was demonstrated to occur within 48 hours of the procedure. Only gradual reversal of splenic blockade was found in three of five patients treated by steroids with or without cytotoxic drugs; no change in splenic function was observed in two. When circulating immune complexes were detected by a C1q-binding assay, there was, in serial studies, an approximate inverse correlation between splenic function and the level of C1q-binding material, though hyposplenism was also a feature of patients in whom the C1q-binding assay was negative.