静脉用免疫球蛋白在系统性红斑狼疮治疗中的应用

静脉用免疫球蛋白(IVIg)主要通过Fc受体介导免疫调节作用治疗系统性红斑狼疮(SLE),其他机制包括抑制补体介导的损伤,调控细胞因子的产生;调控独特型抗体网络,中和病理性自身抗体;调节B细胞和T细胞功能,下调抗体的产生等。IVIg已成功治疗SLE相关的顽固性血小板减少症、中枢神经系统狼疮、狼疮性肾炎及对传统免疫治疗无效或同时合并感染的SLE。     

Intravenous immunoglobulin therapy for diabetic amyotrophy

A 49-year-old woman with diabetes mellitus developed progressive weakness and atrophy of both thighs rendering her wheelchair-bound within two months. The neurological findings and electrophysiological test results were compatible with diabetic amyotrophy (DA). Immediately after intravenous immunoglobulin (IVIg) therapy (20 g x 3 days), she became able to walk with a cane. After the next course of the therapy, she could walk without assistance. This dramatic effect of IVIg therapy together with the recent observation of vasculitic neuropathy in DA indicates an inflammatory process in this condition, and gives support to this treatment for DA.     

Intravenous immunoglobulin therapy of antiphospholipid syndrome

OBJECTIVE: To review the role of intravenous immunoglobulin (IVIg) in antiphospholipid syndrome (APS). METHODS: A literature search was carried out for the immunopathogenesis of APS, laboratory evidence for the beneficial effect of IVIg in APS, and the clinical use of IVIg in APS. RESULTS: There is both laboratory and clinical evidence for the beneficial role of IVIg in APS. IVIg succeeded in in vitro inhibition of anticardiolipin antibodies and lupus anticoagulant, and in the amelioration of experimental APS. Although there are few case reports about IVIg therapy in the haematological manifestations of APS, most of the reports focus on the use of IVIg in the obstetric complications of APS. Hence, in several patient series the use of IVIg either solely or in combination with aspirin/heparin resulted in successful pregnancy outcome in the vast majority of APS patients with recurrent abortions. In addition, IVIg was also beneficial in antiphospholipid antibody-positive patients undergoing in vitro fertilization. CONCLUSION: APS, an autoimmune disease whose main features are vascular thrombosis and pregnancy morbidity, is a good candidate for immunotherapy with IVIg that contains anti-idiotypes directed towards patients' pathogenic antiphospholipid antibodies. Future research should determine when to use anticoagulation, IVIg or both in the treatment of APS.     

Intravenous immunoglobulin therapy: New aspects and outlook

Summary Experiences gathered while exploring the usefulness of intravenous immunoglobulin for children with idiopathic (immune) thrombocytopenic purpura (ITP) are reviewed in view of further investigations characterizing the effects of IgG i.v. in other immune diseases without detectable antibody deficiency. The most pertinent factors to be considered are i) the heterogeneity of an immune disease investigated; ii) the criteria used to evaluate the effects of the IgG therapy; iii) the IgG preparations used and i.v. dose-fractionation. Controlled, prospective clinical trials will be required to further explore the practical usefulness of IgG i.v.     

Intravenous immunoglobulin therapy in thrombocytopenic infectious mononucleosis

Severe haemorrhagic thrombocytopenia in infectious mononucleosis with positive Epstein-Barr virus (EBV) serology remains a threatening clinical problem. Although rare, fatalities have been reported. We present clinical, haematological and serological details of two patients with diffuse bleeding associated with this disease who failed conventional steroid treatment and who both responded promptly and effectively to infusions of intravenous immunoglobulin (i.v. Ig). A platelet immunofluorescence test was used to detect platelet antibodies in acute and recovery phase patient sera against autologous recovery platelets and against normal allogeneic group O platelets. In one patient, indirect immunofluorescence using recovery platelets detected an IgG platelet autoantibody with acute phase autologous serum. No platelet antibody was detected in the second patient. The data presented demonstrate that response to i.v. Ig is independent of serological detection of platelet autoantibodies. Therapy with i.v. Ig should be considered in any case of haemorrhagic thrombocytopenia associated with EBV infection shown to be refractory to steroid treatment.     

Intravenous immunoglobulin therapy for severe Clostridium difficile colitis

Background—Many individuals have serum antibodiesagainst Clostridium difficile toxins. Those with animpaired antitoxin response may be susceptible to recurrent, prolonged,or severe C difficile diarrhoea and colitis.
Aims—To examine whether treatment with intravenousimmunoglobulin might be effective in patients with severepseudomembranous colitis unresponsive to standard antimicrobial therapy.
Patients—Two patients with pseudomembranouscolitis not responding to metronidazole and vancomycin were givennormal pooled human immunoglobulin intravenously (200-300 mg/kg).
Methods—Antibodies against Cdifficile toxins were measured in nine immunoglobulinpreparations by ELISA and by cytotoxin neutralisation assay.
Results—Both patients responded quickly as shownby resolution of diarrhoea, abdominal tenderness, and distension. Allimmunoglobulin preparations tested contained IgG against Cdifficile toxins A and B by ELISA and neutralised the cytotoxicactivity of C difficile toxins in vitro at IgGconcentrations of 0.4-1.6 mg/ml.
Conclusion—Passive immunotherapy withintravenous immunoglobulin may be a useful addition to antibiotictherapy for severe, refractory C difficile colitis. IgGantitoxin is present in standard immunoglobulin preparations andC difficile toxin neutralising activity is evident at IgGconcentrations which are readily achieved in the serum by intravenousimmunoglobulin administration.

     

Intravenous immunoglobulin therapy in systemic lupus erythematosus-associated thrombocytopenia

Seven patients with thrombocytopenia and systemic lupus erythematosus were treated with intravenous (IV) doses of human immunoglobulin to assess clinical response and to examine the mechanism of action of IV immunoglobulin in these patients. Five of 7 patients had a greater than 50% increase in their platelet counts. Four of these patients had a sustained benefit of at least 6 months duration. The initial effectiveness of IV immunoglobulin therapy was not dependent on the reduction of levels of circulating platelet-binding IgG or circulating immune complexes.     

Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome

OBJECTIVE: To review the experience with intravenous immunoglobulin (IVIG) therapy in patients with Stevens-Johnson syndrome (SJS) in our institution. METHODS: All charts of patients with SJS admitted to Children's Hospital between November 1988 and June 1998 were reviewed. RESULTS: Twelve patients with SJS were detected. There were 8 males and 4 females, with a mean age 6 years (range 10 mo to 17 yrs). All patients presented with high fever and cutaneous and mucous membrane changes, and the diagnosis SJS was confirmed by a dermatologist. Of the 12 patients with SJS, 7 were treated with IVIG, 2 with corticosteroids, and 3 with supportive care. IVIG was administered in a single infusion at 1.5-2 g/kg, and was given on an average of hospital day 3 (range 1-8 days). The average duration of fever was 8 days (range 3-14) in the IVIG treated patients compared to 14 days (range 6-20) in the non-IVIG treated group (p = 0.06). The mean hospital stay was 12 days (range 4-22) for the patients treated with IVIG and 15 days (range 6-25) for the non-IVIG treated group (p = 0.5). No toxicity was observed with IVIG therapy. CONCLUSION: Duration of fever was shortened in patients treated with IVIG, although statistical significance was marginal. The hospital stay was slightly shortened in patients treated with IVIG; however, statistical significance was not reached. Prospective and controlled, multicenter studies are needed to further investigate these preliminary findings.     

Intravenous immunoglobulin therapy for juvenile dermatomyositis: efficacy and safety

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG) for the treatment of juvenile dermatomyositis (JDM) in patients who were unresponsive to corticosteroids (steroid resistant or steroid dependent) or showed unacceptable toxicity. METHODS: A retrospective chart review of the course of all patients with JDM treated with IVIG who attended the Dermatomyositis Clinic at The Hospital for Sick Children, Toronto, Canada, from August 1986 to December 1996. RESULTS: Eighteen patients with JDM were treated with IVIG. Ten patients were taking additional 2nd line treatments, methotrexate, azathioprine, cyclosporine, and cyclophosphamide. The main indication for starting IVIG was the failure of steroid therapy to induce remission of JDM. Twelve patients showed clinical improvement with IVIG. In these patients, the corticosteroid dose was reduced by > 50% for > 3 months without clinical or biochemical flare. Nine of these 12 patients had IVIG alone as a 2nd line agent, whereas 3 patients were treated with additional agents. Six patients remained steroid dependent; they subsequently required multiple agents to induce remission of JDM. CONCLUSION: Most steroid dependent or steroid resistant patients in our clinic were able to markedly reduce their dose of corticosteroid with the addition of IVIG. Given the retrospective nature of our data and the fact that multiple agents were sometimes used together, it will be important to confirm these findings in a controlled trial.     

Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis

The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations. Received: 14 January 2000 / Accepted: 20 March 2000     

Intravenous immunoglobulin therapy suppresses manifestations of the angioedema with hypereosinophilia syndrome

Angioedema with hypereosinophilia syndrome has a dramatic clinical presentation that may result from T-cell dysregulation and/or eosinophil dysfunction. Symptoms may be either episodic or persistent and are usually responsive to systemic glucocorticosteroid therapy. This diabetic patient had a dramatically severe presentation, responsive to high-dose steroids but relapsing when prednisone was tapered. To decrease his risks from long-term steroids, a therapeutic trial of intravenous immunoglobulin (IVIG) was tried, and a slow taper off of glucocorticosteroids achieved a prolonged remission. A brief recurrence and subsequent remission of eosinophilia and symptoms were associated with changes in the IVIG preparation lot and source. We conclude that some cases of angioedema with hypereosinophilia syndrome may be highly responsive to IVIG therapy and, furthermore, that specific sources and/or lots of IVIG may have significantly different immunoregulatory properties.     

Intravenous immunoglobulin for secondary immunodeficiency

Summary Viral and bacterial infections are a serious cause of morbidity and mortality in patients immunocompromised as a result of malignancy, burns, trauma, viral infections or chemotherapy. The development of safe and effective antibody preparations suitable for intravenous use have transformed the lives of patients suffering from forms of primary immunodeficiency characterised by antibody deficiency. However, the role of intravenous immunoglobulin (IV IgG) preparations in the treatment of secondary immunodeficiencies is less clear and although many anecdotal reports exist for the use of IV IgG in various secondary immunodeficiencies (Table 1), there have been few controlled trials of a sufficient size that have demonstrated clear-cut efficacy in many of the suggested new indications.     

Intravenous immunoglobulin therapy results in post-infusional hyperproteinemia,increased serum viscosity,and pseudohyponatremia

Intravenous immunoglobulin (IVIG) therapy is associated with rare reports of thromboembolic events and severe hyponatremia. We hypothesized that IVIG therapy may result in hyperproteinemia, increased serum viscosity, and pseudohyponatremia. We conducted a prospective observational study to evaluate the incidence of hyperproteinemia occurring after IVIG therapy and its relationship to serum sodium, viscosity, osmolality, and the serum osmolar gap. Eighteen IVIG infusions at a standard dose of 2 g/kg administered over 2-5 days were evaluated. Serum glucose, sodium, protein, viscosity, osmolality, and a calculated osmolar gap were obtained prior to therapy, 6 hr after the initiation of therapy, 24 hr after the conclusion of therapy, and on post-treatment day 10. Paired t-testing revealed a statistically significant increase in serum protein and viscosity and decrease in serum sodium and calculated osmolality 24 hr after the completion of IVIG therapy. The calculated serum osmolar gap increased insignificantly. In multivariate analysis, hyperproteinemia at the 6-hr time point predicted hyponatremia (P < 0.000), and hyperproteinemia at the 24-hr time point predicted both hyponatremia and increased serum viscosity (P = 0.024). These data demonstrate that increased serum viscosity occurs following IVIG therapy due to hyperproteinemia, and the rare hyponatremia reported is a pseudohyponatremia also due to hyperproteinemia.     

Intravenous immunoglobulin as adjunctive therapy in kidney transplant recipients with severe pneumocystis pneumonia

Pneumocystis jirovecii is an opportunistic pathogen that may cause severe, life‐threatening respiratory infections in immunocompromised patients such as those with kidney transplants. Although antimicrobial prophylaxis is now universally recommended in the early post‐transplant period, Pneumocystis pneumonia (PCP) can occur later. If such infection occurs, mortality rates are high. Beyond standard therapy with trimethoprim‐sulfamethoxazole, there is a lack of evidence‐based options for intensifying treatment when initial therapy fails to show improvement. Moreover, it is usual to minimize immunosuppression in life‐threatening infection, but graft damage may occur, particularly in kidney transplant recipients at above‐average immunological risk. Here we present two cases of severe PCP in high immunological risk recipients who were managed with adjunctive intravenous immunoglobulin and withdrawal of immunosuppression. Both patients recovered and were discharged from hospital with functioning grafts.