Combination Of Intravenous Immunoglobulin Research Articles

Treatment of neurodegenerative CNS disease in Langerhans cell histiocytosis with a combination of intravenous immunoglobulin and chemotherapy

In rare cases, patients with Langerhans cell histiocytosis (LCH) develop neurodegenerative CNS disease (ND-CNS-LCH). Management of ND-CNS-LCH has not been established. We treated five pediatric patients with a combination of intravenous immunoglobulin (IVIG) and chemotherapy (steroid +/- vinblastine +/- 6-mercaptopurine +/- methotrexate). Prior to the therapy, three of the five patients had cerebellar ataxia while the remaining two had abnormal MRI findings without apparent neurological deficits. IVIG was given monthly or twice monthly at the dosage of 250-400 mg/kg/dose. The four patients administered more than 23 doses of IVIG and chemotherapy remained in a stable condition and did not show significant progression signs in neurological deficits or brain MRI findings during the 30-month follow-up period (median; range: 19+ to 38+) following the initiation of therapy for ND-CNS-LCH. The IVIG-containing treatment may be promising for ND-CNS-LCH; however, its effectiveness remains to be further tested in more patients as well as in a randomized trial.

Desensitization strategies enabling successful renal transplantation in highly sensitized patients

Currently, the number of highly sensitized patients awaiting a renal transplant is increasing on the waiting lists of different organ exchange organizations. Due to the presence of antibodies against a broad variety of human leukocyte antigen (HLA) specificities, highly sensitized patients have a markedly reduced chance of receiving a crossmatch-negative organ. It has long been recognized that hyperacute rejection is associated with the presence of donor-specific anti-HLA antibodies at the time of transplantation. Meanwhile treatment protocols have been developed to achieve successful transplantation across antibody barriers. Therefore, the presence of donor-specific anti-HLA antibodies and a positive serological crossmatch are no longer considered as an absolute contraindication to renal transplantation. Mainly, two desensitization protocols have been established in order to overcome a positive crossmatch or to enhance the chance of highly sensitized patients to receive a crossmatch-negative organ: high-dose intravenous immunoglobulin (IVIg) or low-dose IVIg in combination with plasmapheresis. Herein, we summarize the characteristics of these two treatment regimes along with other alternative approaches that are currently used for the management of kidney graft recipients with broad alloantibody reactivity against potential kidney donors.

Effects of intravenous immunoglobulin and methylprednisolone on human umbilical vein endothelial cells in vitro

Endothelial cells (ECs) do more than just play a role in distinguishing blood and tissues. These cells are also influenced by various chemical mediators present in the blood and tissues. In addition, they produce diverse cytokines, chemokines, adhesion molecules, and growth factors. Therefore, ECs are actively involved in the inflammatory and immune response. We investigated the effects of intravenous immunoglobulin (IVIG) and methylprednisolone (MP) on activated human ECs, by examining the individual and combined effects of the drugs. Human umbilical vein ECs (HUVECs) obtained from the umbilical cords of healthy newborns were cultured. After the HUVECs were treated with interleukin (IL)-1 β, the effects of IVIG and/or MP on the activated HUVECs were assessed by cell proliferation, mRNA expression, and the production of vascular cell adhesion molecule (VCAM)-1, IL-1 β, and vascular EC growth factor (VEGF). IVIG and MP inhibited HUVEC proliferation. IVIG and MP significantly down regulated mRNA expression and the production of VCAM-1, IL-1 β, and VEGF. The combination of IVIG and MP generally showed a greater suppressive effect on mRNA expression and on the production of VCAM-1, IL-1 β, and VEGF. Our results suggest that some of the corticosteroid-sparing effects of IVIG observed in patients with severe asthma could be related to a decreased ability of ECs to proliferate, and to a down regulation of the expression of molecules involved in the onset and progression of airway inflammation.

Wegener's granulomatosis: clinical and laboratory results of a university hospital study of 20 patients from Turkey

The aim of this study was to evaluate the clinical and laboratory features, the treatment approaches, and the long-term outcome of patients with Wegener's granulomatosis (WG) who were followed up in our hospital. The hospital files of the patients with the diagnosis of WG who were followed up between the years 1985 and 2003 in Hacettepe University Hospital were retrospectively evaluated. Male/female ratio was 12:8. The mean age was 39 years (range 20-65 years). Constitutional symptoms and upper and lower airway involvement were seen in 95% of all patients. Renal and musculoskeletal symptoms were seen in 90 and 80% of the patients, respectively. Five patients were treated with oral monotherapy (three with methylprednisolone and two with cyclophosphamide). Three patients were given a combination of orally administered cyclophosphamide and methylprednisolone. Ten patients were treated with pulse cyclophosphamide and methylprednisolone combination together with oral alternate-day methylprednisolone therapy. The remaining two resistant patients were treated with pulse cyclophosphamide, methylprednisolone, and intravenous immunoglobulin combination together with oral alternate-day methylprednisolone. Four patients died because of the disease activity. Intravenous pulse therapies with oral, alternate-day methylprednisolone were well tolerated. Sixteen patients experienced long-term remission after immunosuppressive treatment. Eleven patients have been asymptomatic for more than 12 months. In five patients, residual symptoms persisted: constitutional symptoms and renal and respiratory tract symptoms in varying combinations. The demographic and laboratory findings in this trial were similar with those of the previous results. Alternate-day glucocorticoids plus cyctotoxic drugs may be beneficial in patients with WG.

Intravenous Immunoglobulin and Plasmapheresis in Acute Humoral Rejection: Experience in Renal Allograft Transplantation

Acute humoral rejection (AHR) in kidney transplantation is associated with higher rates of allograft loss when compared with acute cellular rejection (ACR). Treatment with intravenous immunoglobulin (IVIG) combined with plasmapheresis (PP) has been used recently in many centers. We report the incidence, clinical characteristics, and outcome of patients with AHR treated with IVIG and PP. All patients ( n = 519) at our institution who underwent kidney transplantation between January 1999 and August 2003 were retrospectively analyzed and classified according to biopsy results into three groups: AHR, ACR, and no rejection. AHR was diagnosed in 23 patients (4.5%) and ACR in 75 patients (15%). Mean follow-up was 844 ± 23 days. Female sex, black race, and high panel-reactive antibody were risk factors for AHR. Most AHR patients (22 of 23) were treated with IVIG and PP. Two-year graft survival was numerically worse in patients with AHR versus ACR (78% vs. 85%, p = 0.5) but the difference was not statistically significant. Graft survival after AHR treated with IVIG and PP is much better than it has been historically. IVIG in combination with PP is an effective treatment for AHR. Graft survival in this setting is similar to graft survival in patients with ACR.

Nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcysteine

We describe a case of an HIV-seropositive patient presenting with a severe stomatitis that initially improved with anti-infective agents. Only 13 days after the onset of the stomatitis, the patient developed rapidly progressive constitutional symptoms and a cutaneous eruption. He was diagnosed with a Stevens–Johnson syndrome (SJS) caused by the antiretroviral drug nevirapine (NVP). Despite meticulous supportive care and withdrawal of all drugs, his situation worsened and developed into a toxic epidermal necrolysis (TEN), or Lyell's syndrome, complicated by a toxic hepatitis. Treatment with a novel combination of intravenous immunoglobulins (IVIG) and N-acetylcysteine (NAC) resulted in an exceptionally fast recovery. A literature research revealed no other cases of patients treated with both NAC and IVIG for the combination of TEN and toxic hepatitis. Because of the rapid clinical recovery, this approach merits further investigation. This case report also illustrates the importance of early suspicion of SJS when an HIV-infected patient treated with nevirapine presents with stomatitis.

Successful Simultaneous Pancreas Kidney Transplantation from Living-Related Donor Against Positive Cross-Match

A positive pretransplant flow cytometry cross-match (FC-XM) allows precise identification of high-risk recipients vulnerable to hyperacute or accelerated rejection after transplantation. Living donor kidney transplant recipient candidates with positive cross-match have been successfully treated with a combination of plasmapheresis (therapeutic plasma exchange, TPEX) and intravenous immunoglobulin (IVIG), achieving conversion to negative cross-match and successful transplant. We report the first successful case of simultaneous pancreas kidney transplant (SPKT) from a living donor (LD) performed against an initially positive FC-XM, converted to negative using a protocol based on TPEX and IVIG in combination with antiCD20 monoclonal antibody. This strategy of overcoming the cross-match barriers in living donation may offer a chance of successful transplantation to highly sensitized candidates for SPKT, for whom cadaveric transplant is difficult to achieve.

P300 An HIV-infected patient with nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcystein

P300 An HIV-infected patient with nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcystein

Antiphospholipid syndrome in obstetrics.

Antiphospholipid syndrome (APLS) in pregnancy is characterized by the presence of autoantibodies in association with recurrent fetal loss and severe complications such as preeclampsia, fetal growth retardation, or placental insufficiency. The most clinically important serologic markers are lupus anticoagulant, anticardiolipin antibodies, and recently anti-beta-2-glycoprotein 1 antibodies. At present, standardization does not exist and a definitive association between specific clinical manifestation and antibody level is not yet known. Experimental data gave evidence that passive transfer of antiphospholipid antibodies result in clinical manifestation of APLS, that is, fetal loss and thrombocytopenia. Treatment with heparin, aspirin, or intravenous immunoglobulins decreased the fetal loss rate. Treatment regimens in human are very difficult to interpret. Evidence from two prospective studies supported treatment with heparin and aspirin to improve pregnancy outcome. The risk of preeclampsia and placental insufficiency was substantial and occurred in 50% of patients. The general failure rate of heparin/aspirin treatment is approximately 30%. In such cases intravenous immunoglobulin in combination with heparin and aspirin has been used to treat APLS.

The simultaneous presentation of sarcoidosis and common variable immune deficiency

Sarcoidosis and common variable immune deficiency can rarely present simultaneously in the same individual. We describe a child who presented with both disorders. The diagnosis of sarcoidosis was delayed because of the atypical appearances of the liver biopsy. She failed to respond to intravenous immunoglobulin but improved once cyclosporin and corticosteroids were added to her treatment regimen. It is important that the co-existence of both disorders is recognised so that treatment with a combination of intravenous immunoglobulin and immunosuppression can be in instituted to treat both the immune deficiency as well as the granulomatous disorder. As illustrated here, patients may fail to respond if either modality is used alone.

Combined Immunoglobulin and Azathioprine in Multiple Sclerosis

In an attempt to prevent exacerbations of multiple sclerosis, immunoglobulin therapy was combined with azathioprine (AZA). Intravenous immunoglobulin (IVIG) 2 g/kg was given in divided doses over 3 consecutive days followed by monthly booster doses (0.2 g/kg) for 3 years to 38 patients with relapsing-remitting multiple sclerosis (MS). In the 34 patients who completed the trial, the relapse rate decreased (from 1.7 relapses per year to 0 during the 3-year trial period). The Kurtzke Expanded Disability Status Scale decreased from 3.4 ± 0.72 to 3.0 ± 0.70. The results suggest that combined IVIG and AZA suppress the ongoing pathologic process in relapsing-remitting MS.

High Dose Intravenous Immunoglobulin in Autoimmune Rheumatic Disorders

Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery.

Section Review: Biologicals & Immunologicals: New insights into the pathogenesis and treatment of cytomegalovirus

There is now increasing evidence that CMV disease results not only from the cytopathogenic effects of the virus itself but also from a CMV-induced immunologic reaction. In addition, CMV can affect both haematopoietic progenitor cells and stromal cell functions, resulting in lympho- and myelosuppression. These observations emphasise the potential benefit of immunological approaches to the treatment of CMV disease. The most promising approach to the prevention of CMV disease in transplant recipients is clearly adoptive transfer of CMV specific T-cell clones from the donor. However, at present, this approach remains experimental and restricted to a small number of patients. Combination of intravenous immunoglobulin (IVIG) and ganciclovir (GCV) is currently the most successful treatment for CMV pneumonia but this approach remains unsatisfactory. It is thus of major importance to distinguish CMV infection from CMV disease in an attempt to prevent the morbidity and mortality of CMV disease by prophylactic or pr...

Efficacy of passive immunotherapy in experimental postsplenectomy sepsis due to Haemophilus influenzae type B

In an effort to develop a more effective therapy for postsplenectomy sepsis, ceftriaxone and human intravenous immunoglobulin (IVIG), alone and in combination, were evaluated for their efficacy against experimental Haemophilus influenzae type B (Hib) bacteremia in splenectomized and sham-operated infant rats. Five-day-old animals had either a splenectomy or sham operation. At 12 days of age, they were challenged intraperitoneally with Hib. Fifteen hours later blood specimens were obtained for quantitative bacterial cultures, and immediately thereafter therapy was started with ceftriaxone, IVIG, combination of ceftriaxone and IVIG, or albumin (control). Quantitative blood cultures were repeated 24 and 48 hours after the treatment. Prior to the treatments, splenectomized animals had significantly higher bacterial counts in blood when compared with sham-operated animals ( P < .001). Splenectomized animals receiving IVIG, ceftriaxone, or the combination of IVIG and ceftriaxone had significantly increased bacterial clearance from blood when compared with the controls ( P < .01). In addition, animals treated with ceftriaxone or the combination of IVIG and ceftriaxone had significantly increased bacterial clearance compared with the IVIG alone treatment group ( P < .01). Overall, the mortality was significantly higher in splenectomized animals compared with the sham-operated animals ( P < .05). The control animals had significantly higher mortality compared with the IVIG, ceftriaxone, and combined ceftriaxone and IVIG treatment groups ( P < .05). There were no detrimental effects of combining IVIG and ceftriaxone together.

Intravenous immunoglobulin in combination with other prophylactic and therapeutic measures

TransfusionVolume 32, Issue 1 p. 72-82 Intravenous immunoglobulin in combination with other prophylactic and therapeutic measures U. E. Nydegger MD, Corresponding Author U. E. Nydegger MD1Swiss Red Cross Blood Transfusion Service, and Head, Division of Transfusion Medicine, Central Hematology Laboratory, Inselspital, CH-3010 Bern, Switzerland.Search for more papers by this author U. E. Nydegger MD, Corresponding Author U. E. Nydegger MD1Swiss Red Cross Blood Transfusion Service, and Head, Division of Transfusion Medicine, Central Hematology Laboratory, Inselspital, CH-3010 Bern, Switzerland.Search for more papers by this author First published: January 1992 https://doi.org/10.1046/j.1537-2995.1992.32192116438.xCitations: 16Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume32, Issue1January 1992Pages 72-82 RelatedInformation

Pneumocystis Carinii Pneumonia in Thymoma with Hypogammaglobulinaemia: Successful Outcome of Therapy Including IV IgG Replacement

A 66-year-old patient presented with Pneumocystis carinii Pneumonia (PCP) and was found to have hypogammaglobulinaemia, associated with a thymoma that had been resected 17 months earlier. Only one previous case of PCP in association with a thymoma and hypogammaglobulinaemia has been reported, in which the patient died. We report another such patient who was successfully treated with a combination of intravenous immunoglobulin and high dose cotrimoxazole.

Enhanced Killing of Group B Streptococci In Vitro by Penicillin and Opsonophagocytosis with Intravenous Immunoglobulin

Combined effects of intravenous immunoglobulin (IVIG) and antibiotics in killing bacteria are of interest with broadening clinical use of IVIG. Since the kinetics of killing by these agents differ and each may influence the outcome of the other, it is difficult to evaluate combination effects in vitro. Conditions were developed to measure killing of group B streptococci (GBS), type III strain M732, by an opsonic mixture with IVIG, fresh serum, and human polymorphonuclear leukocytes (PMNL) with or without penicillin. Bacterial killing was observed with the opsonic IVIG mixture, penicillin, and the opsonic IVIG mixture plus penicillin at 1 h. The effect of the combination was greater than the sum of the effects of two separate incubations. The enhanced killing was evident for up to 18 h. By 24 h, the killing by the combination was no greater than that by penicillin alone. A similar pattern of GBS killing was observed with cord blood PMNL, six different GBS type III strains, and pretreatment of GBS with either IVIG or penicillin. These effects suggest that the combination of IVIG and penicillin has potential for use in the treatment of neonatal GBS infections.