Intravenous Γ-globulin Research Articles

Abnormal myocardial mechanics in Kawasaki disease: Rapid response to γ-globulin

Background The time course and rate of recovery of myocardial dysfunction in association with Kawasaki disease in response to intravenous γ-globulin is unknown and may provide mechanistic clues. Methods and Results The acute changes in myocardial contractility in 25 patients with Kawasaki disease were evaluated by noninvasive stress-shortening and stress-velocity analysis. Echocardiograms were performed before and then daily for 4 days during which the patients received γ-globulin 1.6 to 2 g/kg. Before treatment, contractility was abnormally low <2 SD) in 14 patients 56%). Contractility increased significantly 2 SD increase) in 17 68%), including 13 of 14 with depressed contractility and 4 whose initial contractility fell within normal limits. Of the 14 patients with depressed contractility, 8 57%) normalized within 24 hours and a further 5 35.7%) normalized within 6 months. A clinical response to treatment fall in C-reactive protein by 50% and/or resolution of fever within 4 days) was seen in 22 patients 88%). Contractility increased in 17 of the 22 clinical responders and was normal before therapy in the other 5. The 3 patients who did not respond clinically also had no change in contractility with γ-globulin therapy. Long-term (more than 12 months) follow-up was available in 19 patients. All patients had normal contractility at late follow-up. Conclusions More than half the patients with Kawasaki disease have abnormal contractility at presentation. Myocardial response to globulin therapy is associated with rapid improvement in myocardial mechanics, with a high concordance between the clinical and myocardial response to therapy. The speed of recovery suggests that depressed contractility in patients with Kawasaki disease is caused by a rapidly reversible process such as circulating toxins or activated cytokines. Long-term outcome is good even in those patients with slow recovery of myocardial function.

Corticosteroids in the treatment of the acute phase of Kawasaki disease

Objectives: Corticosteroids are considered to be contraindicated during the acute phase of Kawasaki disease (KD) based on unfavorable results in early studies. In our hospital, however, corticosteroids have been used in some cases of KD with satisfactory results. We analyzed outcomes of patients with KD treated with or without corticosteroids. Study design: Medical records of 299 children with KD treated with one of the 4 regimens were reviewed retrospectively. Regimen 1 consisted of aspirin, dipyridamole, and propranolol; regimen 2 was regimen 1 plus prednisolone, 2 mg/kg/d, for 1 week, followed by tapering over 2 weeks; regimen 3 was regimen 1 plus intravenous γ-globulin (IVGG), 200 or 400 mg/kg/d, for 5 consecutive days; and regimen 4 was regimen 1 plus both prednisolone and IVGG. Results: Although patients treated with regimens 2 and 4 were more ill at presentation than those treated with regimens 1 and 3, respectively, the duration of fever was shorter in the former patient groups ( P = .0013). Coronary aneurysms developed least frequently in patients treated with regimen 4 and less frequently with regimen 2 than with regimen 1 ( P = .0730). Multiple regression analysis showed significant reductions of fever and coronary aneurysm incidence with prednisolone ( P < .0001 and P = .0307, respectively). Conclusion: Our data suggest a possible role of corticosteroids in the treatment of the acute phase of KD. (J Pediatr 1999;135:465-9)

Adult respiratory distress syndrome after experimental intravenous γ-globulin concentrate and monocyte-reactive IgG antibodies

We have previously identified non-HLA class I IgG alloantibodies that inhibit monocyte Fc-receptor function. They are involved in the protection of rhesus D-positive infants against red-cell destruction by maternal antibodies. We postulated that such antibodies may have potential therapeutic value for the treatment, prevention, or both of haemolytic disease in neonates and of various other antibody-mediated cytopenias. An experimental -globulin for intravenous administration was prepared from plasma containing such antibodies (monocyte-inhibiting -globulin, MIGG). As part of a prospective study, MIGG was given to a healthy man aged 31 years. He had no history of allergy, did not use medications, and had no febrile illness in the months before the study. The volunteer was typed for HLA (A26, A32, B39, B18 Cw7 DR4, DRw8 DRw52, DRw53 DQw3); serum immunoglobulin concentrations were normal. After the administration of 10 mL MIGG (0·6 g IgG; 0·5 mL/min) the volunteer started to complain of a dry cough and malaise. Manipulation of the infusion needle in his arm was followed by hypotension (decrease from 124/83 mm Hg to 108/67 mm Hg) with a slightly rapid pulse (increase from 61 beats/min to 74 beats/min) without other observable symptoms. The hypotension was mistakenly interpreted to be a vagal reaction. The patient recovered quickly and after 50 min the administration of MIGG was continued. 20 min later he started to cough again and suddenly became very ill with nausea, vomiting, and an increasing feeling of bodily discomfort. 80 mL MIGG (4·8 g IgG) had been infused. Blood pressure fell to 103/62 mm Hg and pulse rate rose to 110 beats/min. He started to produce white foamy sputum that soon became brown-coloured and tinged with blood. On auscultation, fine crepitations were audible at the bases of both lungs. Chest radiography showed diffuse bilateral pulmonary interstitial infiltration with a normal cardiac silhouette characteristic for non-cardiogenic pulmonary oedema (figure). Adult respiratory distress syndrome was suspected and the patient was started on intravenous hydrocortisone (200 mg). After 8 h he deteriorated and his blood pressure decreased further. He was intubated and received mechanical ventilation. Up to 100% oxygen and positive end-expiratory pressure up to 10 mm Hg were required during 4 days. Because the patient remained unstable, therapeutic leucapheresis combined with a 2·5 L plasmapheresis (exchanged with fresh-frozen plasma) procedure was done on day 3 in hospital. He improved clinically and the next day was extubated. We cannot, however, exclude coincidental improvement after this procedure. Subsequent recovery was complete and uneventful. Because

Intravenous γ-globulin inhibits binding of anti-GM 1 to its target antigen : Malik U, Oleksowicz L, Latov N, et al. Ann Neurol39:136–139, 1996

Intravenous γ-globulin inhibits binding of anti-GM 1 to its target antigen : Malik U, Oleksowicz L, Latov N, et al. Ann Neurol39:136–139, 1996

Antenatal management of alloimmune thrombocytopenia with intravenous γ-globulin: A randomized trial of the addition of low-dose steroid to intravenous γ-globulin

OBJECTIVES: Our purposes were to investigate maternal infusions of intravenous γ-globulin used to increase the platelet count in thrombocytopenic fetuses with alloimmune thrombocytopenia, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous γ-globulin. STUDY DESIGN: Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous γ-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous γ-globulin plus 60 mg of prednisone per day (“salvage”). RESULTS: Dexamethasone did not add to the effect of intravenous γ-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/μl ( n = 47) and from the first fetal blood sampling to birth of 69,000/μl ( n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. “Salvage” increased the platelet count in 5 of 10 nonresponders to intravenous γ-globulin. CONCLUSION: Intravenous γ-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia. (AM J OBSTET GYNECOL 1996;174:1414-23.)

Intravenous γ-globulin treatment in a patient with subacute sclerosing panencephalitis

A 10-year-old boy with subacute sclerosing panencephalitis was treated with intravenous γ-globulin and inosiplex and followed for 18 months. Clinical improvement, demonstrated by decreasing scores on the Neurologic Disability Index, was observed. There were no side effects. We recommend intravenous immune globulin as an alternative therapy in the treatment of subacute sclerosing panencephalitis.

High-dose intravenous γ-globulin treatment for hyperimmunoglobulinemia E syndrome

Background: Hyperimmunoglobulinemia syndrome (HIES) is an inflammatory skin disease, and management of it is not satisfactory. However, high-dose intravenous γ-globulin (IVGG) is a safe and effective treatment for Kawasaki disease. Methods: I initially treated two patients with Kawasaki disease, both of whom also had HIES, with IVGG. Subsequently, I treated patients with HIES alone, atopic dermatitis, Kawasaki disease, or idiopathic thrombocytopenic purpura with IVGG and measured serum IgE levels and in vitro spontaneous IgE production by peripheral blood mononuclear cells from patients. Direct effects of IgG on in vitro IgE production were also studied. Results: IVGG treatment remarkably improved severe eczema in patients with HIES with or without Kawasaki disease and in patients with atopic dermatitis. Moreover, serum IgE levels and in vitro spontaneous IgE production were decreased in these patients but not in patients with Kawasaki disease or idiopathic thrombocytopenic purpura. The addition of high concentrations of IgG to cultures of peripheral blood mononuclear cells from patients with HIES or atopic dermatitis decreased in vitro spontaneous IgE production. Moreover, IgG also decreased IgE production by normal B cells stimulated with interleukin-4 plus anti-CD40 monoclonal antibody. Conclusion: IVGG is effective in the treatment of severe eczema in patients with HIES and atopic dermatitis. IVGG also decreased enhanced IgE production both in vivo and in vitro. (J A LLERGY C LIN I MMUNOL 1995;95:771-4.)

Systemic lupus erythematosus complicated by thrombotic microangiopathy

Seven patients with systemic lupus erythematosus (SLE) or SLE-like disease developed thrombotic microangiopathy. Prominent features of their acute illnesses were microangiopathic hemolytic anemia (7), thrombocytopenia (7), fever (1), nervous system disease (4), and renal dysfunction (5). Laboratory data were significant for antinuclear antibody (ANA) (7), DNA (5), low C3 level (3), low C4 level (2), antiphospholipid antibody (6), schistocytes (7), and lactate dehydrogenase > 500 (7). All seven patients received treatment that initially included steroids but later included cyclophosphamide (4), plasma infusion (1), plasmapheresis (5), intravenous γ-globulin (2), anti-platelet agents (2), or vincristine (3). Six patients improved, and one patient expired during treatment. Of the six patients who survived this complication, three expired within the year following their acute illnesses. Histology, available in two cases, showed vascular changes consistent with a microangiopathic process. We conclude that the spectrum of vascular diseases in SLE extends beyond vasculitis to include noninflammatory vascular processes that can cause equally devastating complications.

Effectiveness of High-Dose Intravenous Gamma Globulin Therapy in Acquired von Willebrand's Disease

An 82-year-old patient with acquired von Willebrand’s disease in association with a non-Hodgkin lymphoma and a benign IgG(λ) monoclonal paraproteinaemia is described with severe recurring nasopharyngeal bleedings, who responded poorly to desmopressin (DDAVP) and factor VIII/von Willebrand factor concentrates but was successfully treated with high-dose intravenous γ-globulin therapy.

Putative Mechanisms of the Effect of Intravenous γ-Globulin

Putative Mechanisms of the Effect of Intravenous γ-Globulin

Kawasaki disease in Adelaide: A review

The role of Kawasaki disease (KD) as a contributor to early childhood cardiac morbidity in Adelaide was investigated by a review of hospital admission and case-note data from January 1979 to June 1990. There were 57 episodes in 55 patients. The epidemiological data in this South Australian series are similar to that seen in other Australian and New Zealand centres and correlate better with the clinical data from North America than from Japan. The average age of admission was 3.2 years (median 2.7 years) with 38 and 85% of cases being less than 2 and 5 years respectively. The male to female ratio was 1.5. The incidence of KD in the 0-5 year age group was 3.9 cases per 100,000 children. This series represents a minimum number of cases for this period and illustrates an association of aneurysm-risk with prolonged fever; improved defervescence with the combination of intravenous gamma-globulin (IVGG) and aspirin compared with aspirin alone; and a more severe disease process in the very young. The series supports the efficacy of single dose IVGG therapy. Antibiotics were given prior to diagnosis of KD in 79% of patients, often causing diagnostic confusion with possible drug reactions. The pathogenic mechanisms of KD are reviewed and a new hypothesis is proposed that incorporate mechanisms of vessel pathology resulting from release of endothelin and recognized mediators of endothelial damage including tumour necrosis factor-alpha and interleukin-1 beta.

Intravenous gamma globulin inhibits immunoglobulin production and cytokine mRNA expression in human peripheral blood mononuclear cells

We retrospectively reviewed the effects of intravenous γ-globulin (IVGG) re-treatment of 13 children with Kawasaki disease and persistent or recrudescent fever. Fever and mucocutaneous inflammation resolved within 48 hours in nine patients; fever abated in two other children after a third course of IVGG. We conclude that IVGG re-treatment of Kawasaki disease appears to be safe and may improve the clinical course.

Bacillary peliosis hepatis as a cause of acute anemia in a patient with the acquired immunodeficiency syndrome

A 33-year-old white homosexual man, infected with the human immunodeficiency virus, presented with acute anemia and thrombocytopenia not responsive to transfusions or to treatment with steroids and intravenous γ-globulin. Hematologic workup was compatible with peripheral sequestration or loss of blood cells; however, there was no evidence of gastrointestinal or other sources of hemorrhage, and the only significant finding was a progressive liver enlargement. An abdominal computerized tomographic scan showed a massive homogeneous liver without focal lesions, a very small amount of ascites, and no retroperitoneal fluid collections. A transjugular liver biopsy specimen showed the cystic, blood-filled cavities characteristic of peliosis hepatis. Cavities varied in size, all contained pooled erythrocytes, and some had areas suggestive of thrombi in various stages of organization. Bacteria similar in morphology to those described in bacillary peliosis hepatis were seen in the peliotic spaces. The clinical picture began resolving shortly after treatment with zidovudine and ampicillin/sulbactam was started and had totally resolved 6 months after presentation. This case shows that bacillary peliosis hepatis is a reversible entity that may produce acute sequestration of blood in the liver.

Advances in Early Diagnosis of Perinatal HIV Infection

Early intervention using antiretroviral therapy and prophylaxis for infections has become the standard of care for adults and children infected with human immunodeficiency virus (HIV). Advances in the field of HIV treatment have resulted in improvement in quality and/or duration of life for patients of all ages. Zidovudine therapy is now approved and routinely indicated for treatment of symptomatic HIV-infected children and for those with evidence of immunodeficiency. 1 Prophylaxis for Pneumocystis carinii pneumonia is routinely recommended for children with significant CD4 lymphocyte depletion, and intravenous γ-globulin has been shown to reduce the rate of serious bacterial infections in some HIV-infected chiidren. 2,3 However, for therapeutic interventions to be applied optimally, it is essential for the diagnosis of HIV infection to be made as early in the course as possible, before immunodeficiency and symptomatic illness are manifest. For children with perinatally acquired HIV infection, this is particularly problematic. 4,5

Intravenous γ-globulin in myasthenia gravis: Interaction with anti-acetylcholine receptor autoantibodies

Clinical improvement has been observed in myasthenia gravis patients treated by intravenous immunoglobulin (IVIg). In order to investigate the mechanism of action of these IVIg, we looked for an in vitro interaction between IVIg and the anti-acetylcholine receptor autoantibodies. Significant inhibition by IVIg of anti-acetylcholine receptor autoantibody activity from 30 MG sera was observed and binding of anti-acetylcholine receptor autoantibodies on IVIg was found for four of five myasthenia gravis sera. These observations suggest that IVIg contains Ig directly binding to and inhibiting pathogenic autoantibodies.

Rapid regression of coronary dilatation in Kawasaki disease with intravenous γ-globulin

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Treatment of severe systemic rheumatoid arthritis with intravenous γ-globulin: Earl Silverman, Chaim Roifman, Mark Greenwald, Erwin Gelfand, Bonnie Isacovics, and Ronald Laxer, The Hospital for Sick Children, Toronto, Ontario

Treatment of severe systemic rheumatoid arthritis with intravenous γ-globulin: Earl Silverman, Chaim Roifman, Mark Greenwald, Erwin Gelfand, Bonnie Isacovics, and Ronald Laxer, The Hospital for Sick Children, Toronto, Ontario

Intravenous γ-globulin therapy in systemic lupus erythematosus and immune complex disease

Immune complexes (ICs) are felt to be of primary pathological importance in the mediation of many human glomerular diseases. This is based on the demonstration of Ig and C′ in renal cortex tissue of affected individuals. Systemic lupus erythematosus (SLE) is a prototype IC disease where ICs have been demonstrated in target tissues. Moreover, glomerulonephritis (GN) is a common feature of many autoimmune and infectious diseases associated with IC generation. Current therapeutic alternatives are restricted to immunosuppressive agents. Tomino et al. ( Clin. Exp. Immunol. 58, 42, 1984) demonstrated that glomerular IC deposits could be solubilized with HGG. Palla et al. ( Clin. Nephrol. 26, 314, 1986) treated four membranous nephritis patients with IVGG and had dramatic resolution of proteinuria in three of them. Gaedlicke et al. ( Blut 48, 387, 1984) reported improvement in vasculitis in one of two patients treated with IVGG. We have experienced exacerbation of GN with IVGG therapy in two SLE patients. IVGG is useful in treating the common variable immunodeficiency that occurs in some SLE patients and in treating the immunodeficiency associated with florid nephrotic syndrome. IVGG given to one patient with Henoch-Schönlein purpura resulted in the onset of gross hematuria. In sum, IVGG may be useful in treating specific IC renal diseases by solubilization of circulating or in situ ICs but definitive proof is lacking. In other situations, IVGG may exacerbate the glomerulonephritis, possibly through enhanced IC formation. Furthermore, IVGG may induce modulation of immune responses by induction of auto-anti-idiotypic immunity.

Comparison of intravenous γ-globulin and fresh-frozen plasma infusions in hemolytic-uremic syndrome: K. J. Shath, J. Gill, and N. Leichter, Medical College of Wisconsin, Milwaukee, Wisconsin

Comparison of intravenous γ-globulin and fresh-frozen plasma infusions in hemolytic-uremic syndrome: K. J. Shath, J. Gill, and N. Leichter, Medical College of Wisconsin, Milwaukee, Wisconsin

Effects of intravenous γ-globulin on immune function in pediatric HIV infection: M. Ellaurie and A. Rubinstein, Albert Einstein College of Medicine, Department of Pediatrics, Bronx, New York

Effects of intravenous γ-globulin on immune function in pediatric HIV infection: M. Ellaurie and A. Rubinstein, Albert Einstein College of Medicine, Department of Pediatrics, Bronx, New York