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Long Term Response in a Patient with ITP Following Low Dose Anti-D Immunoglobulin Therapy
Autoimmunity
Abstract
A patient with chronic ITP relapsed after conventional therapy but following an infusion with low dose anti D (Rho) immunoglobulin, she entered a remission which has now lasted 10 months. This is difficult to explain on the basis of long term macrophage Fc receptor blockade and suggests an alternative mechanism of action.
Five patients with ITP were treated with 2 gram intravenous infusions of intramuscular human non specific immunoglobulin (IMIg). Increased platelet counts similar to those achieved with intravenous Rhesus anti D immunoglobulin were observed in four patients. 5000 iu anti D immunoglobulin contain up to 2 g of IMIg, and the clinical responses seen in ITP patients treated with anti D may therefore be attributed to this non specific fraction. This was supported by the in vitro finding that adsorption of the rhesus specific IgG from anti D immunoglobulin did not reduce its inhibitory effect on monocyte Fc receptor function. The dose of intravenous IMIg which produced a response in ITP was less than 2% of the recommended standard dose of intravenous immunoglobulin. This correlated with the higher concentration of IgG polymers in IMIg, and we suggest therefore that the mechanism of action of this material is due to the inhibitory effect of its polymeric IgG fraction on low affinity monocyte/phagocyte Fc receptors.
Medical management of chronic idiopathic thrombocytopenia (ITP) in childhood often fails [20, 26], which is why splenectomy is the recommended method of choice in these cases. However, surgery may not guarantee permanent therapeutic effects either: removal of the spleen may be accompanied by an increased risk of postsplenectomy infections (overwhelming post-splenectomy infection, OPSI syndrome). For these reasons we carried out partial splenic resection in nine children with chronic ITP. The aim of this procedure was to influence the course of chronic ITP by saving the immunological competence of children. Results from a clinical, hematological, and immunological point of view are discussed.
Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually during the treatment and 1 remained unchanged. Conclusion - Rhesus anti-D immunoglobulin has no beneficial effect in patients with autoimmune neuropathy.
Summary Anti-Rho(D) immunoglobulin (anti-D) contained more high molecular weight (HMW) IgG polymers than intravenous non-specific immunoglobulin (i.v. Ig). The low-dose anti-D and high-dose i.v. Ig regimens used to treat idiopathic thrombocytopenic purpura (ITP) therefore contained similar total amounts of HMW IgG. In vitro, the HMW IgG polymers were more effective competitive inhibitors of monocyte phagocyte Fc receptors than monomeric IgG. The IgG subclass composition of anti-D and i.v. Ig were both similar to normal human plasma. We conclude that the HMW IgG content but not the IgG subclass composition of anti-D may explain its low-dose therapeutic efficacy in ITP.
The development of an online version of the Trinity College Dublin Printed Catalogue, which list books from the 14th C to 1872, is described. The principal benefit of the system is the ability to search on words and word stems in the title field. As the entries are in at least fourteen languages the language of each Roman script entry was determined, with a success rate of over 90%. The image of the entry from the catalogue is displayed. This hides the OCR errors.KeywordsRecognition RateTrinity CollegeOptical Character RecognitionFunction WordOnline CatalogueThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Significant advances have been made in the understanding of organ specific autoimmune disorders and parallels can now be drawn with autoimmune thrombocytopenia (AITP). In AITP, the platelet surface glycoprotein target antigen epitopes are now well characterised and reliable autoantibody assays are available. Most patients can be treated effectively, and in refractory patients, experimental treatment has given new insights into the pathogenesis of the disorder. This article reviews the immunological aspects of AITP and suggests a diagnostic and therapeutic strategy in responsive and refractory patients.
Five patients with ITP were treated with 2 gram intravenous infusions of intramuscular human non specific immunoglobulin (IMIg). Increased platelet counts similar to those achieved with intravenous Rhesus anti D immunoglobulin were observed in four patients. 5000 iu anti D immunoglobulin contain up to 2 g of IMIg, and the clinical responses seen in ITP patients treated with anti D may therefore be attributed to this non specific fraction. This was supported by the in vitro finding that adsorption of the rhesus specific IgG from anti D immunoglobulin did not reduce its inhibitory effect on monocyte Fc receptor function. The dose of intravenous IMIg which produced a response in ITP was less than 2% of the recommended standard dose of intravenous immunoglobulin. This correlated with the higher concentration of IgG polymers in IMIg, and we suggest therefore that the mechanism of action of this material is due to the inhibitory effect of its polymeric IgG fraction on low affinity monocyte/phagocyte Fc receptors.
In chronic autoimmune thrombocytopenic purpura (AITP), an indirect monoclonal antibody immobilised platelet antigen (MAIPA) assay detected serum glycoprotein (GP) IIb/IIIa antibodies in 16/39 (41%) cases. In patients with clinically active AITP, a direct MAIPA assay detected platelet-associated GP IIb/IIIa kantibodies in 8/13 (62%) cases. Platelet bound and serum antibody concentrations suggested a high antibody affinity for platelet membrane glycoprotein IIb/IIIa. Five AITP patients with platelet associated glycoprotein IIb/IIIa antibodies were treated with intravenous anti D immunoglobulin. All showed an increase in platelet counts and a decrease in platelet associated autoantibody. These responses could be due to immunosuppressive anti-idiotype antibodies in anti D immunoglobulin.
An 8 year old female child was treated with steroid hormones, anabolic steroid hormones and high dose gamma-globulin therapy for 2 years since being diagnosed with idiopathic thrombocytopenic purpura at the age of 6 years. Treatment produced only transient efficacy, and thrombocytopenia persisted. A scintigram taken 2 years after the onset of the disease using [125I]-labelled heated auto red cells revealed accumulation of radioactivities in the spleen, and therefore splenectomy was performed. However, thrombocytopenia (10 x 10(9)/L) developed again 3 weeks after the operation, for which she was treated again with high dose gamma-globulin with only transient recovery. Then, anti-D immunoglobulin was injected intramuscularly at 250 micrograms per dose for a total of four doses and the platelet count was restored to the normal range. Since then her platelet count has been maintained higher than 200 x 10(9)/L for these 11 months. The scintigram taken after splenectomy showed an accumulation of radioactivities in the liver. After administration of anti-D immunoglobulin, transient subclinical hemolysis appeared. The mechanism whereby anti-D immunoglobulin exerts the efficacy described here may be considered to be by blockage of Fc receptors of macrophages, as is the case for high dose gamma-globulin therapy. However, since the recovery in the platelet count persisted, it appears that changes in the immune system other than the above described mechanism have contributed to the recovery.
The platelet count increases transiently after treatment with polyclonal anti-D in about 50 percent of D+ patients with autoimmune thrombocytopenic purpura (AITP). The effect is usually attributed to macrophage Fc-receptor blockade by antibody-coated red cells. As polyclonal anti-D is in limited supply, prospective testing was performed on a monoclonal anti-D (MoAb D) in such patients.
Seven D+ patients with chronic AITP received MoAb D intravenously at doses of 47 to 95 microg per kg of body weight. Response was assessed by studying platelet count increment. Hemolysis and red cell-bound MoAb D were measured before and after MoAb D administration.
MoAb D red cell binding was demonstrated in all patients at a ratio higher than that observed in AITP patients successfully treated with polyclonal anti-D. However, little or no platelet count increment was observed in six patients, while a transient response was observed in only one (platelet count 97 x 10(9)/L before MoAb D infusion and 163 x 10(9)/L 4 days later). Furthermore, because five patients showed signs of hemolysis and two became anemic, higher doses of MoAb D should be used only with caution in patients with AITP.
The MoAb D used in this study cannot be proposed as an alternative treatment for patients with AITP.
We report the results of intravenous anti-D (WinRho, WinRho SD) therapy in 261 non-splenectomized patients treated at the New York Hospital-Cornell Medical Center over the period from 1987 to 1994. Children (n = 124) and adult patients (n = 137) with classic immune thrombocytopenic purpura (ITP; n = 156) or human immunodeficiency virus (HIV) related thrombocytopenia (n = 105) and acute (n = 75) or chronic (n = 186) disease at the time of the initial anti-D treatment were studied. In addition, 11 previously splenectomized patients were treated as a separate group. Our objectives were to evaluate the following. (1) Efficacy of anti-D: The response after the initial infusion was analyzed according to clinical parameters, such as patient's age, HIV status, gender, disease duration, pretreatment platelet count, and hemoglobin value, as well as treatment-related factors, including the dose of anti-D, the solvent detergent treatment of the preparation, and the type of administration. (2) Use of anti-D as maintenance therapy: The duration of response after the initial infusion and the results of subsequent treatments were evaluated. (3) Safety/toxicity of anti-D: Postinfusion reactions and hemoglobin decrease after treatment were studied. Anti-D is a safe treatment providing a hemostatic platelet increase in greater than 70% of the Rh+ non-splenectomized patients. The group with the best results is HIV- children, but all patient groups respond and the effect lasts more than 21 days in 50% of the responders. Duration of response is not influenced by HIV status; furthermore, HIV+ patients show no adverse effects on hemoglobin decrease or HIV disease progression. Patients with chronic ITP after splenectomy have minimal or no response to intravenous anti-D.
Twenty-one patients with autoimmune thrombocytopaenic purpura (AITP) were treated with anti-D immunoglobulin. There was no significant difference with low and high dose anti-D treatment in the platelet count response between homozygous and heterozygous Rh(D) positive patients. The heterogeneous responses seen in Rh(D) positive AITP patients treated with anti-D immunoglobulin cannot therefore be explained by differences in Rh(D) phenotypes.
Approximately 70% to 80% of Rh-positive adults and children with acute or chronic immune thrombocytopenic purpura or HIV-related thrombocytopenia respond to infusions of anti-D immunoglobulin. The speed of onset of response is slower than that seen with intravenous immunoglobulin. Anti-D immunoglobulin is well tolerated, with occasional adverse reactions similar to those seen in treatment with polyclonal intravenous immunoglobulin, but anemia requiring blood transfusion can occur. Response is generally better in younger patients and those who have responded to other forms of treatment. Inhibition of Fc receptor-mediated platelet destruction by anti-D immunoglobulin-opsonized erythrocytes is the most likely mechanism of action, although the relative ineffectiveness of a monoclonal anti-D immunoglobulin preparation in treatment of immune thrombocytopenic purpura suggests that other mechanisms may exist. Hepatitis C has been transmitted by intravenous anti-D immunoglobulin preparations when used in the prevention of Rh immunization, prior to the introduction of screening donor plasma for hepatitis C virus antibodies. However, an intravenous solvent-detergent-treated preparation is now available.
Medical history, physical examination, and laboratory testing are essential to arriving at the diagnosis of acute immune thrombocytopenic purpura (ITP). A history of recent viral illness occurs in about half of the pediatric patients who present with acute symptoms of ITP. The physical examination is normal except for purpura; a complete blood cell count with a differential white blood cell count can be used to confirm the diagnosis of acute ITP. Treatment decisions for acute ITP remain controversial. Treatment generally is designed to prevent life-threatening complications, such as intracranial hemorrhage, and may include single or combination therapy with corticosteroids, intravenous immunoglobulin (IVIg), anti-D, and splenectomy. Corticosteroids are inexpensive and offer an alluring option, especially in the recent era of cost-containment. The often slow platelet response and the potentially severe adverse effects of corticosteroid therapy are frequently a deterrent. IVIg usually leads to a rapid rise in platelet count; however, IVIg is very expensive and adverse effects associated with its infusion are common and sometimes troublesome. The role of anti-D in acute ITP is still evolving. It is similar to IVIg in platelet response and is considerably less expensive. Some degree of hemolysis, the main adverse reaction with anti-D, is inevitable due to the binding of anti-D antibody to Rh-positive erythrocytes. However, most cases of hemolysis do not require medical intervention. Splenectomy is reserved for refractory thrombocytopenia with life-threatening hemorrhage in acute ITP or after recurrent severe thrombocytopenia in chronic ITP. Other immunomodulatory therapies are also discussed.
To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy.
Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months.
Two patients worsened gradually during the treatment and 1 remained unchanged.
Rhesus anti-D immunoglobulin has no beneficial effect in patients with autoimmune neuropathy.
The use of i.v. anti-Rh(D) IgG for conditions other than prevention of Rh(D) sensitization is discussed. Besides highlighting the platelet response in ATP, a putative distinctive effect on the hemorrhagic threshold is suggested. Accordingly, we have included discussion of cases of aplastic anemia, myelodysplasia, heavy chemotherapy, coagulation deficiency, and senile vascular atrophy. We have also considered attempts to replace the high-dose pooled i.v. IgG (IVIG) with the much smaller amounts of IgG present in anti-Rh(D) preparations used to prevent Rh-sensitization in pregnancy. Both Fc and variable fragments of the IgG molecule may play a role, the former potentiated by manufacture-induced IgG aggregation and the latter by donor hypersensitization. A role for IgG-anti-F(ab')2 molecules cannot be ruled out.
Presented here are 16 case studies of adults with immune (idiopathic) thrombocytopenic purpura (ITP); 5 were treated at Hackensack University Medical Center (HUMC), Hackensack, NJ, and 11 were treated at the Allegheny University Hospital (AUH), Medical College of Pennsylvania. Four of the 5 patients at HUMC had initial transient responses to intravenous immunoglobulin G (IVIg) therapy and required large doses of corticosteroids to maintain platelet counts over 50,000 microL. One elderly patient with systemic lupus erythematosus (SLE) had been treated unsuccessfully with corticosteroids and immunosuppressants to maintain her platelet count over 50,000 microL. All 5 patients were given 1 or 2 doses of anti-D at 50 microg/kg, leading to complete resolution of ITP. Following anti-D therapy, patients were tapered off corticosteroids and currently remain in complete remission with platelet counts over 100,000/ microL. The mechanism of action of anti-D in ITP remains unclear and requires further study. Treatment of the 11 patients at AUH began with corticosteroids, which resulted in no durable therapeutic response. Anti-D was then given at 50 microg/kg, and this provoked an excellent response with a prompt recovery of platelet levels to 100,000/ microL, after which active treatment was halted. Patients were monitored by direct office visit every 3 months unless a clinical indication required an earlier return. If the patient's platelets dropped below 100,000/ microL, they were first given prednisone. As of the last follow-up, all 11 patients remain stable and no patients have required splenectomy.
High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.
High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000–790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3–4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2–10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.
The rapid rise in platelet count after immunoglobulin treatment in acute and chronic forms of idiopathic thrombocytopenic purpura (ITP), autoimmune neutropenia, and post-transfusion purpura is well documented. It is suggested that the rise in platelet count is due to competitive inhibition of the macrophage binding of platelets by preferential sequestration of immunoglobulin-coated red blood cells. Measurement of haptoglobin levels, a sensitive indicator of haemolysis, suggests that clinically inapparent haemolysis occurs during immunoglobulin therapy of ITP patients. In-vitro experiments confirm that there is immunoglobulin coating of red blood cells. The hypothesis is further supported by the findings that immunoglobulin treatment in autoimmune haemolytic anaemia is ineffective, and that platelet counts rise in some ITP patients after induction of a mild haemolytic syndrome by injection of anti-Rh0 (D).
Twenty-three courses of i.v. anti-D (Rho) immunoglobulin were administered to 13 Rh D-positive patients with chronic idiopathic thrombocytopenia (ITP). Clinically significant responses were seen in a proportion of patients treated with 500-2500 i.u. anti-D, but all those treated with 12,500 i.u. (180 i.u./kg) responded. Patients refractory to other forms of treatment responded well to anti-D, and previous splenectomy did not influence the clinical response. No adverse reactions were observed. The anti-D response was preceded by a lag period of 3-16 days and was maintained for 14-145 days. Platelet-associated IgG was increased after treatment, due to improved survival of immunosensitized platelets or platelet Fc receptor binding of high molecular weight IgG in the therapeutic material. There was no clinical or biochemical evidence of haemolysis. The erythrocyte direct Coombs' test remained positive for 3-45 days, and histological examination of splenic material showed no erythrophagocytosis. We conclude that anti-D (Rho) immunoglobulin is a safe and effective treatment for chronic ITP and that the therapeutic dose is now established in standardized units. The mechanism of action appears to be complex and is probably not due to macrophage Fc receptor blockade with immunosensitized red cells.
THE production of antiplatelet antibodies and removal of IgG-coated platelets by the mononuclear phagocyte system play an important part in the pathogenesis of immune thrombocytopenic purpura. The coating of platelets with immunoglobulin results in their removal in the spleen and liver, presumably by receptors for the Fc fragment of IgG (Fcγ).1 , 2 Prolongation of Fcγ-receptor-mediated clearance of opsonized red cells after splenectomy1 , 3 and infusions of high doses of intravenous gamma globulin,4 , 5 in conjunction with favorable clinical responses to these therapies, support this hypothesis. Some patients, however, respond to neither of these treatments nor to other, less specific forms of immunosuppression, such . . .
We have recently reported that a rise of platelet numbers in ITP can be induced by blockade of the RES with antibody-coated red blood cells. We now present a collaborative study in which 15 Rhesus-positive children with ITP (nine boys and six girls aged 1-15 years) were treated with low-dose anti-D. Ten patients had chronic ITP (duration 6-47 months), five had acute ITP. Doses of 28-50 micrograms anti-D/kg bodyweight per course were given intravenously. In all patients clinical signs of bleeding ceased and platelet counts were elevated. An excellent, good or fair response with platelet increments of greater than 100, 50-100, or 20-50 X 10(9)/l, respectively, was observed in 19, 7, and 12 out of 45 courses in chronic ITP, and in 4, 1, and 2 out of 8 courses in acute ITP. The platelet increase (greater than 40 X 10(9)/l) persisted for 10 to over 360 days in chronic ITP. There were no untoward side reactions. Haemoglobin values remained stable in all patients but laboratory signs of mild, compensated haemolysis ensued. The direct antiglobulin test became positive in all cases due to anti-D IgG. Previous therapy of patients with chronic ITP included high-dose immunoglobulins and prednisone. These regimens were both effective but remissions were short. We conclude that anti-D therapy is an effective and safe form of treatment in childhood ITP.
Intravenous immune globulin (IVIG) is indicated for IgG replacement in antibody deficiency syndromes and as immune-regulatory therapy in some autoimmune diseases. Two case histories, illustrate both aspects of IVIG therapy.
1. Patient 1 is a 24-year-old male with agammaglobulinemia. He was successively treated with monthly IMIG, paternal plasma, and then over the last 5 years, IVIG. On IgG doses of 250 mg/kg q/4 weeks, IgG trough levels remained below 200 mg IgG/dl. IgG half-life was reduced. Although asymptomatic for prolonged periods of time, he eventually developed clinically evident inflammatory bowel disease. Optimal IVIG replacement therapy requires normal IgG half-life and adequate IgG bough levels.
2. Patient 2 is a 12-year-old girl with autoimmune neutropenia, recurrent skin infections, and items unresponsive to antibiotics and to steroid therapy. IVIG at a dose of 3,000 mg/IgG/kg over 3 days significantly increased her neutrophil count. Subsequently, she has required 1,000 mg/kg of IVIG q/4 weeks for maintenance. Antineutrophil autoantibodies have persisted. There is synergism of IVIG -with high doses of corticosteroids. The mechanism of action of IVIG seems to involve a blockage of the RES system.
IVIG therapy is safe even at high doses for most patients. However, anaphylactic reactions have been observed in IgA-deficiem patients with IgE anti-IgA antibodies. The full spectrum of therapeutic applications of IVIG is still being explored, for some patients self-infusion of IVIG at home is an appealing treatment alternative.
Transient efficacy of high-dose intravenous immunoglobulin infusions (HDI) is widely demonstrated in autoimmune thrombocytopenic purpura (AITP). A trial involving repeated injections of HDI was conducted in two adult patients with chronic AITP in order to evaluate their long-term efficacy in refractory forms and their ability to obviate splenectomy. Both patients received 2 g/kg body weight of polyvalent intact intravenous immunoglobulin followed by seven and eight boosters (0.8 to 1.2 g/kg body weight) when the platelet count decreased. It was found that the injections could be spaced progressively. The platelet count remained normal 200 and 800 days after the end of the treatment. The demonstration of the possible long-term efficacy of repeated injections of intravenous immunoglobulin encourages us to recommend this safe therapy for patients with chronic AITP.
Seven children with chronic or intermittent and six with acute idiopathic thrombocytopenic purpura (ITP) were treated with large intravenous doses of polyvalent, intact immunoglobulin (Ig). In all patients the platelet count rose sharply within 5 days, but the initial response and the subsequent course varied from patient to patient. Among children with chronic ITP the initial response was more marked in splenectomised than in non-splenectomised patients. Among those with acute ITP the two who remained Ig dependent had a smaller initial response than the four patients who required no maintenance treatment. During the 90-110 days of observation five of six patients with chronic ITP could be maintained with Ig alone. No untoward effects of Ig therapy were observed.
The rapid rise in platelet count after immunoglobulin treatment in acute and chronic forms of idiopathic thrombocytopenic purpura (ITP), autoimmune neutropenia, and post-transfusion purpura is well documented. It is suggested that the rise in platelet count is due to competitive inhibition of the macrophage binding of platelets by preferential sequestration of immunoglobulin-coated red blood cells. Measurement of haptoglobin levels, a sensitive indicator of haemolysis, suggests that clinically inapparent haemolysis occurs during immunoglobulin therapy of ITP patients. In-vitro experiments confirm that there is immunoglobulin coating of red blood cells. The hypothesis is further supported by the findings that immunoglobulin treatment in autoimmune haemolytic anaemia is ineffective, and that platelet counts rise in some ITP patients after induction of a mild haemolytic syndrome by injection of anti-Rho (D).
In two patients with high-titre autoantibodies to antihaemophilic factor (VIIIc), treatment with high-dose intravenous immunoglobulin (IVIg) resulted in rapid and prolonged, although not total, suppression of antibody. IVIg also inhibited anti-VIIIc activity in patients' plasma in vitro; IVIg and F(ab')2 fragments from IVIg inhibited anti-VIIIc activity of the IgG fraction and of the Fab'2 fragments of the IgG fraction from patients' plasma, indicating that the in-vivo effect of IVIg was due to the presence in the therapeutic immunoglobulins of anti-idiotypic antibodies against idiotypes expressed by anti-VIIIc autoantibodies. In contrast, IVIg had little or no effect on antibody titre in two haemophilic patients with anti-VIIIc alloantibodies. These observations suggest that IVIg contains anti-idiotypes against autoantibodies and may be effective in the treatment of some autoimmune diseases through idiotypic/anti-idiotypic interactions.
Intravenous IgG in adult autoimmune thrombocytopaenia- an update
- A Newland
- Newland A C
Intravenous gammaglobulin treatment of chronic ITP
- J B Bussel
- R P Kimberley
- R D Inman
- I Schulman
- Rundels Cunningham
- C Cheung
- N Smethwick
- E O'malley
- O Barundun
- S Hilgartner
- Bussel J B
Treatment of chronic idiopathic thrombocytopenia with anti-D(Rho) immunoglobulin: its effectiveness, safety and mechanism of action
- B J Boughton
- R Chakraverty
- T B Baglin
- A Simpson
- G Galvin
- P Rose
- P Roholava
Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma receptor antibody
- S B Clarkson
- J B Bussel
- R P Kimberly
- J E Vannsky
- R L Nachman
- J Unkeless
Clinical uses of immune globulin
- R U Sorensen
- M Kallick
Anti Rh (D) immunoglobulin for immune thrombocytopenic purpura
- T P Baglin
- M P Smith
- B Boughton
- Baglin T P