Effect Of Intravenous Immunoglobulin Treatment Research Articles

Сучасні підходи до вакцинації в дітей з різними варіантами первинних та вторинних імунодефіцитів (огляд літератури)

Chronic disease and immunosuppression increase the risk of vaccine-preventable infections, complications, and mortality from infectious diseases. Safe vaccination and achieving an adequate serological response to vaccination are crucial aspects of the management of such patients. Purpose - to analyze data from domestic and foreign medical literature regarding modern approaches to vaccination of children with various primary and secondary immunodeficiency diseases. The majority of children with primary immunodeficiency who have preserved antibody production can demonstrate an immune response to vaccination, but this response can be rapidly lost over time. Limitations to vaccinating children with primary immunodeficiency are related to the use of live vaccines in conditions where the cellular immune system is compromised. Patients with primary antibody deficiency are treated with immunoglobulin preparations and depend on the presence of specific antibodies at a protective level against infectious pathogens, including vaccine-preventable infections. Several studies have shown the effectiveness of intravenous immunoglobulin treatment in reducing the number and severity of infections in patients with humoral deficiency. The majority of children with rheumatic diseases vaccinated according to the Schedule of Routine Immunisations before starting immunosuppressive therapy have protective antibody levels against vaccine-preventable infections. All non-live vaccines can be administered without restrictions, but should be administered two weeks before immunosuppressive therapy to increase immunogenicity. Children receiving high doses of immunosuppressive therapy should avoid receiving live attenuated vaccines. No conflict of interests was declared by the author.

Clinical features of 8 patients with multifocal motor neuropathy in the long-term follow-up

To clarify the clinical and long-term characteristics of multifocal motor neuropathy (MMN). We retrospectively evaluated data from 8 consecutive MMN patients in Yamaguchi University Hospital from 2005 to 2020. Clinical information including dominant hand, occupations, hobbies, nerve conduction data, protein level in cerebrospinal fluid (CSF), responsiveness to intravenous immunoglobulin (IVIg) therapy as initial therapy as well as maintenance therapy were collected. Unilateral upper limb was initially affected in all patients and a dominant upper extremity was affected in six of them. Seven patients had occupations or hobbies which were associated with overuse of their dominant upper extremity. CSF protein level was normal or slightly elevated. Nerve conduction studies showed conduction blocks in 4 cases. Effectiveness of IVIg treatment as initial therapy was observed in all patients. Maintenance therapy was not needed in 2 patients because of mild symptoms with stable clinical course. Long-term maintenance therapy with immunoglobulin was effective in 5 patients during the follow-up period. Dominant upper extremity was frequently affected and most patients had job or habit associated with its overuse, suggesting that physical overload induces inflammation or demyelination in MMN. IVIg was commonly effective as both introduction and long-term maintenance therapies. Complete remission was achieved after several IVIg treatments in some patients.

Longer-term effects of intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: Who benefits?

Intravenous immunoglobulins (IVIg) represent an established cornerstone for the immunotherapy of chronic inflammatory demyelinating polyneuropathy (CIDP). Efficacy of IVIg for CIDP was proven in a large phase III trial. Yet, data on longer-term efficacy and effects in distinct subgroups are scarce. Our trial investigates the long-term efficacy of IVIg treatment in CIDP patients.In this observational real-world study, we retrospectively analyzed 49 CIDP patients receiving continuous IVIg treatment with a mean initial dosage of 87 g (1 g/kg body weight) every 4 weeks over a mean time of 45 months between 2010 and 2018. INCAT-Scores before the start of treatment and at the end of the observation period were compared.Over the observation period, IVIg treatment led to a median improvement of one INCAT score point. Subgroup analyses revealed a more pronounced improvement of INCAT scores in female CIDP patients, individuals with relapsing disease courses, patients with more pronounced motor impairment (higher initial INCAT scores) and in the cohort without need for concomitant other immunotherapies.These data argue for sustained beneficial effects of longer-term immunotherapy with IVIg in CIDP, particularly in females and relapsing disease forms with higher disease activity.

Intravenous immunoglobulin for presumed viral myocarditis in children and adults.

Intravenous immunoglobulin for presumed viral myocarditis in children and adults.

Usefulness of intravenous immunoglobulin administration to sepsis-induced coagulopathy in ICU patients

Intravenous immunoglobulin (IVIG) has been used as adjuvant therapy for severe sepsis patients expecting the anti-inflammatory effect. However, the effects of IVIG have been controversial. The majority of ill patients with SIRS had coagulation abnormalities. In addition, inflammation and coagulation play pivotal roles in the pathogenesis of sepsis. Moreover, the evidence of extensive cross-talk between these two systems has been increasing. The aim of this study is to investigate the effects of IVIG treatment for inflammation and hemostatic abnormality in sepsis patients.

Normal serum levels of immune complexes in postpolio patients

ObjectiveThe pathophysiology of the postpolio syndrome is not fully understood. Increased cytokine levels in cerebrospinal fluid and peripheral blood indicate a systemic inflammatory process. Decreased cytokine levels and the clinical effect of intravenous immunoglobulin treatment further indicate an inflammatory/immunological pathogenesis. The aim of the present study was to evaluate whether an autoimmune process follows the initial infection, by means of analyzing immune complexes. Patients and methodsCirculating immune complexes were analyzed from blood samples of 20 postpolio patients and 95 healthy controls. To compensate for differences in age between patients and controls, a sub-analysis was performed using only the 30 oldest controls. Tumor necrosis factor-inducing properties of polyethylene glycol-precipitated immune complexes were compared between the postpolio patients and 10 healthy controls. ResultsWhen comparing levels in postpolio patients to the whole control group, including the 30 oldest investigated, there were no statistically significant differences. No difference was found in tumor necrosis factor levels induced by immune complexes when comparing patients and controls. ConclusionsThere was no increase in circulating immune complex or in tumor necrosis factor-inducing effects of circulating immune complex between postpolio patients and healthy controls, indicating that the postpolio syndrome is not due to an autoimmune reaction.

Effect of intravenous immunoglobulin treatment on postpartum-related relapses in multiple sclerosis

Effect of intravenous immunoglobulin treatment on postpartum-related relapses in multiple sclerosis

Intravenous immunoglobulin to treat neonatal alloimmune haemolytic disease

Objective: To compare the efficacy of intravenous immunoglobulin (IVIg) and exchange transfusion (EXT) on rhesus haemolytic disease of the newborn (Rh-HDN) and evaluate treatment-related side effects. Methods: Retrospective chart review of two cohorts of newborns with Rh-HDN, treated with (Group 2) or without (Group 1) IVIg. Length of phototherapy, number of EXT, IVIg infusions, intrauterine and top-up red blood cells transfusions, need and permanence of umbilical venous catheter, and length of hospital stay, as well as treatment-related adverse events, were evaluated. Results: Charts of 88 newborns were reviewed (34 in Group 1, 54 in Group 2). Infants in Group 2 received a significantly lower number of EXT, had a lower risk of neurological impairment and needed an umbilical venous catheter for shorter, but required longer phototherapy, longer length of hospital stay, and more top-up transfusions. EXT was associated with a high number of adverse events. Two newborns treated with IVIg developed necrotizing enterocolitis (NEC). Conclusions: IVIg appear as an effective alternative to EXT, reducing the risk of neurological impairment and complications related to EXT. However, side effects of IVIg treatment (higher need of top-up transfusions and longer hospital stay) should be taken into account and the risk of NEC should be carefully monitored during treatment.

Effect of Intravenous Immunoglobulin Treatment on Pregnancy and Postpartum-Related Relapses in Multiple Sclerosis: A Prospective, Rater-Blinded Analysis (P06.185)

Objective: To evaluate relapse rate and disease progression under immunomodulatory treatment with intravenous immunoglobulin (IVIg) during pregnancy and postpartum period. Background Medical treatment of pregnant and nursing women requires special attention. Licensed disease-modyfying drugs for the treatment of MS should be avoided or are hitherto contraindicated during gestation, pregnancy or lactation. Intravenous immunoglobulin (IVIg), might be the only immunomodulatory treatment that can be recommended for women with MS during this period of life considering safety aspects of the fetus or the newborn. Design/Methods: We analysed 70 women with relapsing remitting MS (RRMS) and 66 pregnancies for at least 12 month after delivery. IVIg administration differed for group 1 and 2 as follows. Group I (n=40) patients were treated with IVIg before gestation, during first trimenon of pregnancy and during postpartum period. Group II (n=24) patients were treated with IVIg starting in between 24 hours after delivery and during lactation. Group III (n=6) patients were untreated during pregnancy and lactation. Relapse rates per woman per year before, and disease progression during and after pregnancy were analysed for the described patient groups. Results: Increase of relapse rate after delivery and relapse rates during first and second trimenon like known from historic cohorts (“Pregnancy in MS group”, Confavreux et al. 1998) turns out lower during IVIg-treatment. We could not find a significant difference considering the relapse rate after delivery depending on the described IVIg-treatment groups. Pregnancy and IVIg-treatment do not exert an influence on disease progression. No serious adverse events were recorded under IVIg treatment. Conclusions: IVIg-treatment for RRMS patients during lactation is an effective option to reduce the incidence of postpartum-related relapses. Further multi-center investigations to prove these data with higher numbers of patients are desirable. Supported by: Analysis was not supported. Disclosure: Dr. Winklemann has received personal compensation for activities with Bayer Pharmaceuticals Corporation and Merck-Serono as a speaker. Dr. Benecke has received personal compensation for activities with Ipsen, Allergan, Inc., and Merz Pharma. Dr. Zettl has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Zettl has received research support from Bayer Healthcare, Biogen Idec, Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience.

Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome

Pain is a common symptom that affects quality of life in patients with post-polio syndrome. An increase in cytokine in the cerebrospinal fluid suggests that inflammation is pathophysiologically important in post-polio syndrome. Intravenous immunoglobulin might therefore be a therapeutic option. The aim of this study was to analyse the effect of intravenous immunoglobulin treatment on pain in post-polio syndrome. An uncontrolled clinical study. Patients with post-polio syndrome and pain (n = 45) underwent a neurological examination and were interviewed about pain before and 6 months after treatment with intravenous immunoglobulin. Pain intensity was measured on a visual analogue scale. The pain was classified according to the International Association for the Study of Pain criteria as neuropathic when it occurred in an area with decreased sensibility, or nociceptive when signs of inflammation and/or painful joints movements were present. After treatment 31/45 (69%) patients were improved, with a mean visual analogue scale decrease from 53 to 42 (p = 0.001). Eighteen patients (40%) had a decrease of 20 or more points on the visual analogue scale. The effect of treatment did not differ regarding age, gender and severity of disability. Two-thirds of 45 patients with post-polio syndrome and pain reported a decrease on the visual analogue scale for pain after treatment with intravenous immunoglobulin, and 40% reported a decrease of 20 or more points on the visual analogue scale.

Effect of intravenous immunoglobulin treatment on brain interferon-gamma and interleukin-6 levels in a rat kindling model

Many studies indicate that intravenous immunoglobulin (IgG) therapy may decrease symptoms of epilepsy. In this study, we assessed the effects of intravenous IgG in an experimental rat kindling model and attempted to elucidate the underlying mechanism of the IgG effect. For induction of kindling, Wistar rats received repeated intraperitoneal injections of picrotoxin. The serum level of neuron-specific enolase (NSE) was measured to determine seizure severity. Interferon (IFN)-gamma and interleukin (IL)-6 levels were measured in rat hippocampus homogenates. The serum NSE level and hippocampal IFN-gamma level were significantly higher in fully kindled, untreated rats compared to unkindled control rats, whereas IL-6 levels were similar in all groups. Intravenous IgG-treated kindled rats showed NSE and IFN-gamma levels similar to those of control rats, along with lower seizure severity and longer seizure latent period than fully kindled, untreated rats. These results indicate that intravenous immunoglobulin exerts a protective effect on the neurons of kindled rats, potentially by downregulating cytokines in the brain. These results shed light on the mechanism by which intravenous immunoglobulin decreases the severity of epileptic seizures.

A pediatric case series of acute hemolysis after administration of intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is commonly used as an immune-modulatory treatment for patients with autoimmune and inflammatory diseases [1]. Antibody-mediated hemolysis of red blood cells (RBCs) after IVIG infusion is a recognized but rare side effect [2]. This retrospective case series describes four pediatric patients at a single institution who developed significant hemolytic reactions after treatment with IVIG for either Kawasaki disease or acute inflammatory demyelinating polyradiculoneuropathy. Patients ranged in age from 5 months to 14 years. The mean decrease in hemoglobin level after IVIG was 5.1 ± 0.36 g/dL (mean ± SD). Three of the four patients required RBC transfusion, and all the patients recovered spontaneously within 1 month of IVIG infusion. This case series illustrates a relatively uncommon, but potentially severe side effect of IVIG treatment, and demonstrates the importance of monitoring hemoglobin levels after IVIG therapy.

Effectiveness of Therapeutic Plasma Exchange in Myasthenia Gravis

Background Myasthenia gravis is the most common primary disorder of neuromuscular transmission, caused by an acquired immunological abnormality. The patients have a weakness of muscles which can sometimes be life threatening. Treatment modalities include administration of anti- cholinesterase drugs, corticosteroids, immunosuppression drugs, thymectomy, therapeutic plasma exchange and intra venous immunoglobulin (IVIg) and permutation and combination of all these therapies. Aim & Objective We conducted a retrospective study in Myasthenia gravis patients to find and compare the effectiveness of IVIg treatment vis-a-vis therapeutic plasma exchange, at our hospital. Material & Methods A total of 60 patients (35 males and 25 females) with a diagnosis of Myasthenia gravis, admitted between 1st January2000 to 31st December 2006 were retrospectively analyzed. Nineteen patients were treated by doing Therapeutic Plasma Exchange (TPE) of approximately 1–1.5 times the patient's plasma volume on Haemonetics cell separator (MCS / MCS 3p) using FFP 80% & Normal Saline 20% as replacement fluid. All the patients had central line in place for doing the procedure. The case files of all these patients were scrutinized and the treatment modalities were compared. The duration of illness, clinical features, need for assisted / mechanical ventilation, hospital stay, number of therapeutic plasma exchanges performed were analyzed. Results Twenty four of the 60 Myasthenic patients (40%) improved clinically on anti-cholinesterase drugs alone. The other 36 patients (60%) underwent thymectomy followed by medications (anti-cholinesterase & cortico-steroids). Twelve of these patients improved their muscle power, recovered clinically and were discharged. Six of the remaining 24 patients (average age 45.6 yrs.) were readmitted with myasthenic crisis or impending myasthenic crisis & were put on TPE as next treatment modality and all 6 responded to treatment. Eighteen patients were given IVIg therapy after they showed non-responsiveness to steroids & or immuno-suppressant drugs. Five of these were of younger age group (average age of 23.6 yrs) & recovered completely with IVIg treatment. Thirteen patients did not show substantial improvement & had to be supplemented with TPE. Ten of these patients responded to treatment (average age of 46.1 yrs) while 3 succumbed to the disease process. Conclusion TPE is a better option as the next line of treatment modality in older patients not responsive to thymectomy & medications. IVIg is the preferred line of treatment in the younger myasthenic patients unresponsive to thymectomy and medications. TPE resulted in less hospital stay and thus decrease in overall expense in treatment.

GM-CSF and pregnancy: evidence of significantly reduced blood concentrations in unexplained recurrent abortion efficiently reverted by intravenous immunoglobulin treatment.

Certain Th-2 cytokines and granulocyte-macrophage colony-stimulating factor (GM-CSF) are propitious for the success of pregnancy and recurrent spontaneous abortion (RSA) is often characterized by a failure of Th-2 type responses. These considerations as well as the use of intravenous immunoglobulin (IVIg) in RSA induced us to evaluate the levels of GM-CSF in normal pregnancies, in pregnant women affected with unexplained RSA and the effects of IVIg treatment. Peripheral blood free GM-CSF was measured by means of a sandwich enzyme immunoassay in 39 healthy women (13 non-pregnant, 26 pregnant) and in 53 RSA patients (11 non-pregnant, 42 pregnant). In 14 pregnant RSA patients GM-CSF was studied also after the very first IVIg infusion (0.5 g/kg body weight). In healthy women we found a significant increase of GM-CSF during pregnancy, in pregnant RSA patients such an increase was not detected. After IVIg, GM-CSF concentrations were almost doubled. GM-CSF is found increased in normal pregnancy and is very low during pregnancy in RSA. IVIg infusions are capable of increasing GM-CSF in pregnant recurrent aborters.

Effect of intravenous immunoglobulin treatment on the Th1/Th2 balance in women with recurrent spontaneous abortions.

The way by which intravenous immunoglobulin (IvIg) acts to prevent immunlogically mediated recurrent spontaneous abortions (RSA) has not been clarified. In the present study, a possible effect of IvIg on the T helper cell (Th1/Th2) balance was investigated in abortions of either alloimmune or autoimmune abnormalities. The study included 21 women treated with IvIg before conception because of a history of RSA characterized by alloimmune abnormalities (n = 15) or associated with anti-phospholipid antibodies (APA) (n = 6). Peripheral blood samples, collected before and 5 days after the first IvIg infusion, were stimulated, and Th1 and Th2 cells were detected by flow-cytometric analysis using a combination of monoclonal antibodies against T-cell surface markers and intracellular interferon (IFN)-gamma and interleukin (IL)-4. The percentage of IFN-gamma-producing (Th1) and IL-4-producing (Th2) cells and the Th1/Th2 ratio were compared between pre- and post-infusion samples. A decrease of Th1 percentage in 66.6% of the cases and a concurrent Th2 percentage increase (47.61%) resulted in a decrease in the Th1/Th2 ratio in most of the cases (76.1%) (p < 0.01). Similar results were found in Group A (Th1/Th2 decreased in 60% of the cases, p < 0.05), while in Group B the effect of IvIg was not clear (Th1/Th2 increased in three and decreased in another three cases). Our finding suggests that IvIg administration in women with alloimmune RSA enhances Th2 polarization. This is not always the case with APA-associated abortions.

Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid: A preliminary study

Objective To report the effects of intravenous immunoglobulin treatment of ten patients with progressive ocular cicatricial pemphigoid who did not respond to conventional immunomodulatory regimens. Design Noncomparative, interventional case series. Participants Ten patients with biopsy-proven progressive cicatricial pemphigoid affecting the eyes who did not respond adequately to other local and systemic immunosuppressive treatment regimens. Intervention Intravenous infusions of pooled human immunoglobulin, 2 to 3 g/kg body weight/cycle, divided over 3 days, and repeated every 2 to 6 weeks. Main outcome measures Reduction in conjunctival inflammation, prevention of progression of subepithelial conjunctival fibrosis, improvement in ocular symptoms (discomfort, photophobia), improved visual acuity, reduction in extraocular mucosal lesions. Results Clinical deterioration was arrested and resolution of chronic conjunctivitis was documented in all ten patients. Maximum therapeutic effect was observed and maintained after a minimum of 4 cycles of therapy; three patients required 12 cycles before disease control. The duration of therapy in these ten patients has been 16 to 23 months (mean, 19.3 months) with no treatment-induced side effects. Extraocular mucosal lesion resolution has occurred in all but one patient. Visual acuity has stabilized or improved in all ten patients, and subjective complaints of discomfort and photophobia have decreased in all patients. Conclusions Intravenous immunoglobulin immunomodulatory therapy can be a safe and effective therapy for otherwise treatment-resistant ocular cicatricial pemphigoid.

Inflammatory parameters and soluble cell adhesion molecules in Swedish children with Kawasaki disease: relationship to cardiac lesions and intravenous immunoglobulin treatment.

The possible use of inflammatory parameters as a predictor of coronary artery lesions (CAL) and the effect of intravenous immunoglobulin (IVIG) treatment in 30 Swedish children with acute Kawasaki disease were investigated. All the patients were treated with IVIG (2 g/kg) and seven of them had CAL. Ten febrile children, hospitalized for treatment of severe infection, and 15 healthy children served as controls. The levels of soluble E-selectin and soluble intercellular adhesion molecule (ICAM)-1 in the Kawasaki patients were elevated in comparison to healthy, but not in comparison to febrile controls. Paired analysis of our patients before and after IVIG therapy during acute disease revealed lowered levels of C-reactive protein, interleukin-6, soluble E-selectin and soluble ICAM-1. We found no statistically significant relationships among any of these parameters as a possible predictor of CAL, but three patients with cardiac sequelae demonstrated high values for these inflammatory parameters. These findings may reflect endothelial activation in connection with vasculitis, and the anti-inflammatory effect of IVIG treatment lowering cytokine levels and subsequently decreasing the expression and shedding of adhesion molecules. In conclusion, we were unable to identify a predictor of CAL in the acute phase. The patients had higher levels of soluble E-selectin and soluble ICAM-1 than did afebrile controls, but not febrile controls. The patients' levels of C-reactive protein, interleukin-6, soluble E-selectin and soluble ICAM-1 were decreased after 1-2d of IVIG treatment.

Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study.

The effect of high dose intravenous immunoglobulin (IVIg) treatment was studied in six patients with multifocal motor neuropathy (MMN). All patients responded to treatment (0.4 g/kg for five consecutive days) in an open trial. The effect of IVIg treatment was confirmed for each patient in a single patient, double blind, placebo controlled trial. Four patients received two IVIg treatments and two placebo treatments, and two patients received one IVIg and one placebo treatment in a randomised order. Five out of six patients responded to IVIg but not to placebo. One patient responded to IVIg in the same manner as to placebo treatment. Thus IVIg treatment can lead to improvement of muscle strength in patients with MMN.

The effect of intravenous immunoglobulin treatment in recurrent acute otitis media

The effect of serial intravenous infusion of human immunoglobulin on the frequency of acute otitis media (AOM) episodes and on other upper respiratory tract infections was prospectively studied in a group of 22 otitis-prone children, 1-4 years old. After pair-matching, the children were allocated to immunoglobulin treatment or to a control group. Increased specific IgG antibody activities against pneumococcal types associated with recurrent AOM (rAOM) were generally achieved, but no significant difference was noted in the frequency of AOM attacks or other respiratory tract infections between the immunoglobulin-treated children and their pair-matched untreated controls. The results indicate that, although serum antibody activities against bacteria associated with AOM are increased by immunoglobulin infusions, this does not prevent the development of AOM in children suffering from rAOM.