Effect Of Intravenous Immunoglobulin Therapy Research Articles

Effectiveness of intravenous immunoglobulin therapy for invasive group A Streptococcus infection: A Japanese nationwide observational study

ObjectivesInvasive group A Streptococcus infection (iGAS) is a rare but fatal condition. We aimed to evaluate the effectiveness of intravenous immunoglobulin (IVIG) in the treatment of iGAS. MethodsPatients’ data were extracted from a Japanese nationwide database between April 2018 and March 2021. The primary outcome was in-hospital mortality rate, whereas the secondary outcomes were 30-day and 7-day mortality rates. ResultsOverall, 481 patients (median age, 65 years; female, 49.7%) were included in the analysis. The overall mortality rate was 31.0%. After adjusting for background factors, we found that IVIG treatment had no effect on in-hospital mortality (adjusted odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.93-1.04, P = 0.92). Similar results were obtained after propensity score matching (OR: 1.00, 95% CI: 0.62-1.61, P >0.99). The 7-day and 30-day mortality rates were not associated with IVIG treatment. ConclusionIVIG administration had no survival benefit in iGAS patients. However, these overall findings should not be extrapolated to streptococcal toxic shock syndrome as the effect of IVIG therapy in this condition remains uncertain. Considering the rarity of iGAS, conducting a randomized controlled trial may be impractical. Therefore, an equivalent or more extensive observational study is warranted to validate these findings.

Neonatal helminth infection and chronic type 2 inflammation promotes immune suppression through FcγRIIb

Abstract Allergic diseases are rising in industrialized countries. This contrasts with rural communities where decreased allergic incidence correlates with increased prevalence of intestinal helminth infections. While helminths and their byproducts can ameliorate allergic inflammation in adult mice with established disease, it remains unknown if early-life exposure can prevent or delay allergic disease onset. We utilized a neonatal infection model with the gastrointestinal helminth Heligmosomoides polygyrusand found that neonatal H. polygyruscolonization results in chronic infection and type 2 inflammation. This study investigates how chronic and systemic type 2 hallmarks IL-4 and IgG1 may be involved in the long-term suppressive mechanisms induced by neonatal helminth colonization. We hypothesize that IL-4-induced upregulation of the sole inhibitory Fc receptor, FcγRIIb, allows for sustained suppression of T cell mediated inflammation by increasing the activation threshold of antigen presenting cells. Increasing this threshold prevents allergen-specific T cells from becoming optimally activated and instead promotes T cell tolerance. In addition to IL-4 increasing expression of FcγRIIb on macrophages, it promotes the production of its ligand IgG1, completing the suppressive circuit. This model predicts that elimination of FcγRIIb and/or IL-4 will result in greater T cell activation and allergic inflammation. Our in vivoand in vitrodata show that FcγRIIb is necessary for reducing allergic airway inflammation and T cell activation after allergen challenge. Taken together, these data support a model in which chronic helminth infection naturally mimics the suppressive effects of intravenous immunoglobulin therapy. Supported by the National Institutes of Health NIAID training grant (Training Program in Immunology; T32-AI07405)

Effect of intravenous immunoglobulin therapy on the prognosis of patients with severe fever with thrombocytopenia syndrome and neurological complications.

Intravenous immunoglobulin (IVIG) has been reported to exert a beneficial effect on severe fever with thrombocytopenia syndrome (SFTS) patients with neurological complications. However, in clinical practice, the standard regime is unclear and there is a lack of evidence from large-scale studies. A single-center retrospective study was conducted to determine the influence of IVIG dosage and duration on SFTS patients with neurological complications. The primary outcome was 28-day mortality, and laboratory parameters before and after IVIG treatment were measured. Survival curves were generated using the Kaplan-Meier method and analyzed with the log-rank test according to the median IVIG dosage and IVIG duration. Besides, multivariate Cox regression analysis was performed to examine the association between the independent factors and 28-day mortality in SFTS patients. Overall, 36 patients (58.06%) survived, while 26 (41.9%) patients died. The median age of the included patients was 70 (55-75) years, and 46.8% (29/62) were male. A significantly higher clinical presentation of dizziness and headache was observed in the survival group. The IVIG duration in the survival group was longer than in the death group (P <0.05). Additionally, the IVIG dosage was higher in the survival group than in the death group, but there was not a statistically significant difference between the two groups (P = 0.066). The mediating effect of IVIG duration was verified through the relationship between IVIG dosage and prognosis using the Sobel test. Univariate analysis revealed that IVIG dosage (HR: 0.98; 95% CI: 0.97-1.00; P = 0.007) and IVIG duration (HR: 0.54; 95% CI: 0.41-0.72; P <0.001) were significantly associated with risk of death. The multivariate analysis generated an adjusted HR value of 0.98 (95% CI: 0.96-1.00; P = 0.012) for IVIG dosage and 0.26 (95% CI: 0.09-0.78; P = 0.016) for dizziness and headache. Prolonged high-dose IVIG is beneficial to the 28-day prognosis in SFTS patients with neurological complications.

Эффективность высокодозовой внутривенной иммуноглобулинотерапии у детей с расстройствами аутистического спектра, ассоциированными с генетическим дефицитом ферментов фолатного цикла

Обоснование. Ранее неоднократно сообщали об эффективности внутривенной иммуноглобулинотерапии у некоторых детей с расстройствами спектра аутизма без уточнения критерия отбора потенциальных ответчиков на иммунотерапию. Цель исследования: оценить эффективность и безопасность высокодозовой иммуноглобулинотерапии при расстройствах аутистического спектра у детей с генетическим дефицитом фолатного цикла. Материалы и методы. Исследуемую группу составили 78 детей в возрасте от 2 до 10 лет, которые принимали в/в иммуноглобулин в дозе 2 г/кг/мес на протяжении 6 месяцев. В контрольную группу вошли дети аналогичного возрастного и гендерного распределения, которые получали лишь немедикаментозную реабилитационную поддержку. Выявляли замены нуклеотидов MTHFR677 С &gt; Т, MTHFR1298 А &gt; С, MTRR A/G и MTR A/G в различных комбинациях методом полимеразной цепной реакции. Динамику психических симптомов оценивали при помощи шкалы Aberrant Behavior Checklist. Результаты и обсуждение. Достигнуто полное устранение фенотипа расстройств аутистического спектра у 21 пациента и выраженная положительная динамика еще у 33 детей исследуемой группы (p &lt; 0,05; Z &lt; Z0,05). Параллельно отмечалась положительная динамика со стороны других клинических проявлений фенотипа дефицита фолатного цикла: PANDAS (у 19 из 21), эпилептического (у 29 из 36) и кишечного (у 49 из 68 детей) синдромов (p &lt; 0,05; Z &lt; Z0,05). Не отмечено положительной динамики со стороны симптомов поражения пирамидных путей (p &gt; 0,05; Z &gt; Z0,05). Отмечено снижение суммарной вирусной нагрузки и повышение количества естественных киллеров в крови (p &lt; 0,05; Z &lt; Z0,05). Почти полное устранение симптомов лейкоэнцефалопатии в исследуемой группе отмечалось у 29 пациентов, а выраженная положительная динамика — еще в 24 случаях (p &lt; 0,05; Z &lt; Z0,05). Выводы. Внутривенный иммуноглобулин оказывает комплексное положительное воздействие на проявления генетического дефицита фолатного цикла, включая расстройства спектра аутизма, экстрапирамидные нарушения, кишечный синдром, эпилептиформную активность мозга, иммунодефицит и лейкоэнцефалопатию.

Re-Presentation to Medical Care Due to Adverse Effects of Intravenous Immunoglobulin Therapy in Pediatric Immune Thrombocytopenia Patients

Background : Immune Thrombocytopenia (ITP) is one of the most common acquired bleeding disorders affecting children, with an incidence rate of approximately 5-10 per 100,000 children per year. Intravenous immunoglobulin (IVIG) is an effective and widely employed frontline therapy for ITP; but is associated with substantial adverse effects, most commonly including headaches (~40%) and nausea/vomiting (5-26%). These may occur immediately following infusion or up to 72 hours later, often resulting in re-presentation to medical care. Additional diagnostic testing is often performed, including computed tomography (CT) imaging of the head, given concern for intracranial hemorrhage in these severely thrombocytopenic patients who have not yet responded to IVIG.Objective : To identify rates of re-presentation to medical care due to IVIG-associated adverse effects within a cohort of treated pediatric ITP patients, and to identify the impact of this re-presentation to care on patient safety, health-related quality of life (HRQoL), and healthcare-related costs.Methods : We completed a retrospective chart review, inclusive of all pediatric ITP patients receiving IVIG therapy at a large pediatric referral center within a 6-year timeframe from 2010 - 2016. Included patients were between the ages of 0 and 18 years, receiving IVIG for the primary indication of ITP at a dose of 1 g/kg/dose, and receiving the commercial IVIG product Gamunex-C® 10% (Grifols). All patients not meeting these criteria were excluded in order to maximize homogeneity of evaluated patients. Pre-medication with acetaminophen and diphenhydramine is the standard of practice for IVIG administration within the institution.Results : Among the 473 ITP patients who received Gamunex-C® at Texas Children's Hospital from 2010 - 2016, 133 (28%) experienced documented headache, nausea/vomiting, or both following IVIG infusion, consistent with published incidences. Among these patients, 101 (76%) sought medical care due to these symptoms. Of the 81 patients who had already been discharged, 54 (67%) re-presented for Urgent or Emergency Care services; while 27 (33%) called for medical advice or to obtain supportive prescriptions. Of the 20 patients remaining hospitalized, 100% presented as calls to the on-call physician, resulting in additional medical evaluation, often including laboratory or imaging evaluation. Among all patients re-presenting to medical care, 60 (59%) underwent additional laboratory testing, and 36 (36%) underwent CT imaging to evaluate for life-threatening intracranial bleeding. No CT evaluations revealed evidence of intracranial bleeding, and for all 101 patients re-presenting to medical care, symptoms fully resolved with supportive management.Conclusions : Nearly 1/3 of treated patients in our cohort experienced headache and/or nausea/vomiting, consistent with published incidences for Gamunex-C®. Of these, 76% sought further medical care. Subsequent medical management ranged from supportive care only (41%) to full evaluation with repeat laboratory studies (59%) + CT imaging in many cases (36%). These findings implicate substantially increased healthcare-related costs in the form of laboratory, CT imaging, and emergency service expenses; as well as increased risk to these patients' health and safety, in the form of additional radiation exposure, infection risk, and potential exposure to unnecessary therapies. Formal evaluation of downstream HRQoL and costs is ongoing. Additionally, we believe that a standardized prophylactic post-medication strategy could prevent or significantly reduce re-presentation to medical care due to IVIG-associated headache and/or nausea/vomiting, thereby improving HRQoL and cost impact in this patient population; and a formal prospective trial of this strategy is planned. [Display omitted] DisclosuresLambert:AstraZeneca: Research Funding; Educational Concepts in Medicine: Honoraria; Novartis: Honoraria. Despotovic:Sanofi: Consultancy; Schell Cooley LLP: Other: Expert witness.

S0810 Dual Biologic Therapy for the Treatment of Severe/Refractory Inflammatory Bowel Disease: Intravenous Immunoglobulin in Combination With Standard Biologic Agents

INTRODUCTION: Despite improved therapeutic options, a subgroup of Inflammatory Bowel Disease (IBD) patients follow a severe/refractory disease trajectory. Intravenous immunoglobulin (IVIG) is a biologic agent, derived from pooled human plasma, used to treat severe inflammation (i.e. vasculitis, dermatomyositis, etc.) which has been explored as a potential therapy for refractory IBD. However, the use of dual biologic therapy, with IVIG and a second standard biologic agent for IBD treatment has not been described. We report our institutional experience with dual biologic therapy; IVIG treatment with standard biologic therapy in refractory IBD. METHODS: We analyzed a prospective registry of consented IBD patients followed at a tertiary-center to identify Crohn’s disease (CD) or Ulcerative Colitis (UC) patients that received IVIG therapy for refractory disease. Patients that received IVIG for other conditions were excluded. Clinic visits, endoscopic reports and medication exposure before and after IVIG were collected. Harvey-Bradshaw index (HBI) for CD and Ulcerative Colitis Activity Index (UCAI) for UC were utilized to assess the disease course. Quality of life was characterized using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). RESULTS: Among 25 IBD patients (median age 43 yrs, median disease duration 14 yrs, CD 20, females 21), 14 received a combination of IVIG with a 2nd biologic agent (Table 1). Among 19 patients who had active disease before IVIG initiation, 6 (31.6%) achieved remission, 5 of them in combination with second biologic agent. The median improvement in HBI score was 2 (0–3) and in UCAI was 6 (2–10), while the median SIBDQ improvement was 2.5 (1–13). In 6 patients, CRP levels normalized. Furthermore, among 17 patients who were on systemic steroids before IVIG, 3 transitioned to topical steroids, 3 reduced the dosage and 2 patients completely tapered off steroids. In addition, 15 patients reported that IVIG therapy was helpful while 9 patients demonstrated marked improvement endoscopically. Finally, regarding side effects, 7 patients reported headache, 2 nausea, 1 emesis, 1 abdominal pain while 1 patient required hospitalization because of hives and shortness of breath after IVIG infusion. CONCLUSION: Dual biologic therapy using IVIG in combination with standard biologic agents is safe and effective in IBD patients with refractory disease. Further investigation is warranted to define the optimal use of IVIG alone or in combination with biologic agents in refractory IBD.Table 1Figure 1.: The effect of IVIG therapy in averages HBI and UCAI scores when used as monotherapy or in combination with another biologic agent.

Clinical Characteristic Analysis of Seven Children With Bickerstaff Brainstem Encephalitis in China.

Objective: To summarize the clinical, electrophysiological, neuroimaging, and immunological characteristics of seven cases of Bickerstaff brainstem encephalitis (BBE) in China and to determine whether certain clinical features suggestive of BBE can facilitate diagnosis and treatment.Patients and Methods: The clinical data of seven BBE patients treated at the Children's Hospital of Fudan University between 2016 and 2019 were retrospectively analyzed. The clinical and laboratory characteristics of the BBE patients were studied.Results: The seven patients in this study included four females and three males, and the median age at diagnosis was 5.3 years (interquartile range: 3.0–7.1 years). All seven patients had an acute onset with a preinfection history. Seven cases of acute extraocular paralysis, ataxia, and an impaired level of consciousness, two cases of tendon hyperreflexia, one case of positive pathology, and five cases of cranial nerve involvement (the facial nerve and oculomotor nerve) were noted. Cerebrospinal fluid (CSF) examination of five patients showed albuminocytologic dissociation. Electromyography (EMG) was used to examine seven patients; the results were normal in four patients, showed axonal involvement in two patients, and showed demyelination in one patient. The head magnetic resonance imaging (MRI) results of all seven patients were normal. Electroencephalogram (EEG) background activity in the five monitored patients was slowed down. Seven patients underwent serum antibody testing, three of whom were positive for anti-GQ1b antibody, while one was positive for anti-GM1 antibody. Three patients received glucocorticoid combined with intravenous immunoglobulin (IVIG) therapy, and four received only IVIG therapy. One patient required a nasal catheter for oxygen during the disease course, and left upper limb muscle dysfunction (grade III muscle strength of the left upper limb) was observed during the 6-month follow-up. The other six patients had a good prognosis and no dysfunction.Conclusion: Our study identified clinical, imaging, and treatment characteristics that may have prognostic value for pediatric BBE. The positive rate of head MRI was low, the positive rate of serum anti-GQ1b ganglioside antibody was low, and the therapeutic effect of IVIG therapy was good.

Effects of intravenous immunoglobulin therapy and Fc gamma receptor polymorphisms on BK virus nephropathy in kidney transplant recipients.

BK virus nephropathy (BKVN) is a major complication in kidney transplant patients. This study aimed to investigate the efficacy of intravenous immunoglobulin (IVIG) therapy against persistent BKVN and to evaluate the association between persistent BKVN and Fc gamma receptor (FcγR) single nucleotide polymorphisms (SNPs). A total of 86 patients out of 279 kidney recipients with BKVN were investigated in a single-center retrospective study. The majority of 86 patients were Hispanic and Asian (69.8% and 17.4%). Patients were treated with adjunctive IVIG or standard therapy (controls). Subgroup analysis was performed between IVIG responders and non-responders. BK virus copy number and serum creatinine (SCr) were measured to evaluate the impact of IVIG. We analyzed the association between the response to IVIG and genotype at FcγR3A (rs396991) and FcγR2A (rs1801274) SNPs. Viral load in IVIG non-responders was significantly higher than in responders at the time of diagnosis (219271.8 vs 29816.3copies/mL, P=.015) and after 6months of IVIG use (12789.5 vs 1369.5copies/mL, P<.001). However, analyses SNP of FcγR2A (OR=0.807, CI=0.435-1.496 P=.495) and FcγR3A (OR=0.997, CI=0.505-1.970, P=.993) SNPs showed no significant differences between the 2 groups. IVIG appears to lower BK DNA viral load significantly in patients with persistent BKVN. However, no associations were identified between BKVN and FcγR2A or FcγR3A SNPs.

Effects of intravenous immunoglobulin therapy on behavior deficits and functions in sepsis model.

BackgroundWe aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with IgA and IgM (IgGAM).MethodsWe divided 48 Wistar albino rats into five groups: control group, sham-operated group (only antibiotic treatment), cecal ligation and puncture (CLP) group (CLP plus antibiotic treatment), IgG group (250 mg/kg IV IgG) and IgGAM group (250 mg/kg IV IgGAM). Intravenous immunoglobulins were given 5 min after the CLP procedure. Experimental animals put into three behavioral tasks 10, 30 and 60 days after the surgery; to evaluate the locomotor activity, an open field test was performed, elevated plus maze test was used to measure anxiety levels, and depressive state was assessed by forced swimming test. The effects of therapy which were acquired from the results of these tests were used to estimate the behavioral changes after CLP.ResultsThe mortality rate of 50% in the septic rats decreased to 30 and 20% with the administration of IgG and IgGAM, respectively. Significant changes on locomotor activity and depressive-like behavior were reported in the sepsis group; on the other hand, the treatment with immunoglobulins reduced the symptoms. Treatment with immunoglobulins attenuated the sepsis-related anxiogenic-like responses. Behavioral alterations returned to normal on day 60 in all groups.ConclusionsSepsis caused deterioration on behavioral parameters. Immunoglobulin treatments alleviated the symptoms of functional disturbances and caused early reversal of behavioral deficits in septic animals.

Amyloid‐β concentration and structure influences the transport and immunomodulatory effects ofIVIG

Intravenous immunoglobulin (IVIG) contains anti-amyloid-β antibodies as well as antibodies providing immunomodulatory effects that may modify chronic inflammation in Alzheimer's disease. Answers to important questions about IVIG transport into the central nervous system and assessments of any impact amyloid-β has on this transport can be provided by in vitro models of the blood-brain barrier. In this study, amyloid-β[1-42] was pre-aggregated into fibrillar or oligomeric structures, and various concentrations were incubated in the brain side of the blood-brain barrier model, followed by IVIG administration in the blood side at the therapeutically relevant concentrations of 5 and 20mg/mL. IVIG accumulated in the brain side at physiologically relevant levels, with amyloid-β pre-incubation increasing IVIG accumulation. The increased transport effect was dependent on amyloid-β structural form, amyloid-β concentration, and IVIG dose. IVIG was found to decrease monocyte chemotactic protein-1 levels 6.5-18% when low amyloid-β levels were present and increase levels 4.2-23% when high amyloid-β levels were present. Therefore, the presence, concentration, and structure of amyloid-β plays an important role in the effect of IVIG therapy in the brain. The mechanisms of action and transport across the blood-brain barrier (BBB) for an Alzheimer's disease therapeutic, intravenous immunoglobulin (IVIG), remain unknown. We investigated the transport of IVIG across endothelial cell BBB monolayers pre-incubated with amyloid-β peptides. We found that the concentration and structure of amyloid-β plays an important role in the effect of IVIG on BBB tightening and cytokine neutralization. (Note: Figure not drawn to scale.).

Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo-controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy.

Severe Dyshidrotic Eczema after Intravenous Immunoglobulin Therapy for Kawasaki Syndrome

Dyshidrotic eczema is one of the rare cutaneous adverse effects of intravenous immunoglobulin therapy, usually seen in adults. We herein report the first pediatric case of severe dyshidrotic eczema occurring after intravenous immunoglobulin therapy for Kawasaki syndrome.

Passive immunotherapy of sepsis with intravenous immune globulin: not all IVIg preparations are created equal

Normal intravenous immunoglobulin (IVIg) preparations are potentially promising drugs for the adjunctive treatment of sepsis as the pool of IgG antibodies neutralizes a wide array of pathogens plus their virulence factors and in addition possesses broad anti-inflammatory and immunomodulating activities. However, several high quality clinical studies have failed to show an effect of IVIg therapy on survival of sepsis patients. The reason behind this lack of success could be that the wrong immunoglobulin preparations have been used so far. We review evidence from experimental sepsis studies proving that licensed IVIg with additionally enhanced antigen-binding polyspecificity have significant beneficial effects in all sepsis models used.

Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: a randomized double-blind placebo-controlled trial

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in treating various autoimmune and systemic inflammatory diseases. Here, we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG (drug code GB-0998) for patients with corticosteroid-refractory polymyositis (PM) and dermatomyositis (DM) by means of a randomized, double-blind, placebo-controlled study. We randomly assigned 26 subjects (16 PM and 10 DM) to receive either GB-0998 or placebo. Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint (manual muscle test score) and secondary endpoints (serum creatine kinase level and activities of daily living score). However, significant improvements were also found in the placebo group, and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups. We discuss possible reasons for the absence of a clear intergroup difference in efficacy. Nineteen adverse drug reactions were observed in 11 of 26 subjects (42.3%), of which 2 events (decreased muscle strength and increased serum creatine kinase) were assessed as serious; however, they are previously known events. These results indicate that GB-0998 can be safely used with the same precautions as other current IVIG therapy.

A Severe Form of Churg-Strauss Syndrome Complicated with Acute Cardiac Failure and Rapidly Progressive Peripheral Neuropathy -A Possible Effect of Intravenous Immunoglobulin Therapy

We report a case of Churg-Strauss syndrome (CSS) complicated by severe cardiac failure and peripheral neuropathy. Two courses of methylprednisolone pulse therapy were unable to control the disease activity. Repeated intravenous administration of high-dose human immunoglobulin (IVIg) was added together with intravenous cyclophosphamide pulse therapy (IVCY), and the patient's cardiac function and neurological symptoms were gradually ameliorated without any adverse event. Although glucocorticoid and cyclophosphamide comprise the standard therapy for patients with CSS, a number of patients with severe complications appear to be resistant to such conventional treatment. IVIg is thought to be an effective therapeutic option for such patients.

Effectiveness of intravenous immunoglobulin therapy in treating unexplained recurrent spontaneous abortion and its effect on the level of serum soluble human leucocyte antigen G

To explore the effectiveness of intravenous immunoglobulin (IVIG) in treating patients with unexplained recurrent spontaneous abortion (URSA) and the effect of IVIG on the level of soluble human leucocyte antigen G (sHLA-G). This prospective trial conducted at PUMC Hospital between 2004 and 2008 included 60 women with URSA. The patients were allocated into IVIG group (30 cases) and control group (30 cases). IVIG was intravenously used before conception at a dose of 0.2g/kg; once pregnancy was confirmed,IVIG was continued every 4 weeks till the 20th gestational week. Traditional Chinese medicine or/and progesterone were used in control group. The outcome of pregnancy was evaluated by live birth rate and effective rate(defined as the embryo living 4 week longer than previous pregnancy). Serum samples were collected randomly before pregnancy and in the 6th-8th gestational week from IVIG group (15 samples),control group (15 samples),and healthy women (20 samples). The levels of sHLA-G,interferon γ (IFN-γ), interleukin-2 (IL-2), and interleukin-10 (IL-10) were determined by enzyme-linked immunosorbant assay (ELISA). The pregnancy rate was 93.3% in IVIG group. The live birth rate and effective rate were 85.7% (24/28) and 92.9% (26/28) in IVIG group,which were significantly higher than those in control group [56.7% (17/30) (P=0.021) and 63.3% (19/30) (P=0.011)]. Emesis occurred in one woman (3.3%) in IVIG group had during IVIG infusion but was relieved by lowering the speed of infusion. The mean sHLA-G level was (61.37∓35.57) U/ml in control group and (62.70∓37.24) U/ml in IVIG group (P>0.05); both of them were significantly lower than that of healthy women (88.49∓25.37) U/ml (Pü0.05). After pregnancy was achieved, the levels of sHLA-G and IL-10 were (34.19∓14.21) U/ml and (11.71∓2.75) pg/ml, respectively in the IVIG group, which were significantly higher than those in control group [(23.71∓12.83) U/ml and (8.71∓3.01) pg/ml, respectively] (P=0.008). Low-dose IVIG before and after pregnancy is a safe and effective in treating URSA. IVIG improves the development of fetus by up-regulating sHLA-G and IL-10 levels.

S1224 Variability of Anti- C. difficile Toxin Antibody Titers in Commercially-Available IVIG Preparations May Impact Treatment Efficacy

Background: Intravenous immunoglobulin (IVIG) has been used for many years as an adjunct to treat severe and recurrent Clostridium difficile infection. The concentration of serum antibodies to toxins A and B have been shown to correlate with an asymptomatic carrier state in patients with C. difficile colonization. Furthermore, the lack of development of an effective humoral response to C. difficile toxins may result in increased risk of development of recurrent infection. Objective: Studies of IVIG treatment for C. difficile infection have been inconclusive. We therefore sought to examine whether the effectiveness of IVIG therapy could be altered by variability in anti-toxin antibody content in commercial preparations of IVIG. Methods: Antibodies against C. difficile toxins A and B were measured by ELISA in eight commercially-available immunoglobulin preparations. These preparations represent those that are commonly available for IVIG therapy and included two products that have high titers of antibodies against cytomegalovirus (CMV) and respiratory syncytial virus (RSV). Results: Different preparations of IVIG demonstrated approximately a fourfold variability in antibody content against toxin A and toxin B. Preparations that are formulated to contain high-titers of antibodies against CMV and RSV did not contain higher titers of antibody against C. difficle toxins over standard IVIG preparations. Conclusions: Currently-utilized preparations of immunoglobulin, used as IVIG in the treatment of C. difficile colitis show substantial variability in their anti-C. difficile toxin A and B titers. The ability of these preparations to neutralize toxin effect may be affected by anti-toxin titers and this variability may contribute to variations in the published literature with regard to efficacy of IVIG in severe and recurrent C. difficile colitis.

S1226 Does Therapy for Clostridium difficile Positive Without Localizing Features in an ICU Have an Impact on Patient Outcomes?

Background: Intravenous immunoglobulin (IVIG) has been used for many years as an adjunct to treat severe and recurrent Clostridium difficile infection. The concentration of serum antibodies to toxins A and B have been shown to correlate with an asymptomatic carrier state in patients with C. difficile colonization. Furthermore, the lack of development of an effective humoral response to C. difficile toxins may result in increased risk of development of recurrent infection. Objective: Studies of IVIG treatment for C. difficile infection have been inconclusive. We therefore sought to examine whether the effectiveness of IVIG therapy could be altered by variability in anti-toxin antibody content in commercial preparations of IVIG. Methods: Antibodies against C. difficile toxins A and B were measured by ELISA in eight commercially-available immunoglobulin preparations. These preparations represent those that are commonly available for IVIG therapy and included two products that have high titers of antibodies against cytomegalovirus (CMV) and respiratory syncytial virus (RSV). Results: Different preparations of IVIG demonstrated approximately a fourfold variability in antibody content against toxin A and toxin B. Preparations that are formulated to contain high-titers of antibodies against CMV and RSV did not contain higher titers of antibody against C. difficle toxins over standard IVIG preparations. Conclusions: Currently-utilized preparations of immunoglobulin, used as IVIG in the treatment of C. difficile colitis show substantial variability in their anti-C. difficile toxin A and B titers. The ability of these preparations to neutralize toxin effect may be affected by anti-toxin titers and this variability may contribute to variations in the published literature with regard to efficacy of IVIG in severe and recurrent C. difficile colitis.

Effects of intravenous immunoglobulin therapy on patients of guillain barré syndrome in intensive care unit of BSMMU - a retrospective study

Acute polyneuropathy or Guillain Barré syndrome (GBS) following respiratory, gastrointestinal and other illness cause a world wide morbidity and mortality. Immunotherapy (IgG) is early phase of GBS is supposed to reduce life threatening complications. In our retrospective study in ICU, BSMMU Dhaka from January 2007 to December 2008, we included 43 patients admitted during that time. Among the patients 15 patients who received IgG therapy, 1 (one) patient died and 8 patients died among 28 who did not receive Immunotherapy. Recovery rate was 91.66% among IgG group and 66.67% in non IgG group. Ventilated Patients were 53.33% in IgG group and 71.43% patients were in non IgG group. The average duration of stay was 35 days in IgG group and 39.18 days in non-IgG group. The average duration of stay was 22.57 days in IgG group who received immunotherapy in 0-4 days of onset of symptoms and 45.88 days in who got immunotherapy in 5-8 days of onset of symptoms. It is clearly evident that IgG therapy in early phase of GBS reduces, morality, morbidity and duration of hospital (ICU) stay and IgG therapy in early phase of GBS is a better treatment option. Key Words: GBS, immunoglobulin. Journal of BSA, 2008; 21(2): 72-75

Effect of Intravenous Immunoglobulin Therapy on Serum Levels of IgG1 and IgG4 Antidesmoglein 1 and Antidesmoglein 3 Antibodies in Pemphigus Vulgaris

Intravenous immunoglobulin rapidly decreases serum levels of intercellular antibodies in patients with pemphigus vulgaris. However, little is known about the effects of this therapy on antibodies directed specifically against desmoglein 1 and desmoglein 3 and on the IgG subclasses of these antibodies. This study was conducted to study the effect of intravenous immunoglobulin therapy on serum levels of IgG1 and IgG4 antibodies against desmoglein 1 and desmoglein 3 in patients with pemphigus vulgaris. Within 6 to 16 days after initiating a single cycle of intravenous immunoglobulin therapy in 9 patients, a significant decrease in serum levels of IgG4 and IgG1 antibodies against desmoglein 1 and desmoglein 3 occurred in 60% to 100% of the patients, depending on the antibody subclass and specificity. The median decrease in the antibody levels ranged from 34% to 80%. In addition, most patients (n = 6) showed clinical improvement. The decrease in IgG4 antidesmoglein 3 levels seemed to correlate with improvement in disease activity. Intravenous immunoglobulin therapy rapidly lowers serum levels of IgG1 and IgG4 antidesmoglein 1 and desmoglein 3 antibodies. There seems to be a stronger association between the decrease in IgG4 antidesmoglein 3 levels and improvement in clinical activity than with changes in the other antibody levels, which suggests that IgG4 antibodies have a more important role in mediating pemphigus vulgaris.