Intravenous Immunoglobulin Treatment In Patients Research Articles

Population Pharmacokinetic Modelling of Intravenous Immunoglobulin Treatment in Patients with Guillain-Barré Syndrome.

Background and ObjectiveIntravenous immunoglobulin (IVIg) at a standard dosage is the treatment of choice for Guillain–Barré syndrome. The pharmacokinetics, however, is highly variable between patients, and a rapid clearance of IVIg is associated with poor recovery. We aimed to develop a model to predict the pharmacokinetics of a standard 5-day IVIg course (0.4 g/kg/day) in patients with Guillain–Barré syndrome.MethodsNon-linear mixed-effects modelling software (NONMEM®) was used to construct a pharmacokinetic model based on a model-building cohort of 177 patients with Guillain–Barré syndrome, with a total of 589 sequential serum samples tested for total immunoglobulin G (IgG) levels, and evaluated on an independent validation cohort that consisted of 177 patients with Guillain–Barré syndrome with 689 sequential serum samples.ResultsThe final two-compartment model accurately described the daily increment in serum IgG levels during a standard IVIg course; the initial rapid fall and then a gradual decline to steady-state levels thereafter. The covariates that increased IgG clearance were a more severe disease (as indicated by the Guillain–Barré syndrome disability score) and concomitant methylprednisolone treatment. When the current dosing regimen was simulated, the percentage of patients who reached a target ∆IgG > 7.3 g/L at 2 weeks decreased from 74% in mildly affected patients to only 33% in the most severely affected and mechanically ventilated patients (Guillain–Barré syndrome disability score of 5).ConclusionsThis is the first population-pharmacokinetic model for standard IVIg treatment in Guillain–Barré syndrome. The model provides a new tool to predict the pharmacokinetics of alternative regimens of IVIg in Guillain–Barré syndrome to design future trials and personalise treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-022-01136-z.

Challenge of hepatitis B testing following intravenous immunoglobulin therapy in patients with autoimmune skindiseases.

Intravenous immunoglobulin (IVIg) contains pooled immunoglobulins from the plasma of healthy blood donors. All plasma samples are tested for HIV, hepatitis viruses (A, B, and C), and parvovirus B19. As part of this screening step, nucleic acid amplification technology (NAT) is used and allows the presence of specific antibodies targeting viral structures that are commonly used to test for infection status, such as anti-hepatitis B surface antigen (HBs) or anti-hepatitis B virus core (HBc) antibodies. For this reason, manufacturers point to the possibility of false-positive viral serological test results following IVIg treatment due to the passive transfer of antibodies. IVIg therapy is commonly used to manage patients with severe, treatment-refractory autoimmune skin diseases. The aim of this cohort study was to retrospectively quantify newly-discovered positive serological HBV test results after IVIg treatment in patients with autoimmune skin diseases. Between March 2018 and June 2021, 28 patients with autoimmune skin diseases received IVIg therapy, of whom 17 were longitudinally followed-up. None of the patients had evidence of active HBV infection prior to IVIg therapy. All patients (n=17) had detectable anti-HBs antibodies and 12 patients had anti-HBc antibodies 4 weeks after commencing IVIg treatment. Passive antibody transfer seems the most likely interpretation. Nevertheless, complete serological hepatitis assessment should be performed to exclude a new infection. We recommend hepatitis screening before IVIg therapy to prevent diagnostic confusion which may arise due to passive antibody transfer.

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study

ObjectivesIntravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. MethodsThis retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. ResultsThe study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI –0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = –0.022, 95% CI –0.041 to –0.002, p 0.028). DiscussionIVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation.

Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for immune dysregulation diseases. However, the mechanisms by which it reduces systemic inflammation are not well understood. NK cell cytotoxicity is decreased by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte function, especially in NK cells, is important for resolution of inflammation. Our aim was to identify IVIG-induced changes in a cohort of patients with Kawasaki disease (KD) and those that occur broadly in pediatric patients with various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG infusion Treg cell frequency and the proportion of activated CD25+ immunoregulatory CD56bright NK cells was increased, and multiple lymphocyte subsets showed increased expression of the lymphoid tissue homing receptor CD62L. Importantly, IVIG treatment decreased the frequency of cells expressing the degranulation marker CD107a among cytotoxic CD56dim NK cells, which was reflected in a significant reduction in target cell killing and in decreased production of multiple pro-inflammatory mediators. Interestingly, the activating receptor CD336 was expressed on a higher proportion of CD56bright NK cells after IVIG in both KD and autoimmune/inflammatory patients while other NK receptors were increased differentially in each cohort. In autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a higher percentage of CD56dim NK cells, and in contrast to KD patients, CD107a+ cells were increased in this subset. Furthermore, when PBMCs were stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the CD4+ T cells of KD patients expressed CD25 after IVIG therapy but fewer cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG treatment in patients with immune dysregulation has multiple effects, especially on NK cell subsets and CD4+ T cells, which are compatible with promoting resolution of inflammation. These novel findings provide insight into the immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.

Efficacy of IVIG (intravenous immunoglobulin) for corona virus disease 2019 (COVID-19): A meta-analysis

BackgroundThe benefit of IVIG (Intravenous Immunoglobulin) therapy for COVID-19 remains controversial. We performed a meta-analysis to investigate the efficacy of IVIG treatment in patients with COVID-19. MethodsWe searched articles from Web of Science, PubMed, Embase, the Cochrane Library, MedRxiv between 1 January 2020 and February 17, 2021. We selected randomized clinical trials and observational studies with a control group to assess the efficiency of IVIG in treating patients with COVID-19. Subjects were divided into ‘non-severe’, ‘severe’ and ‘critical’ three subgroups based on the information of the study and the World Health Organization (WHO) definition of severity. We pooled the data of mortality and other outcomes using either a fixed-effect model or a random-effects model. ResultsOur meta-analysis retrieved 4 clinical trials and 3 cohort studies including 825 hospitalized patients. The severity of COVID-19 is associated with the efficiency of IVIG. In critical subgroup, IVIG could reduce the mortality compared with the control group [RR = 0.57 (0.42–0.79, I2 = 025%). But there was no significant difference in the severe or non-severe subgroups. ConclusionIVIG has demonstrated clinical efficacy on critical ill patients with COVID-19. There may be a relationship between the efficacy of IVIG and the COVID-19 disease severity. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients’ population that could benefit from IVIG are warranted in the future.

Chronic low-dose intravenous immunoglobulins as steroid-sparing therapy in myasthenia gravis

Intravenous immunoglobulin (IVIg) has been proven beneficial in myasthenic crisis, but their role as maintenance therapy is unclear. The aim of this study was to determine if maintenance therapy with low-dose IVIg improves clinical outcome and may be used as a steroid-sparing agent in myasthenia gravis (MG). We retrospectively reviewed charts of all MG patients treated with IVIg from January 2006 to December 2019. Long-term treatment response to IVIg was assessed by improvement in the Myasthenia Gravis Foundation of America (MGFA) clinical classification scale as primary end point, as well as the ability to reduce the time-weighted average required dose of prednisone as secondary end-point, in a follow-up period of 36months. 109 patients were treated with IVIg. The mean follow-up time was 34.03 ± 5.5months. Sixty-seven patients (61.4%) responded to therapy with at least one-point improvement of the MGFA scale. There was no statistical difference in demographic and clinical characteristics between IVIg responders and non-responders. The mean prednisone dose decreased significantly from 33.1 ± 14.5mg at baseline to 7.2 ± 7.8mg after 36months of IVIg treatment (P < 0.0001), with the greatest effect after 6months (33.1 ± 14.5mg Vs. 17.9 ± 11.7mg; P < 0.0001). In the follow-up period of 36months, most patients (92.5%) remained clinically and pharmacologically stable under chronic IVIg treatment. This retrospective study demonstrates that chronic low-dose IVIg treatment in patients with MG improves clinical outcomes and has a prolonged and significant steroid-sparing effect over a period of 3years.

The Cost Effectiveness of Immunoglobulin vs. Hematopoietic Stem Cell Transplantation for CIDP.

Background: Intravenous immunoglobulin (IVIG) is effective as standard first line therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but some patients remain dependent on its long-term use. Recently, we have reported that autologous non-myeloablative hematopoietic stem cell transplantation (HSCT) is an effective second line therapy for CIDP.Objectives: To compare the cost of chronic IVIG vs. autologous HSCT (a one-time therapy), we collected data on patients with CIDP undergoing HSCT between 2017 and 2019. This was compared with published literature on the costs and efficacy defined by the Inflammatory Neuropathy Cause And Treatment (INCAT) disability score, Medical Research Council (MRC) sum score, hand grip strength, and SF-36 quality of life (QOL) for CIDP.Methods: Between 2017 and 2019, nineteen patients with chronic CIDP (mean disease treatment duration prior to HSCT of 6 years) underwent autologous HSCT with mean cost of $108,577 per patient (range $56,327–277,119, standard deviation $53,092). After HSCT, 80% of patients remain IVIG and immune treatment free for up to 5 years. In comparison, published cost of IVIG treatment in the USA for an average CIDP patient exceeds $136,000 per year. Despite remaining treatment free, HSCT demonstrated greater improvement in efficacy compared to immunoglobulins.Recommendations: Given the long-term treatment-free remission and better outcome measurements, autologous HSCT is more cost effective than long-term IVIG treatment in patients with chronic CIDP. However, costs will depend on patient selection, the HSCT regimen, and regional variations. Further analysis of the health economics, i.e., cost/outcome ratio, of HSCT as therapy for chronically IVIG dependent CIDP is warranted.

Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy.

ObjectivesNeurofilament light chain (NfL) levels have been suggested as reflecting axonal damage in various inflammatory and neurodegenerative disorders, including acquired peripheral neuropathies. We aimed to investigate if serum NfL (sNfL) levels can be a biomarker of disease activity and treatment response in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).Materials and methodsThe sNfL levels of eleven newly diagnosed patients with CIDP were retrospectively assayed and compared with seven healthy volunteers. The levels were assayed before and after intravenous immunoglobulin treatment in patients with CIDP and were also assayed in the remission period.ResultsBaseline sNfL levels in patients with CIDP before treatment were significantly higher than those in healthy controls. The levels significantly decreased overtime after one month of treatment and in remission period. There were significant negative correlations between the sNfL levels and the disease duration (the interval between the onset of the disease and the time of sampling), and weak correlations between the sNfL levels and overall neuropathy limitations scale.ConclusionssNfL may be a potential biomarker reflecting the disease activity in patients with CIDP.

Successful treatment of human immunodeficiency virus-associated highly active antiretroviral therapy-resistant vacuolar myelopathy with intravenous immunoglobulin

For the first time, human immunodeficiency virus (HIV)-associated vacuolar myelopathy (VM) was detailed in an autopsy-based study of 89 cases in 1985. This condition is the most common cause for spinal cord lesions in HIV patients. VM's pathogenic mechanism remains unclear; however, it is assumed that the disease can be related to both, the direct neurotoxic impact of the HIV and HIV-induced activation of immunopathological processes in the central nervous system (CNS). Reviewed in this paper is a case where the VM presentation deteriorated drastically when treated with highly active antiretroviral therapy, and almost completely regressed after the patient received the intravenous immunoglobulin (IVIg) treatment. The considered case demonstrates the viability of IVIg treatment in patients with HIV-associated CNS pathology, particularly when autoimmune reactions are suspected. The results of placebo-controlled studies of IVIg in patients with HIV-associated myelopathy may give a reliable evaluation of IVIg use in this context.

EVALUATION OF A MOTOR AND SENSORY DISTURBANCE QUESTIONNAIRE FOR PATIENTS WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

It is difficult to evaluate neurological signs of multiple mononeuritis (MM) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We created a new questionnaire about motor and sensory disturbances in EGPA and investigated whether the questionnaire would be a useful tool in the management of MM in EGPA patients. We classified 40 EGPA patients attending Hiratsuka City Hospital into two groups, namely 30 who were treated with intravenous immunoglobulin (IVIG) and 10 who achieved remission by conventional treatment without IVIG. We created a questionnaire for the evaluation of motor and sensory disturbance in EGPA (ANCA related.com). In patients who received IVIG, we evaluated motor and sensory disturbance scores at disease onset, before IVIG, 1 week and 1 month after the end of IVIG. In patients treated without IVIG, we evaluated these scores at disease onset and at the time of the latest examination. The total motor disturbance score at disease onset was significantly lower in EGPA patients who received IVIG than in those who did not receive it. Disease duration was significantly inversely correlated with the change in the sensory disturbance ratio, but not with the motor disturbance ratio. The motor disturbance ratio was significantly correlated with the manual muscle test improvement ratio. In patients who received IVIG, the total motor disturbance score increased significantly, and the total sensory disturbance score decreased significantly, 1 month after IVIG. By using the questionnaire we could evaluate changes in motor and sensory disturbance after IVIG treatment in patients with EGPA. The questionnaire should be useful in the management of MM in EGPA patients.

Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection

IntroductionKawasaki disease (KD) can be associated with concomitant viral or bacterial infections. Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. Although concomitant infection does not affect coronary outcome, it is unknown how it influences the response to IVIG treatment.MethodologyRetrospective cohort study between 2008 and 2016 in a tertiary pediatric university hospital, including 154 children, of which 59 (38%) had concomitant infection.ResultsChildren with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p = 0.04), and 48 hours after IVIG administration (111 vs 59 mg/L, p = 0.003). Nevertheless, there was no statistically significant difference in the prevalence of coronary complications (Z-score > 2.5) between children with and without concomitant infection (36% vs 39%, p = 0.68).ConclusionChildren with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment. This association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication. Accordingly, prospective studies to distinguish true IVIG resistance from infection induced persistent fever is warranted.

Mycoplasma Infection as a cause of Persistent Fever after Intravenous Immunoglobulin Treatment of Patients with Kawasaki Disease: Frequency and Clinical Impact.

BackgroundMycoplasma is a common cause of respiratory infections and may require differential diagnosis from Kawasaki disease (KD). In this study, we investigated the frequency and clinical manifestations of mycoplasma infection in patients with KD.Materials and MethodsMedical records of 375 in-patients admitted for treatment during the acute stage of KD, were collected, and reviewed retrospectively. Of these patients, 152 (40.5%) were also tested for recent mycoplasma infection. Patients with positive results (anti-mycoplasma IgM Ab >1:640 or cold agglutinin >1:64) were designated as the case group (n = 37, 24.3%) whereas those with negative results were designated as the control group (n = 115, 75.7%). Clinical findings of the two groups were compared.ResultsPatients in the case group were older than those in the control group (mean age, 48.2 ± 32.1 months, vs. 31.7 ± 21.7 months; P = 0.001). There were significant differences between the case and control groups in the changes in the extremities (78.3% vs. 57.4%, respectively; P = 0.031), and in fever duration (6.5 ± 2.5 days vs. 5.4 ± 1.5 days; P = 0.047). Of the 37 patients with positive mycoplasma testing, 7 (18.9%) had persistent fever even after the symptoms and signs of systemic inflammation (acute phase of KD) had been resolved. These patients were positive for mycoplasma infection during further evaluation of persistent fever, and all of them responded to macrolide antibiotics.ConclusionsWe found that mycoplasma infection is somewhat related to KD. When fever persists after resolution of the acute stage of KD, mycoplasma infection may be considered as a possible cause of fever in preschool-aged children.

Meta-analysis of factors predicting resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease.

PurposeStudies have been conducted to identify predictive factors of resistance to intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). However, the results are conflicting. This study aimed to identify laboratory factors predictive of resistance to high-dose IVIG for KD by performing meta-analysis of available studies using statistical techniques.MethodsAll relevant scientific publications from 2006 to 2014 were identified through PubMed searches. For studies in English on KD and IVIG resistance, predictive factors were included. A meta-analysis was performed that calculated the effect size of various laboratory parameters as predictive factors for IVIG-resistant KD.ResultsTwelve studies comprising 2,745 patients were included. Meta-analysis demonstrated significant effect sizes for several laboratory parameters: polymorphonuclear leukocytes (PMNs) 0.698 (95% confidence interval [CI], 0.469–0.926), C-reactive protein (CRP) 0.375 (95% CI, 0.086–0.663), pro-brain natriuretic peptide (pro-BNP) 0.561 (95% CI, 0.261–0.861), total bilirubin 0.859 (95% CI, 0.582–1.136), alanine aminotransferase (AST) 0.503 (95% CI, 0.313–0.693), aspartate aminotransferase (ALT) 0.436 (95% CI, 0.275–0.597), albumin 0.427 (95% CI, –0.657 to –0.198), and sodium 0.604 (95% CI, –0.839 to –0.370). Particularly, total bilirubin, PMN, sodium, pro-BNP, and AST, in descending numerical order, demonstrated more than a medium effect size.ConclusionBased on the results of this study, laboratory predictive factors for IVIG-resistant KD included higher total bilirubin, PMN, pro-BNP, AST, ALT, and CRP, and lower sodium and albumin. The presence of several of these predictive factors should alert clinicians to the increased likelihood that the patient may not respond adequately to initial IVIG therapy.

Prediction of unresponsiveness to second intravenous immunoglobulin treatment in patients with Kawasaki disease refractory to initial treatment.

PurposeThis study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD).MethodsThis was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses.ResultsEighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216–3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028–0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL.ConclusionThe serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.

Abstract 96: Changes In HDL Cholesterol During The Acute Phase of Kawasaki Disease

To determine the correlations between changes in high-density lipoprotein cholesterol (HDL-C) and other blood variables during the acute phase of Kawasaki disease (KD), we investigated changes in the plasma level of HDL-C, serum apolipoproteins and number of peripheral blood monocytes. 26 Japanese patients with KD were subjects of this study. Plasma HDL-C decreased during the 1st week of illness, and increased during the 2nd week. The mean levels of minimum HDL-C in KD patients treated with total intravenous immunoglobulin (IVIG) dose ≧ 4g/kg, was significantly lower than those treated with total IVIG dose &lt; 4g/kg (p=0.0005). There was a strong direct correlation between minimum HDL-C in KD patients and HDL-C on 5th day of KD onset (r=0.71, p &lt; 0.0001). Assessing the performance of plasma HDL-C on 5th day of KD onset in predicting the necessity for high-dose IVIG treatment to KD, ROCs were plotted and the AUC was 0.82. A cutoff value of 16mg/dl had a specificity of 0.82 and sensitivity of 0.80 for predicting those. The apo A-I and A-II levels were correlated with plasma HDL-C, respectively. And the peripheral blood monocytes counts which correlated with serum levels of macrophage-colony stimulating factor, were not correlated with plasma HDL-C. Plasma HDL-C levels during the 1st week of illness might serve as a predictor for non-responder to low-dose IVIG treatment in patients with acute KD.

Sialylated IgG-Fc: a novel biomarker of chronic inflammatory demyelinating polyneuropathy

ObjectiveSialylation in Fc portion of IgG plays a crucial role in the pathogenesis of autoimmune diseases and the working mechanism of intravenous immunoglobulin (IVIG). We aim to test whether IgG-Fc...

Intravenous immunoglobulin and immune response.

Intravenous immunoglobulin and immune response.

Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21(low) B cells.

Intravenous immunoglobulin (IVIG), besides its use as replacement therapy in patients with antibody deficiencies, is broadly used as an immunomodulatory agent for the treatment of autoimmune and inflammatory disorders. The mechanisms of action of IVIG include Fc receptor blockade, inhibition of cytokines and growth factors, modulation of macrophages and dendritic cells, enhancement of regulatory T cells, and modulation of B cells through the FcγRIIB receptor and CD22. Recent studies suggest that in vitro exposure of human B cells to IVIG determines functional changes reminiscent of anergy and that IVIG treatment of patients with common variable immunodeficiency (CVID) induces in B cells ERK activation, a feature of anergy. Here, we show that IVIG therapy drives the B cells of patients with CVID to down-regulate CD21 expression and to assume the peculiar phenotype of the anergic-like, apoptosis-prone CD21(low) B cells that are spontaneously expanded in a subset of CVID and in some other immunological disorders. The CD21(low) B cells newly generated after IVIG infusion undergo spontaneous apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed by a significant, although discrete, decrease in the number of circulating B cells, but not of T cells or of natural killer cells. These findings suggest that IVIG therapy may constrain antibody responses by inducing B cell depletion through differentiation into CD21(low) B cells that undergo accelerated apoptosis.

IL-31 associated with coronary artery lesion formation in Kawasaki disease.

BackgroundKawasaki disease (KD) is known to be associated with T help (Th) 2 reaction and subsequently allergic diseases. Interleukin-31 (IL-31) has also been reported to be involved in Th2 mediated diseases such as allergic diseases. However, the role of IL-31 in KD has not been previously reported. The aim of this study is to investigate whether IL-31 is associated with KD and its clinical outcome.MaterialA total of 78 KD patients who met the criteria of KD were enrolled in this study as well as 20 age-matched controls. Plasma samples were conducted to measure IL-31 before intravenous immunoglobulin (IVIG) treatment (KD1), within 3 days after IVIG treatment (KD2) and at least 3 weeks after IVIG treatment (KD3) by utilizing enzyme-linked immunosorbent assay (ELISA).ResultOur findings showed that IL-31 expression was higher in KD patients after IVIG treatment significantly (KD2>KD1: 1265.0±199.3 vs. 840.2±152.5 pg/ml, p<0.0001). Further analysis revealed that IL-31 level was significantly higher in KD patients with coronary artery lesion (CAL) (656.6±139.5 vs. 1373.0±422.0 pg/ml, p = 0.04) before IVIG treatment (KD1). There were no significant differences between the IVIG resistance and IVIG responsiveness groups.ConclusionIL-31 was increased after IVIG treatment in patients with KD and was significantly associated with CAL formation. The results from this study may help to identify a novel risk factor for predicting KD and CAL formation.

Intravenous immunoglobulin treatment of patients with recurrent miscarriage

Introduction: Implantation rates per transferred embryo after IVF/ICSI still stagnate in Europe at around 20% while decreasing to 5% for patients with repeated previous embryo implantation failures (RIF patients). Identification of local immune mechanisms inducing RIF may allow IVF treatment to be personalized to counteract the documented deleterious endometrial mechanism. Design: Prospective observational cohort study of 287 RIF patients. An endometrial immune uterine check-up is performed during the middle luteal phase of a nonconceptual cycle. In the case of documented poor or over-endometrial immune activation, personalized strategies were recommended. The outcome is the ongoing pregnancy rate occurring after the first embryo transfer following the evaluation. Materials andmethods: The endometrial biopsy is performed with a Cornier pipelle. After histological dating, we quantify the mobilization of uterine natural killer cells (uNK) (immunostaining CD56+), the endometrial mRNA expression of IL-15 (reflecting the maturation state of uNK), of IL-18 (reflecting the Th-1/Th-2 balance) and of TWEAK/Fn-14 (reflecting the TNF-related local immuneregulation) by real-time PCR. Such procedures lead to documentation of either low local reactivity, suggesting a problem of adhesion, or the opposite, an over-immune local activation suggesting the necessity of simultaneous local control to avoid embryo rejection (EP 12177377.42404). Normal ranges were predetermined in fertile controls. Results: 26.5% (76/287) and 58.5% (168/287) of the RIF patients showed endometrial profiles of low or the opposite over-immune activation respectively, while only 15% (43/287) had a profile comparable to fertile controls. Consequently, specific recommendations either to promote the adhesion (local injury, low stimulation, sexual intercourse, supplementationwith luteal HCG) or to control the endometrial activation (no local injury, supplementation with corticosteroids and a high dose of progesterone) were applied. Ongoing pregnancy rates observed after the first embryo transfer were 53.9% (41/76), 40% (67/168), and 9% (4/43) according to their immune profiles of low, overor normal endometrial activation (p<0.001). Conclusion: Immune uterine deregulation was observed in 85%. Optimization of uterine receptivity allowed the unexpected PR to be reached at 44%. In contrast, in the group with no deregulation diagnosed, the ongoing PR was significantly lower, most probably explained by unresolved problems with gametes.