Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Acute Acquired Immune Thrombocytopenia After Cardiac Surgery: A Challenging Case

Thrombocytopenia is a common condition that recognizes an infinite number of possible causes, especially in specific settings like the one covered in this case report: the postoperative period of cardiac surgery. We report a case of an old male with multiple comorbidities who underwent a coronary angioplasty procedure and aortic valve replacement. He showed severe thrombocytopenia in the postoperative days. Differential diagnosis required a big effort, also for the experts in the field. Our goal was to aggressively treat the patient with prednisolone, platelets, and intravenous immunoglobulins to maximize the prognosis. Our patient developed no complications and was discharged successfully

Advances in predictive scoring system for intravenous immunoglobulin non-responsive Kawasaki disease / 国际儿科学杂志

Intravenous immunoglobulin(IVIG)is internationally recognized as the main treatment for Kawasaki disease(KD)in the acute phase, and its application can effectively reduce the incidence of coronary artery disease(CAL).However, in clinical practice, up to 26.8% of KD children do not respond to IVIG treatment, and their risk of CAL is higher and the degree of CAL is more severe.Early adjustment of treatment, such as early combined use of glucocorticoids, may play an important role in improving the prognosis and shortening the course of IVIG non-responsive KD.Therefore, early identification of IVIG non-response KD is of great significance to clinicians.In the past 20 years, domestic and foreign scholars have successively established predictive scoring system to predict the possibility of IVIG non-response in children with KD and optimize the early treatment.This article reviews the domestic and foreign research on the score system for predicting IVIG non-response in KD, in order to provide reference for clinical diagnosis and treatment.

Effect of IgG dimer concentration on the binding ability of IgG Fc fragment in IVIG to THP-1 cell surface receptors / 中国输血杂志

【Objective】 To investigate the effect of immunoglobulin G (IgG) dimer concentration of intravenous immunoglobulin (IVIG) on the binding ability of IgG Fc fragment to THP-1 cell surface receptors. 【Methods】 Firstly, protein purification and high performance liquid chromatography (HPLC) were used to prepare different concentrations of IgG dimers. After that, IgG dimer was added to IVIG to prepare IVIG containing different concentrations of IgG dimer. Finally, based on the method established in our laboratory, we analyzed the effect of IgG dimer concentration in IVIG on the binding ability of IgG Fc fragment to THP-1 cell surface receptors. 【Results】 When the concentration of IgG dimer in IVIG was 1.11%-10.30%, its binding ability to Fc receptors on the surface of THP-1 cell was 97.67%-135.33%, and this binding ability was positively correlated with the concentration of IgG dimer. When the IgG dimer concentration exceeded 13.22%, the binding ability had no correlation with the IgG dimer concentration. 【Conclusion】 A certain concentration of IgG dimer can promote the binding ability of the IgG Fc fragment in IVIG to receptors on the surface of THP-1 cells, which needs further verification from animal experiments and clinical data.

Diversity of IgG autoantibodies of 4 Chinese intravenous immunoglobulins / 中国输血杂志

【Objective】 To develop methods to display the IgG autoantibody repertoire of intravenous immunoglobulin (IVIG) products, analyze the different types of antibodies and study the diversity of IgG autoantibody in 4 IVIG preparations from different Chinese manufacturers. 【Methods】 Two-dimensional gel electrophoresis and immunoblotting with human umbilical vein endothelial cell (HUVEC) proteins were used to demonstrate the IgG autoantibody repertoire and the human protein microarray with bioinformatics analysis was employed to profile the immune reactive autoantigens of the 4 IVIG preparations. 【Results】 The methods to showcase the autoantibody repertoire and study the antibody diversity of IVIG were successfully established. High-quality repertoires of IVIG autoantibodies and biological information about self-proteins that can be recognized were obtained. There was a significant difference in the recognition of the quantity and variety of the self-antigens by different IVIG products. The number of antibodies against HUVEC proteins in four products ranged from 241-386. The number of proteins recognized on the human protein chip ranged from 292-435, with 172 human self-proteins recognized by all four products. 【Conclusion】 Demonstration of antibody repertoire and protein chip technology can be used to analyze IVIG products′ IgG autoantibody repertoire. All four preparations tested in this study exhibited a broad spectrum of antibodies against HUVEC proteins and human proteome microarray, each product had its unique antibody repertoire characteristics.

Initial Immunomodulation and Outcome of Children with Multisystem Inflammatory Syndrome Related to COVID-19: A Multisite Study from India

Objective To determine the outcomes in children with MIS-C receiving diferent immunomodulatory treatment. Methods In this multicentric, retrospective cohort study, data regarding treatment and outcomes of children meeting the WHO case defnition for MIS-C, were collected. The primary composite outcome was the requirement of vasoactive/inotropic support on day 2 or beyond or need of mechanical ventilation on day 2 or beyond after initiation of immunomodulatory treatment or death during hospitalization in the treatment groups. Logistic regression and propensity score matching analyses were used to compare the outcomes in diferent treatment arms based on the initial immunomodulation, i.e., IVIG alone, IVIG plus steroids, and steroids alone. Results The data of 368 children (diagnosed between April 2020 and June 2021) meeting the WHO case defnition for MIS-C, were analyzed. Of the 368 subjects, 28 received IVIG alone, 82 received steroids alone, 237 received IVIG and steroids, and 21 did not receive any immunomodulation. One hundred ffty-six (42.39%) children had the primary outcome. On logistic regression analysis, the treatment group was not associated with the primary outcome; only the children with shock at diagnosis had higher odds for the occurrence of the outcome [OR (95% CI): 11.4 (5.19–25.0), p<0.001]. On propensity score matching analysis, the primary outcome was comparable in steroid (n=45), and IVIG plus steroid (n=84) groups (p=0.515). Conclusion While no signifcant diference was observed in the frequency of occurrence of the primary outcome in diferent treatment groups, data from adequately powered RCTs are required for defnitive recommendations.

An Observational Study of Clinical Profile & Short-Term Outcome with Use of Pulse Therapy of Methylprednisolone Alone Vs Methylprednisolone and Intravenous Immunoglobulin In Multisystem Inflammatory Syndrome In Children

Background: Multisystem inflammatory syndrome in children (MIS-C) is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. There is persistent fever along with inflammation, which can lead to medical emergencies and neonates and children may require critical care. Aims and objectives: This study evaluates use of pulse therapy of methyl prednisolone versus prednisolone and intravenous immunoglobulin (IVIG) in multisystem inflammatory syndrome in children (MISC). Methodology: This analytical study was carried out in 30 children with history of SARS-CoV-19 or MISC attending the PICU or NICU of the Tertiary care centre of DVVPF's Medical College, Ahmednagar. The study was carried out from January 2021 to December 2021.Results: Total of 30 patients were studied with male majority (60%), and mean age of 7.35 years. 28 were kept in the ICU (93.33%). GI symptoms were seen in 24 cases (80%), Mucocutaneous manifestation in 25 cases (83.33%), Multiorgan involvement (>3 organs) in 23 cases (76.67%). D Dimer was raised in 29 cases (96.67%), Thrombocytopenia was seen in 24 cases (80%). CNS involvement in 14 cases (46.67%) with headaches in 7 (23.33%), encephalopathy in 5 cases (16.67%) and seizures in 4 cases (13.33%). Respiratory system involvement was seen in 16 cases (53.33%). We observed that the outcome characteristic features were better in the Methylprednisolone pulse therapy plus IVIG group. (p<0.05) Out of 15 patients in the two groups, 3 patients died in Methylprednisolone pulse therapy group (20%) while there was one death in the Methylprednisolone pulse therapy plus IVIG group. Significant difference was seen in the survival of the two groups. (p = 0.04). Conclusion: There is improvement in both the groups which received the treatment with either Methylprednisolone pulse therapy or Methylprednisolone pulse therapy plus IVIG. Comparatively there was less ICU stay, less complications and better patient survival in Methylprednisolone pulse therapy plus IVIG group.

Technical specification for clinical diagnosis and treatment of human parvovirus B19 infection in kidney transplant recipients (2022 edition) / 器官移植

Long-term use of immunosuppressant in kidney transplant recipients leads to poor immune function and infection with various pathogens. In recent years, along with the advancement of detection technique of human parvovirus B19 (HPV-B19) infection and the increasing quantity of kidney transplantation, the infection rate of HPV-B19 after kidney transplantation has been elevated year by year, becoming one of the major causes of pure red cell aplasia (PRCA), affecting the recovery of renal allograft function, and even leading to the injury or poor prognosis of renal allograft. To further standardize the diagnosis and treatment of HPV-B19 infection in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association and National Kidney Transplantation Quality Control Center jointly organized experts to formulate the clinical diagnosis and treatment specification for HPV-B19 infection after kidney transplantation from the perspectives of etiology, epidemiological characteristics, clinical manifestations, diagnosis, prevention, treatment, existing problems and prospects of HPV-B19, aiming to provide guidance for standardized prevention and treatment of HPV-B19 infection post-kidney transplantation in China.

A systematic review and meta-analysis on the safety and efficacy of Second Dose Immunoglobulin versus High Dose Pulse Methylprednisolone in Refractory Kawasaki Disease

Background@#There is limited information available regarding the management of IVIG-refractory Kawasaki Disease (KD). @*Objective@#This study aimed to evaluate the safety and efficacy of a second intravenous immunoglobulin (IVIG) infusion versus intravenous methylprednisolone (IVMP) in patients with IVIG-refractory KD.@*Methodology@#Cochrane Library, PubMed, Medline, Elsevier (Science Direct), Springer Link and BMJ databases were searched from May 1, 2020 to December 31, 2020. We included randomized controlled trials (RCTs) and high-quality prospective and retrospective studies, with population restricted to children 0 months to 18 years, with KD refractory to initial IVIG at 2g/kg, who remained febrile for 24-48 hours after completion of initial IVIG, and who received second-line monotherapy with either a second dose IVIG or IVMP. We conducted a meta-analysis using Review Manager [RevMan] 5.4.1 software.@*Results@#A total of six studies (n=188 patients) were analyzed. The incidence of coronary artery lesions was comparable between a second dose of IVIG and IVMP (RR 0.82, 0.34-1.96, P=0.66) in patients with IVIG-refractory KD. The rate of fever resolution to a second IVIG, compared to IVMP, was not significantly different between groups (RR 0.97, 0.84-1.13, P=0.72). There was a significantly higher incidence of adverse events in the IVMP group (RR 0.42, 0.26-0.57, P=0.0002), but these were all transient and resolved without further treatment. @*Conclusion@#There is no significant difference in the incidence of coronary artery lesions and rate of fever resolution post-retreatment with a second dose of IVIG versus IVMP in IVIG-refractory KD. More adverse events were reported in the IVMP group.

Preliminary study on the effect of IVIG with different Aβ antibody on cognitive function of Alzheimer′s disease model mice / 中国输血杂志

【Objective】 To investigate the effect of intravenous immunoglobulin(IVIG) with different Aβ antibody content on the cognitive function of Alzheimer′s disease model mice. 【Methods】 IVIG from 8 domestic blood products companies were selected. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of Aβ40/42 antibody. Three kinds of IVIG with high, middle and low Aβ42/40 antibody levels were selected to treat 3xTg-AD mice. Forty 3-month-old 3xTg-AD mice were randomly divided into 4 groups with 10 mice in each group(half male and half female). Three treat groups were intraperitoneally injected with three kinds of IVIG with 1g·kg-1 for 12 weeks(twice a week). The controls were injected with the same volume of saline. Behavioral tests were performed immediately by using the mouse behavior analysis system after a total of 24 injections. 【Results】 The concentrations of antibodies(μg/mL) against Aβ40 monomer in IVIG ranged 0.7±0.05 to 3.1±0.05, concentrations of antibodies against Aβ40 oligomer ranged 11.7±0.7 to 32.0±2.2, concentrations of antibodies against Aβ42 monomer ranged 1.8±0.1 to 27.9±0.3, and concentrations of antibodies against Aβ42 oligomeric ranged 2.3±0.1 to 49.4±2. High(IVIG-1), medium(IVIG-8) and low(IVIG-6) IVIG were selected for mice study. In the open field test, the time of four groups of mice entering the central area(s) was 0.5±0.9, 23.4±6.1(P<0.0001), 4.6±2.8 and 2.6±2.3, respectively; the number of feces(grains) was 1.6±0.7(P<0.0001), 1.2±0.4(P<0.0001), 2.4±0.5(P<0.001) and 3.8±0.8, respectively. In the novel object recognition test, the scores of exploring new objects were 71.3±29.5(P<0.05), 71.8±20.5(P<0.05), 75.9±26.9(P<0.01) and 25.6±23.7, respectively. In the Barnes maze test, the time of exploring the target hole in the IVIG-8 group was significantly longer than that in the control on the 6th day(50.3±19.3 vs 21±14.6, P<0.05) and the 13th day(58.2±20.9 vs 19.2±15.9, P<0.005), but there was no significant difference between the IVIG-1, 6 groups and the control. 【Conclusion】 There is a significant difference in the level of Aβ40/42 antibody among 8 kinds of domestic IVIG. Domestic IVIG could improve the cognitive function of 3-month-old 3xTg-AD mice after continuous intervention for 3 months. The improvement effect, however, was related to the Aβ antibody in IVIG, but not to the antibody concentration.

Study of the use of IVIG Normal Human Immunoglobulin in the La Samaritana University Hospital during the period of 2017-2019 / Estudio de utilización de Inmunoglobulina Humana Normal IGIV en el Hospital Universitario de la Samaritana durante el periodo de 2017-2019 / Estudo de utilização de Imunoglobulina Humana Intravenosa Inespecífica (IGIV) no Hospital Universitário da Samaritana (HUS) durante o período 2017-2019

SUMMARY Introduction: Non-specific intravenous human immunoglobulin (IVIG) is a valuable therapeutic resource in specific pathologies, however, there are pathological conditions for which there is not yet a defined therapeutic strategy and due to similarity or biological plausibility, some prescribers end up using it. Aim: To identify the indications for which IVIG has been prescribed in the HUS. Methodology: A descriptive observational cross-sectional study was performed with retrospective collection of information between January 1, 2017, and December 31, 2019. Materials and methods: 180 medical records were reviewed, demographic characterization of the study, clinical and pharmacological population of patients who have been prescribed at least one dose of immunoglobulin. In addition, the indications proposed in the clinical history were compared with the indications approved by regulatory authority (Invima). Results: It was determined that the population with the highest predominance to which IVIG was prescribed in the HUS, were women in young adulthood. Likewise, the use of IVIG presented a higher frequency in patients with idiopathic purple thrombocytopenia (ITP), Guillain-Barré Syndrome (GBS), Systemic Lupus Erythematosus (SLE) and neonatal jaundice due to other existing hemolysis specified as main diagnoses. The indications for which there is an Invima approval are nonspecific, which means that there is no defined therapeutic strategy with IVIG and therefore that prescribers for similarity or biological plausibility turn out to be using it, for uses not indicated in the sanitary registry (UNIRS), which represented 71 % of indications for which IVIG was prescribed in HUS. Conclusion: The indications for the most prescription with IVIG were idiopathic purple thrombocytopenia (ITP) and Guillain-Barré syndrome (GBS). The non-prescribed use of IVIG in this study reached a figure of 71%.

RESUMEN Introducción: La inmunoglobulina humana intravenosa inespecífica (IGIV) es un valioso recurso terapéutico en patologías específicas, sin embargo, existen condiciones patológicas para las que aún no existe una estrategia terapéutica definida y por similitud o plausibilidad biológica algunos prescriptores terminan usándola. Objetivo: Identificar las indicaciones para las cuales se ha prescrito inmunoglobulina humana inespecífica intravenosa (IGIV) en el HUS. Metodología: Se realizó un estudio observacional descriptivo de corte transversal con recolección retrospectiva de la información entre enero 1 de 2017 hasta diciembre 31 de 2019. Materiales y métodos: Se revisaron 180 historias clínicas, de pacientes a quienes se les prescribió al menos una dosis de inmunoglobulina, se realizó una caracterización demográfica, clínica y farmacológica de la población estudio. Además, se comparó las indicaciones descritas en la historia clínica con las indicaciones aprobadas por el Invima. Resultados: Se identificó a mujeres adultas jóvenes como población a quienes se le prescribió IGIV con mayor frecuencia. Asimismo, las indicaciones para la que se prescribe IGIV con mayor frecuencia fueron la purpura trombocitopenia idiopática (PTI), síndrome de Guillain-Barré (SGB), lupus eritematoso sistémico (LES) e ictericia neonatal debida a otras hemolisis existentes. Las indicaciones aprobadas por la agencia regulatoria colombiana (Invima) son inespecíficas por lo que el uso de la IGIV es prescrito ya sea por similitud o plausibilidad biológica, lo cual puede explicar el uso no prescrito que en este estudio alcanzó la cifra del 71%. Conclusión: Las indicaciones de mayor prescripción con IGIV fue purpura trombocitopenia idiopática (PTI) y síndrome de Guillain-Barré (SGB). El uso no prescrito de IGIV en este estudio alcanzó la cifra del 71%.

RESUMO Introdução: A imunoglobulina humana intravenosa inespecífica (IGIV) é um recurso terapêutico valioso em patologias específicas, porém existem condições patológicas para as quais ainda não há estratégia terapêutica definida e devido à semelhança ou plausibilidade biológica alguns prescritores acabam por indica-la. Objetivo: Identificar as indicações para as quais a imunoglobulina humana intravenosa inespecífica (IGIV) foi prescrita no HUS. Metodologia: Foi realizado um estudo observacional transversal descritivo com coleta retrospectiva de informações entre 1° de janeiro de 2017 e 31 de dezembro de 2019. Materiais e métodos: foram revisados 180 prontuários de pacientes que receberam prescrição de pelo menos uma dose de imunoglobulina, foi realizada uma caracterização demográfica, clínica e farmacológica da população em estudo. Além disso, as indicações descritas no prontuário foram comparadas com as indicações aprovadas pelo Invima. Resultados: Mulheres adultas jovens foram identificadas como a população que recebeu IGIV com maior frequência. Da mesma forma, as indicações para as quais a IGIV foi mais frequentemente prescrita foram trombocitopenia roxa idiopática (PTI), síndrome de Guillain-Barré (SGB), lúpus eritematoso sistémico (LES) e icterícia neonatal devido a outras hemólises existentes. As indicações aprovadas pela agência reguladora colombiana (Invima) são inespecíficas, portanto o uso de IGIV é prescrito seja por semelhança ou plausibilidade biológica, o que pode explicar o uso off" label, que neste estudo atingiu a cifra de 71%. Conclusão: As indicações para a maior prescrição de IGIV foram a trombocitopenia roxa idiopática (PTI) e a síndrome de Guillain-Barré (SGB). O uso off" label de IGIV neste estudo atingiu a cifra de 71%.

Application of quantitative detection of multiple-source cytomegalovirus DNA in diagnosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation / 器官移植

Objective To evaluate the diagnostic value of quantitative detection of cytomegalovirus (CMV) DNA from different sources [plasma, sputum and bronchoalveolar lavage fluid(BALF)] for CMV pneumonia after allogeneic hematopoietic stem cell transplantation. Methods Clinical data of 405 recipients undergoing allogeneic hematopoietic stem cell transplantation were retrospectively analyzed. Among them, 19 recipients diagnosed with CMV pneumonia were assigned into the CMV pneumonia group, and 229 recipients with CMV viremia alone, 11 recipients without CMV pneumonia who received fiberoptic bronchoscopy and 16 recipients diagnosed with bacterial or fungal pneumonia based on pathogenic evidence receiving sputum culture were assigned into the control A, B and C groups, respectively. The incidence of CMV pneumonia was summarized. The CMV DNA load of specimens from different sources (plasma, sputum and BALF) of recipients with CMV pneumonia was analyzed. The clinical prognosis of recipients with CMV pneumonia was evaluated. Results Among 405 recipients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases developed CMV pneumonia, and the overall incidence of CMV pneumonia was 4.7%(19/405). The CMV DNA load in the plasma, sputum and BALF of recipients with CMV pneumonia was higher than those in the control A, B and C groups (all P < 0.05). In the 19 recipients, 12 cases were cured after antiviral treatment and 7 died from treatment failure(3 cases abandoned treatment). The fatality was 37%(7/19). Conclusions Quantitative detection of CMV DNA in the plasma, sputum and BALF may increase the diagnostic rate of CMV pneumonia, thereby improving clinical prognosis of recipients undergoing allogeneic hematopoietic stem cell transplantation.

IgA removal by plasma component Ⅱ solution: A comparative study of different filter membrane combinations / 中国输血杂志

【Objective】 To compare the effect of different combinations of filter membranes on the removal of IgA by component Ⅱ solution. 【Methods】 The dissolved solution of component Ⅱ was filtered with different combinations of filter membranes, and the turbidity, IgA residue, molecular size distribution and purity were compared. 【Results】 After filtering through the combination of NA-16+ Millpore 0.5μ, NA-16+ EmphazeTMAEX HP, and ZetaPlus™ + Emphaze™AEX HP filter membranes, the turbidity of the filtrate decreased by 35.5%(22.4/63.1), 39.2%(24.8/63.3) and 59.8%(37.4/62.5), the IgA residue decreased by 5.8%(14.77/253.70), 20.0%(50.90/254.00) and 44.3%(112.13/253.33), respectively.Molecular size distribution was 99.60%, 99.85% and 100%, and the purity was 100%, 100% and 100%, respectively. 【Conclusion】 The combination of ZetaPlus™ + Emphaze™AEX HP filter membrane can not only effectively remove IgA in the dissolution solution of component Ⅱ with other quality indicators remaining high-level, which can be used in IVIG large-scale production process.

Micro-determination on activating complement in detecting biological properties of Fc fragment of IVIG / 中国输血杂志

【Objective】 To improve method for determinating of biological potency of IgG Fc fragment in Chinese Pharmacopoeia and establish a method which is suitable for enzyme-labeled instrument. 【Methods】 The biological properties of FC fragment of IVIG in Chinese Pharmacopiea(General 3514) was adjusted, including sensitization process, sample treatment and dynamic curve parameters. Meanwhile, the kinetic curve of hemolysis was fitted with Origin, which made the method more suitable for enzyme plate. The biological properties of Fc fragment of IVIG was calculated by kinetics curve reaction of reference and sample. 【Results】 The method are stable, the RSD of repeatability and intermediate is 10%, also with significant improvement in efficiency. 【Conclusion】 The detection of properties of Fc fragment of IVIG is stable and efficient, it can be used for properties of Fc fragment of IVIG.

Anti NMDA receptor encephalitis: a potentially treatable encephalitis

Anti NMDA receptor encephalitis is autoimmune encephalitis where antibodies are directed against NMDA receptor subunit. It represents a new category of immune-mediated disorder that is often paraneoplastic, presenting with neuropsychiatric symptoms, which is treatable and can be diagnosed serologically affecting both children and adults. Patient can have variable clinical presentation ranging from prodromal illness, neuropsychiatric symptoms, seizures, autonomic instability, hyperkinesias, catatonia, hypoventilation and with or without an associated teratoma. A positive serum or CSF sample screening for antibodies to the NMDA receptor subunit is confirmative. Supportive findings include CSF study, EEG and MRI Brain. The first-line therapies includes IVIG, corticosteroids or plasma exchange. Second line immunotherapy is rituximab or cyclophosphamide or both. Given the high mortality rate (up to 25%), the likelihood of presentation across the age range and the potential for treatment, a high index of suspicion is warranted by clinicians. Authors report a case of a 5 year old child with anti NMDA receptor encephalitis who responded well to IVIG therapy.

A case of primary immunodeficiency: hyper IgM syndrome

Hyper IgM syndrome are group to disorders characterized by elevated serum level of IgM and low or absent serum levels of IgG, IgA and IgE the mechanism of HIGM is immunoglobulin Class-Switch Recombination (CSR) failure and Somatic Hyper Mutation (SHM). This diagnosis should be considered in any patient presenting with hypogammaglobulinemia, with low or absent IgG and IgA and normal or elevated IgM level. In the present case report, this was a 6-year-old male child who had history of recurrent respiratory tract infections who presented with otitis media and persistent fever spikes. Immunoglobulin studies revealed a pattern consistent with hyper IgM.

Clinical Profile, Electrodiagnostic Variations, Treatment and Outcome in Guillain-Barré Syndrome: Prospective Study of 78 Patients

Introduction: Guillain–Barre syndrome (GBS) is an acutepolyradiculoneuropathy with varied severity of presentation.Objectives: To study clinical presentation, electrodiagnosticvariations, hospital care and outcome of patients of GuillainBarre Syndrome (GBS). Current research aimed to studyefficacy of Plasmapharesis and Intravenous Immunoglobulin(IVIG) in patients of GBS.Material and Methods: 78 patients of GBS were studiedin detail including history, clinical examination andinvestigations. Patients were treated with Plasmapharesis andIVIG; and outcome was observed.Results: Commonest age group affected was 13-40 yrs.The male:female ratio was 1.2:1. Antecedent infection werepresent in 42 out of 78 patients. Quadriparesis was presentin 74 patients and paraparesis in four patients. Cranial nerveinvolvement was seen in 47 out of 78 patients. Areflexia wasfound in all 78 patients. Albuminocytologic dissociation waspresent in 44 out of 61 patients underwent CSF examination.NCV findings show conduction velocity slowing, delayedf latencies in 92% patients. Out of 72 patients, 33[43%]required mechanical ventilation. Out of 78 patients, 71 weretreated with Plasmapharesis and seven patients were treatedwith IVIG. Out of 78 patients 56 [72%] patients recoveredcompletely, 19 [24%] patients died and three [four%] patientsdeveloped severe neurologic deficit.Conclusion: GBS is more common in male as compare tofemale. Commonest presentation is paresthesia in legs andascending paralysis. Patients who received treatment early inthe course of disease had faster recovery. Plasmapheresis andIVIG both showed similar efficacy in treating GBS.

Maternal and perinatal outcome of Evan’s syndrome: a 5 years study in a tertiary care centre

Background: Evans syndrome is a rare autoimmune disorder characterized by simultaneous or sequential presence of a positive antiglobulin test, autoimmune haemolytic anemia (AIHA), and immune thrombocytopenia (ITP). It is characterised by frequent exacerbations and remissions within a chronic course. It was first described by Robert Evans in 1951.  Incidence of AIHA is 1 per 75 - 80,000 and ITP is 5.5 /100000 per general adult population.  Incidence of Evans syndrome is 1.8% to 10% of patients with ITP. Objective was to study the maternal and perinatal outcome of women with Evans syndrome (E).Methods: About 4 antenatal mothers were identified with Evans syndrome at St. Johns medical college and hospital, Bengaluru during the study period of 5 years from July 2013-July 2017. They were followed up during their antenatal, intra natal and postnatal period and outcomes were studied. All patients included in the study fulfilled the criteria for Evans syndrome.Results: There were 4 cases of Evans syndrome, with a total number of deliveries of 11859, during this 5 year study. Incidence was 0.09 per 1000 births. All patients presented with bleeding manifestations ranging from mucosal haemorrhage to subarachnoid haemorrhage (SAH) at the time of diagnosis. All patients were on treatment with either 1st or 2nd line of management with corticosteroids/ azathioprine. None had bleeding during pregnancy after the initiation of treatment. Patients had antenatal complications like preeclampsia 25%, IUGR 25%, oligohydraminos 50%, IUD 25%. 2 patients received platelet transfusions intrapartum. None had intrapartum or postpartum haemorrhage. There were no maternal and neonatal mortality.Conclusions: Evans syndrome in pregnancy is a rare condition and requires multi disciplinary approach involving specialists from obstetrics, neonatology, and hematology. Close maternal and fetal surveillance and management during pregnancy is essential to increase the possibility of a favourable pregnancy outcome in these women.

Intravenous Immunoglobulin Controls Th17 Cell-Mediated Osteoclastogenesis

The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine–induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14⁺ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14⁺ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4⁺ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell–mediated osteoclastogenesis.

Establishment of a new scoring model for IVIG non-response of Kawasaki disease / 国际儿科学杂志

Objective To analyze the possible risk factors of IVIG non-response of Kawasaki disease (KD),Shanghai Children's Hospital and Shanghai Junze Software develop an research platform,which is based on E-Science model.Through the mathematical model by integrating the risk factors to explore the method of effective prediction for IVIG non-response,and to provide the clinical basis for timely and effective treatment and prognosis of the disease.Methods The data of KD children who were hospitalized in Shanghai Children's Hospital from January 2013 to November 2016 were included.The indexes included gender,age,time of IVIG treatment,and laboratory examinations.The multivariate logistic regression was used to analyze the influencing factors of IVIG non-response.The indexes in the model were deduced according to the independent variables of the logistic regression equation.The ROC curve and the area under the curve were calculated for the new prediction model.The sensitivity and specificity of the new prediction model were calculated according to the cutoff value.Finally,the new model was compared with the Kobayashi and Egami scoring model.Results The levels of CRP,NLR,LDH,ALB and FDP in children with KD were influencing factors for IVIG nonresponse (P ＜ 0.05).According to the logistic regression equation,the sensitivity and specificity of the model used to predict IVIG non-response were 69.7％ and 80.4％,respectively,and the area under the ROC curve was 0.825 (95％ CI:0.769-0.882).Kobayashi and Egami scoring models were tested,the sensitivity and specificity of the new scoring system were better than previous ones.Condusion The scoring model established in this study has a good effect in predicting IVIG non-response in KD patients and could be used in clinical practice,and it is worthy to be validated and adjusted by large-scale data.