Correlation of IL-1, IL-6, IL-10 Concentrations to Ovarian Hyperstimulation Syndrome and Effect of Intravenous Immunoglobulin on Ovarian Hyperstimulated Rats

Objective To investigate the correlation of interleukin（IL）-1,IL-6 and IL-10 concentrations to ovarian hyperstimulation syndrome（OHSS） and whether intravenous immunoglobulin（IVIG） has the effects on ovarian hyperstimulated rats. Methods Immature female Wistar rats were divided into control group, OHSS group （n=13） and IVIG group（n=13）. For the latter two groups, pregnancy mare serum gonadotropin（PMSG）and human chorionic gonadotropin（hCG） were given to induce OHSS, and rats in IVIG group were treated with immunoglobulin. Forty-eight hours after administration of hCG, capillary permeability was evaluated from the Evans blue dye（EB） concentration in the ovaries and the EB concentration in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. Rats＇ blood samples and ovaries were obtained to be measured for IL-1, IL-6 and IL-10 by ELISA. Results In OHSS group, total weights of bilateral ovaries and the ovarian EB concentration were significantly higher than those in others（P〈0.05）. Both serum and ovarian concentrations of IL-1 were significantly higher in OHSS and IVIG groups than those in control group （P〈0.05）. The ovarian concentrations of IL-6 and IL-10 in IVIG group were significantly lower than those in control group（P〈0.05）. Furthermore, the ovarian IL-10 concentration in IVIG group was significantly lower than that in OHSS group（P〈0. 05）. Conclusion Inflammation involved IL-1 in OHSS rats plays an important role. Vascular permeability was mostly increased in ovaries of hyperstimulated rats. It appears that ovaries of OHSS rats may be the primary places of inflammation. IVIG treatment resulted in statistically significant reductions in ovaries＇ weights and ovarian vascular permeability of OHSS rats, with a decreased level of ovarian IL-10. It implys that IVIG have a beneficial effect in reducing the severity of OHSS in the experimental model maybe by restrainning IL-10.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

BACKGROUND： The established procedure for ABO-incompatible liver transplantation（ABO-I LT） was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin（IVIG） for ABO-I LT in patients with acute liver failure（ALF）.METHODS： The data from 101 patients who had undergone liver transplantation（LT） for ALF were retrospectively analyzed.The patients were divided into two groups： ABO-compatible liver transplantation group（ABO-C LT, n=66） and ABO-I LT group（n=35）. All the patients in the ABO-I LT group received a single dose of rituximab（375 mg/m2） and IVIG（0.4 g/kg per day） at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol.Quadruple immunosuppressive therapy including basiliximab,corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.RESULTS： The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%,respectively（P〉0.05）, and the graft survival rates were 80.0%and 86.3%, respectively（P〉0.05）. Two patients（5.7%） suffered from antibody-mediated rejection in the ABO-I LT group.Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.CONCLUSIONS： The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Role of intravenous immunoglobulin in suspected or proven neonatal sepsis

Neonatal sepsis remains the major cause of mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay in newborn infants. Despite of advances in technology and optimal antibiotic treatment,incidence of neonatal sepsis and its complications remains unacceptably high especially in developing countries. Premature neonates in particular are at higher risk due to developmentally immature host defence mechanisms. Though not approved by Food and Drug Administration(FDA) U. S. A,off label use of intravenous immunoglobulin as prophylactic or adjuvant agent in suspected or proven neonatal infections continues in many countries. In a recent large multicenter clinical trial by International Neonatal Immunotherapy Study(INIS) group, the use of polyvalent IgG immune globulin was not associated with significant differences in the risk of major complications or other adverse outcomes in neonates with suspected or proven sepsis. Hence,use of intravenous immunoglobulin in suspected or proven neonatal sepsis is not recommended. The expense of prophylactic use of intravenous immunoglobulin administration for both term and preterm newborn population,given the minimal benefit as demonstrated by many individual studies and by meta-analysis is not justified.

Intravenous Immunoglobulin Treatment of Recurrent Miscarriage:an Update of Placebo-controlled Trials

Background Immunological disturbances which may be treated with intravenous immunoglobulin (IvIg) play a significant role in the majority of patients with recurrent miscarriage (RM). The present study aimed to review the current knowledge about IvIg treatment in RM primarily based on results from published placebo controlled trials. Seven placebo controlled trials were identified comprising a total of 343 patients. The background variables, the treatment protocols and the results were extremely different between the trials. Among the patients with secondary RM, a meta analysis showed that the pooled odds ratio for live birth among IvIg treated women compared with women infused with placebo was 1.69 (95 % CI = 0.72～3.96, not significant). IvIg also seemed to be efficacious in patients with repeated second trimester intrauterine fetal deaths. A new big placebo controlled trial should be conducted which focus on RM patients with secondary RM or recurrent second trimester fetal deaths. Sufficient IvIg doses should be given with optimal time intervals.

Haemolytic Anaemia Following High Dose Intravenous Immunoglobulin Treatment for Epidermolysis Bullosa Acquisita

Background: Epidermolysis bullosa aquisita (EBA) is a severe acquired blistering skin disease that is often resistant to prednisolone but can respond well to intravenous immunoglobulin infusion (IVIg). Main Observations: We describe the case of a 35 years old male patient with EBA who developed clinically significant haemolytic anaemia with a drop in Hb from 15.3 g/dL to a nadir of 8.4 g/dL within 5 days post IVIg infusion. The patient was blood group A and the IVIg batch was found to have a high titre of anti-A immunoglobulin. Conclusions: IVIg is an effective treatment for EBA. Haemolysis associated with IVIg has not previously been reported in the dermatology literature but review of data from other specialties shows that the problem is well recognised. Dermatologists using IVIg should be aware of this potential complication and patients should be consented appropriately and warned about this potential side effect.

A Systematic Review Incorporating Meta-Analysis on the Effectiveness of Intravenous Immunoglobulin Versus Corticosteroids in the Treatment of Pediatric Myocarditis

Background:Concerns have been raised about the efficacy of intravenous immunoglobulin and corticosteroids in pediatric myocarditis;however,the relationship between the risk and efficacy of these two therapies in children with myocarditis varies.Methods:A systematic review on seventeen studies was conducted in July 2020,which included 1,960 subjects at the baseline,with 788 receiving intravenous immunoglobulin and 142 receiving corticosteroids.The mean difference(MD)or odds ratio(OR)with 95%confidence intervals(Cis)was calculated to assess the prognostic role of both treatments using dichotomous and continuous methods with random or fixed-effect models.Results:The use of intravenous immunoglobulin was significantly associated with a lower mortality rate or heart transplantation in children with myocarditis(OR,0.55;95%CI,0.40-0.77,^<0.001)compared with the control group.However,corticosteroids were not significantly associated with the same parameters(OR,0.72;95% CI,0.31-1.63,p=0.43).The use of intravenous immunoglobulin was not significantly related to improving left ventricular ejection in children with myocarditis(OR,2.30;95% CI,-9.65-14.25,p=0.71)and so were corticosteroids(MD,5.17;95% CI,-0.26-10.60,p=0.06).Conclusion:The use of intravenous immunoglobulin might have an independent risk relationship with a lower mortality rate or heart transplantation and is recommended in children with myocarditis to prevent complications.

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in children

Background We aimed to explore predictive measures for intravenous immunoglobulin(IVIG)resistance in children with Kawasaki disease(KD).Methods Patients diagnosed with KD were enrolled in this study.Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups.Independent predictors of IVIG resistance were analyzed,and a predictive model for KD children with IVIG resistance was constructed.Results A total of 277 children with KD,180 boys and 97 girls,aged 2-128(median 23)months,were enrolled in the study.Compared with the IVIG-responsive group,the IVIG-resistant group had higher levels of the peripheral neutrophil count,mean platelet volume,mean platelet volume-to-lymphocyte ratio and C-reactive protein,and total serum bilirubin,but lower levels of peripheral lymphocyte count,serum albumin and serum prealbumin.Age(in months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis.A logistic regression model and a scoring system were set up,where cut-off values of—0.46 and 6.5 points yielded sensitivities of 83.9%and 77.4%,and specificities of 74.8%and 61.0%,respectively.The areas under the curve(AUC)were 0.808 in the logistic regression model,and 0.750 in the scoring system.Conclusion Our model for predicting IVIG-resistant children with KD,involving age(months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment,is helpful for clinical prediction of children with IVIG-resistant KD.

Adverse events of intravenous immunoglobulin infusions:a three-year retrospective study in China

Intravenous immunoglobulin(IVIG) is biological product, which is extensively used in pediatric patients, with high adverse effects on children among different brand preparations. In the present study, we aimed to describe the adverse events of pediatric patients given IVIG infusions in China. Data were collected from all patients receiving IVIG infusion at the largest children’s hospital in Ningbo of China form January 2015 to December 2017. Descriptive statistics was used. A total of 2100 patients received IVIG infusion. All the patients who experienced adverse reactions were children(0.48%), with the highest frequency of infusion among those age 1 to 3 years old(40%). Among 10 infusions with adverse reactions, the most common indication was Kawasaki disease(40%) followed by severe pneumonia(30%). Rash was the most common adverse event(80%), followed by chest pain & cough(50%) and cyanosis(40%). Adverse events were observed to occur most frequently within 30 min from onset of infusion. Most of the reactions occurred with the large dose and the indications of used for. Since the hospital changed the brand, the incidence of adverse reactions was decreased from 1.39% to 0.13%. In this study, 0.48% of pediatric patients given IVIG infusions experienced adverse events. Anaphylactoid reaction was the most common manifestation. Symptoms occurred within 30 min from onset of infusion, which were affected by the dose, the value of lgE, the indications and the different brands.

Transient positive antimitochondrial M2 in sera of patients with connective tissue diseases after intravenous immunoglobulin infusions

Background:Although antinuclear antibodies(ANAs),anti‐SSA and anti‐Ro52,are present in immunoglobulin preparations,it is unknown whether intravenous immunoglobulin(IVIG)therapy influences the testing of serum autoantibodies in patients with connective tissue diseases(CTDs).The present study aimed to investigate the dynamic change over time of serum ANA‐related autoantibodies in patients with CTDs receiving IVIG therapy.Methods:Serum ANA‐related autoantibodies were monitored in two patients with CTD before IVIG therapy and at different times after therapy.These autoantibodies were tested in different batches of immunoglobulin preparations from seven pharmaceutical companies.Results:One patient developed a new ANA pattern(cytoplasmic dense fine speckled pattern,AC‐19)just after IVIG therapy.Both patients developed de novo positivity for AMA‐M2 and anti‐SSA,but returned negative 1 month after IVIG therapy.The residual liquid in patients'immunoglobulin preparations showed positive ANAs with a high titer of AC‐19(1:640),a low titer of the nuclear fine speckled pattern(AC‐4,1:80),positive AMA‐M2,and positive anti‐SSA.ANA‐related autoantibodies were tested in 16 batches of immunoglobulin preparations and all had positive ANAs with two patterns:AC‐19(1:640 or 1:320)and AC‐4(1:80).AMA‐M2 and anti‐SSA were positive in 100%of the batches.Conclusion:Our study highlights high‐titer AMA‐M2 autoantibodies in immunoglobulin preparations and suggests their transient transfer into a patient's circulation via IVIG therapy.To avoid incorrect clinical decisions based on postinfusion antibody titers,our data recommend retesting 1–2 months after high‐dose IVIG immunomodulatory treatment.

PLACENTAL INTRAVENOUS IMMUNOGLOBULIN (PtIVIG) FOR TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE (CGVHD)

Plasma immunoglobulin has been used widely in clinic for the prophylaxis and treatment of infections in patients after bone marrow transplantation(BMT).However,there are no hard data demonstrating that it can act against GVHD,

A case of pyoderma gangrenosum responding to high-dose intravenous immunoglobulin therapy

Pyoderma gangrenosum （PG） is a rare ulcerative cutaneous condition with distinctivecharacteristics, and the aetiology is not clear yet. PG is commonly associated with inflammatory bowel disease including ulcerative colitis and Crohn＇s disease. This condition is within the spectrum of the neutrophilic dermatoses. The features of PG are not specific histopathologically. Commonly, it is characterized by the presence of marked neutrophilic infiltrates in the dermis. The treatment of PG usually requires systemic corticosteroids or other immunospressive medications, and its course is chronic and relapsing. Some cases are resistant to these treatments. On the other hand, long-term usage of those medications naturally causes serious side effects, and an alternative effective and safe therapy is required to avoid the clinical problems associated with the drugs.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Evaluation of the Immunoglobulin Use in Inflammatory Systemic and Immuno-Mediated Illnesses in a Tertiary Hospital

The object of this study is to assess the Ivlg （intravenous immunoglobulin） use in inflammatory systemic and immune-mediated illnesses, in patients older than 18 years in a tertiary hospital. The assessment also intends to ensure if the clinical indications matched with the evidence-based clinical guidelines recommendations of use. Analytical, observational, transversal and retrospective study carried out during 2012. Patients with inflammatory systemic and immuno-mediated illnesses, older than 18 years old, were included. The data collected were： age, sex, number of administrations, dosage, frequency, commercial brand and the indication for what the Ivlg treatment has been prescribed. As a reference guide the British Health Department Clinical Guidelines for Immunoglobulin Use （2nd edition, 2008, and 2nd edition update 2011） and its Spanish adaption were used. The lvlg treatment was justified by a grade of recommendation A, B or C in 41% of the indications. Thus in 59% （grey indications or unclear diagnosis） the IvIg use would be questionable because of its weak evidence. It was found one indication for what the prescription of IvIg was clearly not recommended. The inflammatory systemic and immune-mediated diseases include many pathologies for what the IvIg use has not been properly studied. There is a need of consensus guidelines for IvIg use to guide doctors and pharmacists in their clinical practice. Moreover, it is important to prioritize which indications and circumstances are of first importance to have their supply guaranteed.

Pure red cell aplasia due to parvovirus B19 infection after liver transplantation:A case report and review of the literature

Pure red cell aplasia （PRCA） due to parvovirus B19 （PVB19） infectiori after solid organ transplantation has been rarely reported and most of the cases were renal transplant recipients, Few have been described after liver transplantation. Moreover, little information on the management of this easily recurring disease is available at present. We describe the first case of a Chinese liver transplant recipient with PVB19-induced PRCA during immunosuppressive therapy. The patient suffered from progressive anemia with the lowest hemoglobin level of 21 g/L. Bone marrow biopsy showed selectively inhibited erythropoiesis with giant pronormoblasts. Detection of PVB19-DNA in serum with quantitative polymerase chain reaction （PCR） revealed a high level of viral load. After 2 courses of intravenous immunoglobulin （IVIG） therapy, bone marrow erythropoiesis recovered with his hemoglobin level increased to 123 g/L. He had a lowlevel PVB19 load for a 5-too follow-up period without recurrence of PRCA, and finally the virus was cleared. Our case indicates that clearance of PVB19 by IVIG in transplant recipients might be delayed after recovery of anemia.

Human parvovirus B19-associated early postoperative acquired pure red cell aplasia in simultaneous pancreas-kidney transplantation:A case report

BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early postoperative infection.In this current study,we report the case of a Chinese patient who experienced the disease in the early postoperative period.CASE SUMMARY A 63-year-old man,with type 2 diabetes and end-stage renal disease,received a brain dead donor-derived SPKT.Immunosuppression treatment consisted of tacrolimus,prednisone,enteric-coated mycophenolate sodium(EC-MPS),and thymoglobulin combined with methylprednisolone as induction.The hemoglobin(Hb)level declined due to melena at postoperative day(POD)3,erythropoietinresistant anemia persisted,and reticulocytopenia was diagnosed at POD 20.The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43.Metagenomic next-generation sequencing(mNGS)of a blood sample identified HPV B19 infection at POD 66.EC-MPS was withdrawn;three cycles of intravenous immunoglobulin(IVIG)infusion therapy were administered;and tacrolimus was switched to cyclosporine.The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period.The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements.CONCLUSION HPV B19-associated aPRCA can occur at an early period after SPKT.An effective therapy regimen includes IVIG infusion and adjustment of the immunosuppressive regimen.Moreover,mNGS can be used for the diagnosis and to reflect disease progression.

An effective initial polytherapy for children with West syndrome

Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.

Modern approaches to incompatible kidney transplantation

The presence of human-leukocyte antigen （HLA）-antibodies and blood group incompatibility remain a large barrier to kidney transplantation leading to increased morbidity and mortality on the transplant waiting list. Over the last decade a number of new approaches were developed to overcome these barriers. Intravenous immunoglobulin （IVIG） remains the backbone of HLA desensitization therapy and has been shown in a prospective, randomized, placebo controlled trial to improve transplantation rates. Excellent outcomes with the addition of rituximab （anti-B cell） to IVIG based desensitization have been achieved. There is limited experience with bortezomib （anti-plasma cell） and eculizumab （complement inhibition） for desensitization. However, these agents may be good adjuncts for patients who are broadly sensitized with strong, complement-fxing HLA antibodies. Excellent short and long-term outcomes have been achieved in ABO incompatible transplantation with the combination of antibody removal, B cell depletion, and pre-transplant immunosuppression. Kidney paired donation has emerged as a reasonable alternative for programs who cannot provide desensitization or in conjunction with desensitization. Future therapies directed toward cytokines that alter B cell proliferation are under investigation.

Kawasaki disease without changes in inflammatory biomarkers:A case report

BACKGROUND Kawasaki disease(KD)is diagnosed based on clinical features.Blood tests and other tests are auxiliary diagnostic tools.Since KD is a disease caused by arterial inflammation,many patients with KD have elevated levels of inflammatory biomarkers,such as C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and serum amyloid A protein(SAA)in blood tests.We report our experience of a patient with KD who did not have elevated levels of inflammatory biomarkers.CASE SUMMARY A 1-year-old boy presented with a 3-day history of fever.Five of the six symptoms of KD were observed,except for changes in the lips and oral cavity.Blood tests revealed no elevation in CRP,ESR,or SAA levels.Although the blood test results were atypical,the patient was diagnosed with KD based on clinical symptoms and was admitted to the hospital for treatment.The patient was administered intravenous immunoglobulin(IVIG)and aspirin.Despite commencing treatment,the fever persisted;therefore,additional IVIG was administered,the dosage of aspirin was increased,and ulinastatin was added.Three doses of IVIG were administered and the fever resolved on day 11 of KD symptoms started.Blood tests performed during hospitalization showed normal levels of inflammatory biomarkers.We examined leucine-rich alpha-2-glycoprotein 1-a protein that is elevated during the acute phase of KD.The protein levels did not increase during hospitalization.CONCLUSION This case suggests the need to identify criteria and biomarkers for detecting KD conditions that do not require KD treatment.

Hematologic diseases: High risk of Clostridium difficile associated diarrhea

AIM: To investigate the incidence and clinical outcome of Clostridium difficile (C. difficile) associated diarrhea (CDAD) in patients with hematologic disease.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies:A case report

BACKGROUND Paraneoplastic neurological syndrome(PNS)is a rare complication in patients with cancer.PNS can affect the central,peripheral,autonomic nervous system,neuromuscular junction,or muscles and cause various neurological symptoms.Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibodypositive neurological paraneoplasms are common,but coexistence of both types has not been described in the literature.CASE SUMMARY Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers.A 55-year-old woman was admitted to our hospital with unsteadiness while walking.The patient had a history of breast cancer two years previously.Chest computed tomography revealed a 4.6 cm×3.6 cm mass in the right lung,which was diagnosed as small-cell lung cancer(SCLC).Blood test was positive for anti-Yo antibodies,and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies,and the neurological symptoms were considered to be related to the paraneoplasm.The patient was treated with a course of intravenous immunoglobulin,without noticeable improvement.After being discharged from hospital,the patient underwent regular chemotherapy for SCLC and periodic reviews.The patient’s neurological symptoms continued to deteriorate at the follow-up visit in April 2021.CONCLUSION This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies.The clinical appearance of two or more paraneoplastic tumors requires additional attention.