Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1.

Immunoglobulin G (IgG) antibodies are major drivers of inflammation during infectious and autoimmune diseases. In pooled serum IgG (IVIg), however, antibodies have a potent immunomodulatory and anti-inflammatory activity, but how this is mediated is unclear. We studied IgG-dependent initiation of resolution of inflammation in cytokine- and autoantibody-driven models of rheumatoid arthritis and found IVIg sialylation inhibited joint inflammation, whereas inhibition of osteoclastogenesis was sialic acid independent. Instead, IVIg-dependent inhibition of osteoclastogenesis was abrogated in mice lacking receptors Dectin-1 or FcγRIIb. Atomistic molecular dynamics simulations and super-resolution microscopy revealed that Dectin-1 promoted FcγRIIb membrane conformations that allowed productive IgG binding and enhanced interactions with mouse and human IgG subclasses. IVIg reprogrammed monocytes via FcγRIIb-dependent signaling that required Dectin-1. Our data identify a pathogen-independent function of Dectin-1 as a co-inhibitory checkpoint for IgG-dependent inhibition of mouse and human osteoclastogenesis. These findings may have implications for therapeutic targeting of autoantibody and cytokine-driven inflammation.

Neutralizing Autoantibodies against Interleukin-10 in Inflammatory Bowel Disease.

We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion. We conclude that neutralizing anti-interleukin-10 autoantibodies may be a causative or modifying factor in IBD, with potential implications for therapy. (Funded by the National Institute for Health and Care Research and others.).

Trial of Intravenous Immune Globulin in Dermatomyositis.

BACKGROUND: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated. METHODS: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.0 g per kilogram of body weight or placebo every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIG could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of six measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement. Key secondary end points included at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60), and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index. RESULTS: A total of 95 patients underwent randomization: 47 patients were assigned to the IVIG group, and 48 to the placebo group. At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P<0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events. CONCLUSIONS: In this 16-week trial involving adults with dermatomyositis, the percentage of patients with a response of at least minimal improvement based on a composite score of disease activity was significantly greater among those who received IVIG than among those who received placebo. IVIG was associated with adverse events, including thromboembolism. (Funded by Octapharma Pharmazeutika; ProDERM ClinicalTrials.gov number, NCT02728752.).

Different dose aspirin plus immunoglobulin (DAPI) for prevention of coronary artery abnormalities in Kawasaki disease: Study protocol for a multi-center, prospective, randomized, open-label, blinded end-point, non-inferiority trial.

BACKGROUND: Kawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease. METHODS: This is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg-1·d-1) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg-1·d-1) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography. CONCLUSIONS: There is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR2300072686.

Hepatitis B screening in hematology patients receiving intravenous immunoglobulin.

BACKGROUND: Transient positivity for hepatitis B core antibody (Anti-HBc) following intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin exposure is a well-described phenomenon. The aim of this study was to retrospectively review Hepatitis B viral screening practices in IVIG recipients in a hematology specific cohort at a single center. METHODS: Electronic databases were analyzed to identify all hematology patients who received IVIG from September 2022 to March 2022 at a single Irish center (n = 43). The proportion of patients that had a baseline anti-HBc tested prior to IVIG receipt was assessed as well as the proportion of patients that developed a transiently positive anti-HBc following IVIG exposure. Data were also collected relating to signal cut-off ratios in patients with detectable anti-HBc post-IVIG. RESULTS: 58.1% of patients had at least one serological hepatitis B viral test sent prior to IVIG exposure. Anti-HBc was the least common serological investigation performed prior to IVIG exposure (21% of recipients). A positive or equivocal "low level antibody" was identified in 15% of recipients and this was proven to be transient in all cases. CONCLUSION: The minority of hematology patients had a baseline anti-HBc assessed prior to IVIG exposure. All patients in this study had the potential to require further immunosuppressive therapies, which could be limited by a misleading anti-HBc result. We therefore advocate for baseline anti-HBc testing to be performed prior to IVIG exposure in hematology patients and for cautious interpretation of anti-HBc results taking into account signal cut-off ratios post-IVIG exposure.

Intravenous immunoglobulin for the treatment of severe maternal alloimmunization: individual patient data meta-analysis.

OBJECTIVE: This study aimed to investigate the outcomes associated with the administration of maternal intravenous immunoglobulin in high-risk red blood cell-alloimmunized pregnancies. DATA SOURCES: Medline, Embase, and Cochrane Library were systematically searched until June 2023. STUDY ELIGIBILITY CRITERIA: This review included studies reporting on pregnancies with severe red blood cell alloimmunization, defined as either a previous fetal or neonatal death or the need for intrauterine transfusion before 24 weeks of gestation in the previous pregnancy as a result of hemolytic disease of the fetus and newborn. METHODS: Cases were pregnancies that received intravenous immunoglobulin, whereas controls did not. Individual patient data meta-analysis was performed using the Bayesian framework. RESULTS: Individual patient data analysis included 8 studies consisting of 97 cases and 97 controls. Intravenous immunoglobulin was associated with prolonged delta gestational age at the first intrauterine transfusion (gestational age of current pregnancy - gestational age at previous pregnancy) (mean difference, 3.19 weeks; 95% credible interval, 1.28-5.05), prolonged gestational age at the first intrauterine transfusion (mean difference, 1.32 weeks; 95% credible interval, 0.08-2.50), reduced risk of fetal hydrops at the time of first intrauterine transfusion (incidence rate ratio, 0.19; 95% credible interval, 0.07-0.45), reduced risk of fetal demise (incidence rate ratio, 0.23; 95% credible interval, 0.10-0.47), higher chances of live birth at ≥28 weeks (incidence rate ratio, 1.88; 95% credible interval, 1.31-2.69;), higher chances of live birth at ≥32 weeks (incidence rate ratio, 1.93; 95% credible interval, 1.32-2.83), and higher chances of survival at birth (incidence rate ratio, 1.82; 95% credible interval, 1.30-2.61). There was no substantial difference in the number of intrauterine transfusions, hemoglobin level at birth, bilirubin level at birth, or survival at hospital discharge for live births. CONCLUSION: Intravenous immunoglobulin treatment in pregnancies at risk of severe early hemolytic disease of the fetus and newborn seems to have a clinically relevant beneficial effect on the course and severity of the disease.

Prevention of axonal loss after immediate dosage titration of immunoglobulin in multifocal motor neuropathy.

BACKGROUND: To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3-37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow-up. RESULTS: At follow-up, the Z-score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment-free period of 0.3 years (0.2-0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z-scores (0.9-17.0, p = 0.06) was observed in five patients with a treatment-free period of 4.0 years (0.9-9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow-up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss. CONCLUSION: Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.

Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Transfusion-related acute lung injury (TRALI) following intravenous immunoglobulin infusion in a rituximab immunosuppressed patient with long-shedding SARS-CoV-2.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported. CASE PRESENTATION: A 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI. CONCLUSION: IVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected.

Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS. METHODS: This phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow-up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated. RESULTS: The analysis included 57 participants (eculizumab, n = 37; placebo, n = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45-1.97; p = .89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow-up period. No new safety signals for eculizumab were identified. INTERPRETATION: Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS.

Diagnosis and management of cancer therapy-related myocarditis in a young female: A case report and review of literature.

BACKGROUND: The treatment of choice for Extra-osseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET), a rare neoplasm, is the VAC/IE regimen. This regimen includes Doxorubicin, Vincristine, Cyclophosphamide, Ifosfamide, and Etoposide, all of which have cardiotoxic effects. Myocarditis, a potentially threatening side effect following cancer therapy, can be accurately managed and diagnosed. CASE PRESENTATION: In the current study, we report the case of a 19-year-old female with a mass on the abdominal wall, diagnosed with ES/PNET. She was treated with the VAC/IE regimen. A month after the last session of chemotherapy, she experienced dyspnea. Upon evaluation, a high level of troponin and a low left ventricular ejection fraction (LVEF) were detected via transthoracic echocardiography. She was treated with anti-heart failure drugs, but the response was unsatisfactory. The possibility of Cancer therapy-related myocarditis was suspected, and cardiac magnetic resonance imaging (CMR) confirmed acute myocarditis. This patient exhibited a significant response to intravenous immunoglobulin (IVIG), with her LVEF improving from 30-35% to 50% within three months. CONCLUSION: In this case, based on negative tests and the absence of viral signs and symptoms, Cancer therapy-related myocarditis is highly suspected as the cause of myocarditis. This case underscores the importance of accurately utilizing CMR as a non-invasive method for diagnosing myocarditis. It effectively highlights the identification of reversible myocarditis with appropriate treatment and the notable response to IVIG, suggesting its potential as a favorable treatment for myocarditis in younger patients.

Veno-Occlusive Disease: A Life-saving Novel Approach With Plasma Exchange, IVIG, and Steroid, Without Defibrotide.

INTRODUCTION: Hepatic veno-occlusive disease (VOD) is a critical medical emergency with a high mortality rate of up to 90% if not promptly treated. Defibrotide is the only approved medication for VOD treatment, exhibiting anti-inflammatory, antithrombotic, and anti-ischemic properties. This report presents a case of severe VOD in a patient undergoing acute lymphoblastic leukemia (ALL) treatment. CASE PRESENTATION: We describe the successful and rapid treatment of severe VOD in an ALL patient using therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and methylprednisolone (MPZ). The patient showed significant clinical and laboratory improvement after this combined therapeutic approach. CONCLUSION: This case highlights the effectiveness of TPE, IVIG, and MPZ in the treatment of severe VOD in ALL patients, providing insights into alternative therapeutic strategies in the absence of Defibrotide.

Methylprednisolone pulse and prednisolone for intensification of primary treatment in Kawasaki disease patients at high risk of treatment resistance: a multicenter prospective cohort study.

The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospective, observational study was conducted at 28 hospitals in Japan from October 2016 to June 2020. For patients predicted to be resistant to treatment based on a Kobayashi score ≥ 5 and total bilirubin ≥ 1.0 mg/dL, each hospital independently decided to add IVMP followed by prednisolone, prednisolone alone, or nothing to the primary IVIG therapy. In total, 2856 consecutive KD patients were enrolled; of these, 399 (14.0%) were predicted to be treatment resistant. Patients who were resistant to the primary treatment and required additional treatment comprised 59%, 20%, and 26% of the IVIG-alone group, IVIG-plus-prednisolone group, and IVIG-plus-IVMP group, respectively (P < .0001). The CAA incidence (Z score ≥ 2.5) at month 1 was similar among the treatment groups (6.7%, 4.8%, and 7.3%, respectively; P = .66). CAA occurred more frequently in patients who needed third- or later-line therapy.Conclusions: Primary adjunctive corticosteroid therapy improved the treatment response and suppressed inflammation. However, the study found no benefit of adding IVMP to prednisolone therapy. Patients receiving IVIG alone achieved coronary outcomes comparable to those of patients receiving primary adjunctive corticosteroid therapy although they were more likely to require additional rescue treatment. KD inflammation should be resolved no later than the third line of additional treatment to reduce the risk of CAA.Trial registration: University Hospital Medical Information Network Clinical Trials Registry in Japan ( https://www.umin.ac.jp/ctr/index.htm ) under code UMIN000024937.

Impact of pre-delivery medication treatment on delivery outcome in patients with primary immune thrombocytopenia: a cohort study.

BACKGROUND: Clinical research data showed a series of adverse events in the delivery period of primary immune thrombocytopenia (ITP) patients, including high cesarean section rate. Consensus report proposed that for patients with platelet count below 50 × 109/L, prednisone or intravenous immunoglobulins (IVIg) can be given to raise the platelet count in third trimester in preparation for labor. OBJECTIVES: To evaluate the effect of low-dose prednisone or IVIg therapy on delivery outcomes in patients with ITP. STUDY DESIGN: This was a cohort study that included pregnant women with ITP from January 2017 to December 2022. Patients with platelet counts of (20-50) ×109/L at the time of delivery (≥34 weeks) and who had not received any medication before were enrolled in the study. Patients were divided into the pre-delivery medication group (oral prednisone or IVIg) and untreated group according to their preferences. The differences in vaginal delivery rate, postpartum bleeding rate, and platelet transfusion volume between the two groups were compared using t-test, Wilcoxon rank-sum test, and χ2 test. Logistic regression analysis was used to identify the factors affecting vaginal delivery rate and postpartum bleeding rate, and multiple linear regression analysis was used to identify the factors affecting platelet transfusion volume. RESULTS: During the study period, a total of 96 patients with ITP were enrolled, including 70 in the pre-delivery medication group and 26 in the untreated group. The platelet count of pre-delivery medication group was 54.8 ± 34.5 × 109/L, which was significantly higher than that of untreated group 34.4 ± 9.0 × 109/L (p = .004). The vaginal delivery rate of the medication group was higher than the untreated group [60.0% (42/70) vs. 30.8% (8/26), χ2 = 6.49, p = .013]. After adjusting for the proportion of multiparous women and gestational weeks, the results showed that medication therapy during the peripartum period was associated with vaginal delivery (OR = 4.937, 95% CI: 1.511-16.136, p = .008). The postpartum bleeding rates were 22.9% (16/70) and 26.9% (7/26) in the medication group and untreated group, respectively, with no significant difference between the two groups (χ2 = 0.17, p = .789), while the platelet transfusion volume was lower in the medication group than untreated group [(1.1 ± 1.0) vs. (1.6 ± 0.8) U]. CONCLUSION: Pre-delivery medication therapy can increase vaginal delivery rate, reduce platelet transfusion volume, but does not decrease the incidence of postpartum hemorrhage.

What is the context?The high cesarean section rate has always been a prominent pregnancy issue in ITP patients. The data shows that the reason for cesarean section in most ITP patients may be related to early induced labor due to thrombocytopenia or patients' concerns of bleeding events during delivery. The study of treatment during the perinatal period is expected to further increase platelet count and prepare for safer delivery.What is new?To date, no study has focused on pre-delivery treatment for pregnant ITP patients. In this study, patients with a platelet count<50 × 109/L after 34 weeks can experience a significant increase in platelet count after receiving immunoglobulin or prednisone therapy. The results of this study preliminarily demonstrate IVIg or prednisone is a promising pre-delivery treatment for pregnant ITP patients in preparation for labor. The pre-delivery medication therapy can improve the rate of successful vaginal delivery and reduce the consumption of blood products.What is the impact?This study provides further evidence that the target threshold for platelets should be raised in late third trimester, with a platelet count above 50 × 109/L as the standard for delivery, in order to further reduce the cesarean section rate and blood product infusion in ITP patients.

A Case of Intravenous IVIg Interfering with Serological Test Results of HBV.

BACKGROUND: Since Imbach [1] first reported the use of high-dose intravenous immunoglobulin (IVIg) in the treatment of idiopathic thrombocytopenic purpura (ITP) in children, indications for IVIg therapy have been increaseing. At present, IVIg infusion has become an important means of clinical treatment. The phenomenon of anti-HBs and anti-HBc elevation caused by IVIg infusion in patients has been reported in journals, but similar reports in journals related to laboratory diagnosis are rare. METHODS: We reported a case of a patient with immune thrombocytopenia (ITP) which interfered with hepatitis B virus (HBV) serological detection after receiving intravenous IVIg. We used chemiluminescence immunoassay to detect serological markers of HBV. IU/mL was used to represent the detection data of HBsAg and HBsAb and cutoff value was used to represent the detection HBeAg, HBeAb, and HbcAb. RESULTS: The serological markers of HBV were all negative before IVIg infusion. One week after IVIG infusion, the item was tested again, and the results of HBsAb, HBeAb, and HBcAb were positive. As the time increased after infusion, HBsAb, HBeAb, and HBcAb in the patient gradually decreased. CONCLUSIONS: After IVIg infusion, the sudden positive change of HBsAb, HBeAb, and HbcAb in the patient's body was not caused by HBV infection, but caused by the infusion of foreign antibody. This case study shows that physicians should be particularly careful when interpreting results in patients treated with intravenous IVIg involving viral hepatitis B.

Successful treatment with efgartigimod as an add-on therapy in acute attack of anti-AQP4 antibody-positive NMOSD: a case report.

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". CASE DESCRIPTION: We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. CONCLUSION: This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD.

Adequate IVIG dosing is associated with an improved long-term outcome in secondary immunodeficiency: A prospective, non-interventional study.

OBJECTIVE: To assess the safety, tolerability, and effectiveness of the intravenous immunoglobulin (IVIG) Intratect 50 g/L in immunoglobulin replacement therapy (IgRT) in a prospective, large-scale non-interventional study (NIS). The analysis focused upon patients with secondary immunodeficiency (SID), the most frequent indication for IgRT in this NIS. MATERIALS AND METHODS: Patients were enrolled at 123 centers in Germany. Each patient received IVIG as prescribed by the physician, guided by the Summary of Product Characteristics. Data were acquired from medical records and patients' questionnaires. RESULTS: In the NIS, 3,563 patients were documented. The main indication for IgRT was SID (73.2%), followed by primary immunodeficiency (14.7%), immune thrombocytopenia (5.8%), and other indications (6.2%). Among the SID patients, 52.9% were male, mean age was 66.5 years, and most (63.8%) were IVIG-naïve. Their annual infection rate improved from 3.7 before documentation in the NIS to 1.1 during the first year of the study. IgG trough plasma levels increased during treatment (> 6 g/L: 44.5% of SID patients at study entry and 64.8% in long-term treatment) and were associated with a trend toward reduced infection rate (p = 0.08). A 1-year infection analysis showed a significantly lower infection risk in the medium- and high-dose groups than in the low-dose group (p = 0.028 and p = 0.017, respectively). Patients' treatment satisfaction and quality of life improved from baseline. Adverse drug reactions (ADRs) in SID occurred at a low frequency with 0.8% at infusion level. On the patient level, ADRs occurred in 251 (15.3%) SID patients, with chills (7.4%) and pyrexia (0.9%) reported most frequently. CONCLUSION: Effectiveness, safety, and quality of life confirmed the positive benefit-risk profile of IgRT. Higher IVIG dosages per body weight led to higher IgG plasma trough levels, in turn leading to reduced infection rates. Obese patients may need body-weight-adjusted treatment to reduce the risk of infection.

Efficacy and safety of intravenous immunoglobulin therapy in systemic sclerosis: a systematic review.

BACKGROUND AND OBJECTIVE: Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc. METHODS: The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies. RESULTS: From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash. CONCLUSION: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations.

Comparison of efficacy of plasma exchange versus intravenous immunoglobulin as an add-on therapy in acute attacks of neuromyelitis optica spectrum disorder.

INTRODUCTION: Plasma exchange (PE) is considered a Category II option for the treatment of acute attacks and relapse cases of neuromyelitis optica spectrum disorder (NMOSD). However, neurologists are also considering intravenous immunoglobulins (IVIg) as an add-on therapy for this disorder. AIMS: The aim of this study is to evaluate the efficacy of PE in acute attacks of NMOSD when compared with IVIg, in terms of improvement in the Expanded disability status scale (EDSS) and activities of daily living (ADL) scale score and levels of anti-Aquaporin P4 (AQP4) antibody in seropositive patients. METHODS: We enrolled 43 NMOSD patients in two groups: Group 1 (n = 29) received steroids and PE, and Group 2 (n = 14) received steroids with IVIg. The baseline EDSS and ADL scores were recorded and compared with scores at the end of therapy, 4 weeks, and 3 months after. Also, anti-AQP4 antibody was measured at baseline and post-therapy in seropositive patients of both groups. RESULTS: We observed a significant difference in EDSS (p = 0.00) and ADL score (p = 0.00) at day 10 and 3 months in both groups. However, no significant difference in EDSS, as well as ADL score from baseline (p = 0.83; p = 0.25) to 3 months (p = 0.85; p = 0.19), was observed when delta change of score at 3 months was compared across the two groups (p = 0.39; p = 0.52). We observed improved visual acuity in both groups with mild improvement in findings of magnetic resonance imaging at 3 months. We observed a significant decline in AQP4 antibody concentration (at day 10) in group 1 seropositive patients (p = 0.013) with improved EDSS (p = 0.027) and ADL scores (p = 0.026) of these patients. CONCLUSIONS: PE should be considered as a choice of an add-on therapy in anti-AQP4 antibody-positive NMOSD patients compared with IVIg as it is more effective in reducing antibody concentrations.

Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis.

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).