OBJECTIVE: To investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients.
METHODS: This retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, patients that between September 2022 and April 2023 received IVIG as treatment for COVID-19 in the region of Västerbotten, Sweden. We analyzed clinical data, viral load, and anti-SARS-CoV-2 IgG binding and neutralization levels of patient serum samples and IVIG production batches. Primary and secondary outcomes were clinical cure and viral clearance, respectively.
RESULTS: Sixteen patients were analyzed. After a median COVID-19 duration of 4 weeks, a median 60 g IVIG infusion increased SARS-CoV-2 binding and neutralizing antibody levels, with broad in vitro activity against tested variants. The treatment resulted in abrogation of viremia in all patients and general improvement in 15 survivors that all met the primary endpoint. Thirteen patients met the secondary endpoint at follow-up after a median of four months. Two subjects with persistent SARS-CoV-2 carriage relapsed but were successfully retreated with IVIG.
CONCLUSIONS: Antibodies in IVIG efficiently neutralized several SARS-CoV-2 variants. Treatment with IVIG was associated with clinical cure and viral clearance in immunocompromised patients. Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category.

This study aimed to develop and assess the reliability, validity, and sensitivity of the Japanese version of the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract (GIT) Instrument 2.0 (the GIT score), as an evaluation tool for GIT symptoms in systemic sclerosis (SSc). The Japanese version of the GIT score was constructed using the forward-backward method. The reliability and validity of this instrument were evaluated in a cohort of 38 SSc patients. Correlation analysis was conducted to assess the relationship between the GIT score and existing patient-reported outcome measures. Additionally, the sensitivity of the GIT score was examined by comparing GIT scores before and after intravenous immunoglobulin (IVIG) administration in 10 SSc-myositis overlap patients, as IVIG has recently demonstrated effectiveness in alleviating GIT symptoms of SSc. As a result, the Japanese version of the GIT score exhibited internal consistency and a significant association with the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease. Furthermore, the total GIT score, as well as the reflux and distention/bloating subscales, displayed moderate correlations with the EuroQol 5 dimensions (EQ-5D) pain/discomfort subscale and the Short Form-36 body pain subscale. Notably, following IVIG treatment, there was a statistically significant reduction in the total GIT score and multiple subscales. We first validated the Japanese version of the GIT score in Japanese SSc patients in real-world clinical settings. This instrument holds promise for application in future clinical trials involving this patient population.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD.
METHODS: In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated.
RESULTS: Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762-0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value.
CONCLUSIONS: Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.

UNASSIGNED: Myasthenic crisis (MC) is a life-threatening condition for myasthenia gravis (MG). Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) efficaciously treat patients with MC. However, not every MC responds well to rescue therapies, and the determinants for outcome with the evidence from prospective cohorts are still lacking.
UNASSIGNED: To explore the risk factors for in-hospital outcomes in patients with MC.
UNASSIGNED: Using a national neuromuscular center-based cohort of MG with prospective follow-ups from the crisis to the post-crisis phase, we finally included 90 MC episodes from 76 independent patients who received a standard regimen of rescue therapies.
UNASSIGNED: The mean admission age was 52.89 ± 15.72 years. With a female predominance of 63.16% (48/76) and a high proportion of thymoma-associated MG (TMG) of 63.16% (48/76), the overall in-hospital mortality was 2.63% (2/76) and the average duration for mechanical ventilation (MV) use was 17.09 ± 13.36 days (0-53 days). In contrast to the patients with anti-acetylcholine receptor (AChR) antibodies, muscle-specific tyrosine kinase (MuSK)-associated MC exhibited a shorter MV support (5.20 ± 5.07 versus 17.40 ± 13.24 days, p = 0.023), length of intensive care units (ICU) stay (6.00 ± 4.64 versus 19.16 ± 17.54 days, p = 0.046), and hospital stay (16.00 ± 4.12 versus 34.43 ± 20.48 days, p = 0.011). Thymoma [odds ratio (OR): 0.200, 95% confidence interval (CI): 0.058-0.687, p = 0.011], partial pressure of carbon dioxide (PCO2) in blood gas before MV (OR: 1.238, 95% CI: 1.015-1.510, p = 0.035), and pneumonia (OR: 0.204, 95% CI: 0.049-0.841, p = 0.028) were identified as independent risk factors for prolonged MV use. TMG patients with thymoma burden exhibited a notable longer MV use (22.08 ± 17.54 versus 8.88 ± 6.79 days, p = 0.001), a prolonged hospital stay (40.40 ± 26.13 versus 23.67 ± 13.83 days, p = 0.009) compared with non-TMG. Even with complete thymoma resection (R0), TMG exhibited an unfavorable outcome versus non-TMG.
UNASSIGNED: With timely rescue therapies and prospective follow-ups, the in-hospital outcome of MCs was substantially improved. Thymoma, PCO2 in blood gas before MV, and pneumonia were identified as independent risk factors for prolonged MV use.
Risk factors for in-hospital outcome of myasthenic crisis Myasthenic crisis (MC) is a life-threatening condition for myasthenia gravis (MG). Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) efficaciously treat patients with MC. However, not every MC responds well to rescue therapies, and the determinants for outcome with the evidence from prospective cohorts are still lacking. Using a national neuromuscular center-based cohort of MG with prospective follow-ups from the crisis to the post-crisis phase, we were able to include 90 MC episodes from 76 independent patients who received a standard regimen of rescue therapies. The mean admission age was 52.89±15.72 years. With a female predominance and a high proportion of thymoma-associated MG. The overall in-hospital mortality was 2.63% (2/76) and the average duration for MV use was 17.09±13.36 days (0-53 days). In contrast to the patients with anti-AChR antibodies, MuSK-associated MC exhibited a shorter MV support, length of ICU stay and hospital stay. Thymoma, PCO2 in blood gas before MV, and pneumonia were identified as independent risk factors for prolonged MV use. TMG patients with thymoma burden exhibited a notable longer MV use, a prolonged hospital stay compared with non-TMG. Even with complete thymoma resection (R0), TMG exhibited an unfavorable outcome versus non-TMG. With timely rescue therapies and prospective follow-ups, the in-hospital outcome of MCs was substantially improved. Thymoma, PCO2 in blood gas before MV, and pneumonia.

Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study.
ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0-16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16-40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented.
The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4-15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred.
Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors.
ProDERM study (NCT02728752).

Intravenous immunoglobulin (IVIG) is a first-line drug prepared from human plasma for the treatment of autoimmune diseases (AIDs), especially immune thrombocytopenia (ITP). Significant differences exist in protein types and expression levels between male and female plasma, and the prevalence of autoimmune diseases varies between sexes. The present study seeks to explore potential variations in IVIG sourced from distinct sex-specific plasma (DSP-IVIG), including IVIG sourced from female plasma (F-IVIG), IVIG sourced from male plasma (M-IVIG), and IVIG sourced from a blend of male and female plasma (Mix-IVIG). To address this question, we used an ITP mouse model and a monocyte-macrophage inflammation model treated with DSP IVIG. The analysis of proteomics in mice suggested that the pathogenesis and treatment of ITP may involve FcγRs mediated phagocytosis, apoptosis, Th17, cytokines, chemokines, and more. Key indicators, including the mouse spleen index, CD16+ macrophages, M1, M2, IL-6, IL-27, and IL-13, all indicated that the efficacy in improving ITP was highest for M-IVIG. Subsequent cell experiments revealed that M-IVIG exhibited a more potent ability to inhibit monocyte phagocytosis. It induced more necrotic M2 cells and fewer viable M2, resulting in weaker M2 phagocytosis. M-IVIG also demonstrated superiority in the downregulation of surface makers CD36, CD68, and CD16 on M1 macrophages, a weaker capacity to activate complement, and a stronger binding ability to FcγRs on the THP-1 surface. In summary, DSP-IVIG effectively mitigated inflammation in ITP mice and monocytes and macrophages. However, M-IVIG exhibited advantages in improving the spleen index, regulating the number and typing of M1 and M2 macrophages, and inhibiting macrophage-mediated inflammation compared to F-IVIG and Mix-IVIG.

UNASSIGNED: Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking. Here we present efficacy data from ProDERM of IVIg versus placebo for treatment of the cutaneous aspect of DM.
UNASSIGNED: ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label Extension Period (Weeks 16-40), all patients received IVIg for 6 additional cycles. Cutaneous disease was assessed using measures including modified cutaneous DM disease area and severity index activity (CDASI-A) and damage (CDASI-D) scores, and myositis disease activity assessment tool (MDAAT) including visual analogue scale (VAS). This trial is registered with ClinicalTrials.gov, NCT02728752.
UNASSIGNED: The study took place from February 2017 to November 2019. 95 patients received IVIg (N = 47) or placebo (N = 48) in the First Period. Together, 664 IVIg infusion cycles were administered (median dose, 2.0 g/kg). At Week 16, mean CDASI-A change from baseline was -9.36 (95% CI: -12.52, -6.19) in the IVIg group versus -1.16 (-3.32, 0.99) in placebo group (p < 0.0001). At the end of the Extension Period, mean changes from baseline were -10.44 (95% CI: -13.94, -6.94) and -10.03 (-13.12, -6.94), respectively. Similar changes were seen for CDASI-D and VAS of MDAAT. These observations were seen regardless of baseline disease severity.
UNASSIGNED: ProDERM is the first large prospective, randomized trial to demonstrate the efficacy of IVIg to improve the cutaneous manifestations of DM. IVIg treatment significantly improved dermatological symptoms in patients with DM, regardless of disease severity before treatment, suggesting that IVIg is effective for even the most severe cutaneous DM.
UNASSIGNED: This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.

BACKGROUND: Optimal treatment strategy for severe fever with thrombocytopenia syndrome (SFTS) remained unknown. We aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) on SFTS.
METHODS: A retrospective cohort study was conducted based on medical records of the laboratory-confirmed SFTS patients hospitalized during 2010-2020 in the 154th hospital, China. A 1:1 propensity score matching with age, sex, the interval from symptom onset to admission, presence of chronic viral hepatitis, diabetes and disease severity was performed between Non-IVIG group (supportive therapy) and IVIG group (IVIG plus supportive therapy). The matching variables were adjusted to compare the case fatality rates (CFRs), viral load and laboratory parameters between the two groups. Risk ratio (RR) and 95% confidence interval (CI) were reported.
RESULTS: Totally 2219 SFTS patients were recruited. CFRs were significantly higher in 1051 patients in IVIG group than 1168 patients in Non-IVIG group (19.0% vs. 4.6%, RR = 4.30, 95% CI 3.12-5.93). The difference remained significant after matching (17.2% vs. 5.1%, RR = 4.02, 95% CI 2.71-5.97). The CFR of IVIG group was significantly higher in all age groups, two IVIG therapy delay groups and two therapy duration groups compared to that of Non-IVIG group (all P < 0.05). IVIG therapy was related to higher viral loads and reduced counts of lymphocytes, T cells, CD4+ T cells and natural killer cells in the blood (all P < 0.05).
CONCLUSIONS: No obvious efficacy of IVIG in saving life or improving outcome of SFTS was observed. Caution is needed for clinical physicians to continue prescribing IVIG for SFTS patients.
BACKGROUND: Natural Science Foundation of China.

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

OBJECTIVE: To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP.
METHODS: Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment.
RESULTS: Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (P>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (P<0.05).
CONCLUSIONS: The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.
目的: 构建儿童重症腺病毒性肺炎（adenoviral pneumonia，AVP）的风险评分模型，并探讨静脉注射免疫球蛋白（intravenous immunoglobulin，IVIG）治疗重症AVP的合适时机。方法: 回顾性分析1 046例AVP患儿的临床资料，运用多因素logistic回归法建立重症AVP风险预测模型。选取102例AVP患儿验证该模型。再前瞻性纳入75例年龄≤14岁且经该模型判定为有可能发展为重症AVP的患儿，按就诊顺序分为A、B、C 3组，每组各25例。A组：仅予对症支持治疗；B组：除对症支持治疗外，在进展为重症AVP前予IVIG治疗，1 g/(kg·d)，连续2 d；C组：除对症支持治疗外，在进展为重症AVP后予IVIG治疗，1 g/(kg·d)，连续2 d。比较A、B、C 3组治疗后的疗效及相关实验室指标。结果: 年龄<18.5个月、基础病、热程>6.5 d、血红蛋白<84.5 g/L、谷丙转氨酶>113.5 U/L、合并细菌感染6个变量进入重症AVP风险预测模型。该模型的受试者操作特征曲线下面积为0.862，灵敏度为0.878，特异度为0.848。Hosmer-Lemeshow检验显示模型预测值和实际观测值间的一致性较好（P>0.05）。治疗后，B组发热时间和住院时间最短，住院费用最低，治疗有效率最高，并发症发生率最低，白细胞计数最低，白细胞介素（interleukin，IL）-1、IL-2、IL-6、IL-8、IL-10水平最低，肿瘤坏死因子α水平最高（P<0.05）。结论: 该研究构建的重症AVP风险模型对预测重症AVP的发生具有良好的价值；在AVP患儿进展为重症前予IVIG治疗效果更好。.