Intravenous Immunoglobulin Group Research Articles

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study.

Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Clinical efficacy of prophylactic intravenous immunoglobulin for elderly DLBCL patients with hypogammaglobulinemia in the COVID-19 pandemic era.

Elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergoing reduced intensity R-CHOP therapy are at a heightened risk of acquiring infections, notably coronavirus disease 2019 (COVID-19) infection. This study aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) as prophylaxis against COVID-19 in this vulnerable population. A total of 125 elderly patients with DLBCL undergoing reduced intensity R-CHOP therapy were analyzed in this prospective, multicenter study. Patients with hypogammaglobulinemia were categorized into IVIG and non-IVIG groups, while those with normal immunoglobulin levels constituted the observation group. The study evaluated COVID-19 infection rates, therapy response, and safety outcomes. Among the enrolled patients (median age: 77 years), 89 patients (71.2%) presented with hypogammaglobulinemia at diagnosis, and 56 patients enrolled in the IVIG administration group. IVIG administration remarkably reduced COVID-19 infection rates compared to non-IVIG recipients (8.9% vs. 24.6%; p =0.040). Notably, patients over 80 years old were more susceptible to COVID-19. Patients on IVIG exhibited good tolerance with manageable adverse events. Among patients with hypogammaglobulinemia who received IVIG, 40.5% of patients developed additional immunoglobulin deficiencies during chemotherapy. One or more new hypogammaglobulinemia occurred during chemotherapy in 72% of patients with hypogammaglobulinemia who did not receive IVIG, and in 61.3% of patients who did not have hypogammaglobulinemia at diagnosis. IVIG showed promise in reducing COVID-19 infections among elderly patients with DLBCL receiving reduced intensity R-CHOP therapy. This highlights IVIG's potential as a prophylactic measure, necessitating further investigation to optimize dosing, administration schedules, and potential interactions with vaccination strategies.

Beneficial effects of IVIG treatment on experimental-induced osteoporosis.

Estrogen (E2) plays a significant role in postmenopausal osteoporosis, and its deficiency is related to chronic low-grade inflammation. Intravenous immunoglobulin (IVIG) is composed of immunoglobulins derived from the plasma of healthy donors. Numerous anti-inflammatory pathways are responsible for IVIG's anti-inflammatory action The aim of this study is to investigate the effects of IVIG on experimental-induced osteoporosis. Forty adult female Wistar rats were included in the study. Thirty rats underwent bilateral dorsal ovariectomy. Rats were grouped as Group 1 (n = 10, ovariectomy and saline); Group 2 (n = 10, ovariectomy and E2); Group 3 (n = 10, ovariectomy and IVIG), and Control group (n = 10, no oophorectomy). Histopathological examination of bone tissue, and biochemical analysis for beta-catenin, plasma Tumor Necrosis Factor-α, IL-6, receptor activator of nuclear-κB ligand (RANKL), and osteoprotegerin (OPG) levels were made. The IVIG group had increased trabecular number, area, and thickness with increased bone mineral density as well as decreased trabecular separation compared with the saline group. IVIG group had lower serum RANKL and higher serum OPG levels when compared with the saline group. The bone marrow beta-catenin level was significantly higher in the control and ovariectomy + IVIG groups. IVIG has beneficial effects on experimentally induced osteoporosis with a possible action on inflammation and RANKL-β-catenin pathway.

The mechanism of intravenous immunoglobulin (IVIG) in vascular endothelial injury in kawasaki disease based on neutrophil extracellular traps

This study explores the role of Neutrophil extracellular traps (NETs) in kawasaki disease (KD)-induced vascular inflammatory injury and the protective effect and mechanism of IVIG on vascular endothelial damage. A total of 37 children diagnosed with KD and admitted to Dongguan maternal and Child Health Care Hospital between March 2020 and June 2022 were included in the study. The children were divided into different groups based on their treatment and the presence or absence of coronary artery damage: IVIG treatment group (KDIVIG group), subgroup with coronary artery damage (KDCAL group), and subgroup without coronary artery damage (KDNCAL group), and a Control group consisting of 9 children who underwent surgical treatment. Flow cytometry was used to detect the proportion of neutrophils and the number of NETs in peripheral blood. It was found that the proportion of neutrophils in the peripheral blood of the acute KD group significantly increased with the presence of NETs. RT-PCR and ELISA detection showed that the levels of inflammatory factors TNF-α, IL-6 and CitH3 were abnormally elevated in this acute KD group, and the CAL group exhibited higher proportions of neutrophils and NETs-related markers compared to the NCAL group, while the IVIG group had significantly decreased proportions of neutrophils. PMA culture of neutrophils induced an increase expression of NETs marker protein, the content of NETs cfDNA increased. NETs culture could promote the secretion of TNF-α, whereas IVIG cultured cells inhibited the secretion of TNF-α. Finally, HCAEC cells were cultured with different levels of TNF-α, and the function of HCAEC cells was assessed using CCK8, scratch assay and flow cytometry. The high expression of TNF-α in the NETs group inhibited the proliferation and migration of HUVEC cells and enhanced their apoptosis. In contrast, the IVIG culture group exhibited similar effects to the TNF-α monoclonal antibody, as it inhibited HUVEC cell apoptosis and improved their viability by reducing TNF-α expression. Total protein was extracted from the cells using nano-magnetic beads, and RT-PCR and western blot detection indicated that the increase of TNF-α expression could increase the phosphorylation of NF-κB and and the expression of MMP-9. However, when TNF-α was inhibited by IVIG and TNF-α monoclonal antibody culture, the activity of NF-κB/MMP-9 athway was decreased. Therefore, IVIG may inhibit the production of NETs in KD children, thereby reducing TNF-α/NF-NF-κB/MMP-9 mediated inflammatory response process and protecting the function of vascular endothelial cells.

High-dose intravenous immunoglobulin versus albumin 4% in paediatric toxic shock syndrome: a randomised controlled feasibility study

PurposeToxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent...

Randomized controlled trial of intravenous immunoglobulin for autoimmune postural orthostatic tachycardia syndrome (iSTAND).

This study assesses response to intravenous immunoglobulin (IVIG) in presumed autoimmune postural orthostatic tachycardia syndrome (POTS). POTS may be associated with autoimmune disorders, serum autoantibodies, or recent infection. Uncontrolled case studies suggest that IVIG is beneficial for treating autoimmune POTS. No previous randomized controlled trials have been conducted. This single-site randomized controlled trial compared IVIG with intravenous albumin infusions. Albumin comparator ensured blinding and control for effects of volume expansion. Eligible patients with POTS had COMPASS-31 total weighted score ≥ 40 and met predetermined criteria suggesting autoimmunity. Over 12weeks, participants received eight infusions (0.4gm/kg each). Four infusions were given weekly followed by four infusions every other week. Primary outcome measure was improvement in COMPASS-31 2weeks after final infusion. A total of 50 participants consented; 30 met inclusion criteria and received study drug (16 IVIG and 14 albumin; 29 female). Group baseline characteristics were well matched; 27 participants completed treatment protocol. Change in COMPASS-31 did not differ between groups (median change [IQR]; IVIG: -5.5 [-23.3, 2.5] versus albumin: -10.6 [-14.1, -4.7]; p-value = 0.629). The IVIG group had a higher response rate (46.7% versus 38.5%), but this was not statistically significant. Adverse events were common but usually mild and did not differ between treatment groups. This small randomized controlled trial of IVIG in POTS found no statistical difference in response compared with albumin infusion. Both groups showed improvement possibly related to volume expansion or other effects obscuring group differences. These findings inform development of future immunomodulatory clinical trials in POTS.

Comparison of the oxidative stress status of children with ITP in two therapies using methylprednisolone and methylprednisolone along with IVIG

Background: Idiopathic thrombocytopenic purpura (ITP) is a rare and autoimmune disorder determined by an abnormal reduction in the number of platelets. The current study aims to evaluate the oxidative stress status of children with ITP in two treatment methods using methylprednisolone and methylprednisolone with intravenous immunoglobulin (IVIG).
 Materials and Methods: This retrospective study was conducted on 60 children with ITP who referred to Baghaei Hospital in Ahvaz in 2021. All the ITP children were equally divided into two groups, 30 receiving methylprednisolone and 30 receiving methylprednisolone and IVIG. The sampling of the patients’ blood was done in two stages before and after the start of treatment. Then, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS), total oxidative status (TOS), catalase (CAT) and glutathione were measured according to the instructions in the commercial kit. The analyses were performed using SPSS software version 23. P value < 0.05 was significant.
 Results: The number of platelets after treatment in methylprednisolone and methylprednisolone+ IVIG groups was 133.44 ± 18.93 and 158.76 ± 34.76 (×103/µL), respectively. Itas significantly increased compared to that before the treatment (P = 0.04). The amount of TAC in the group receiving methylprednisolone + IVIG and the methylprednisolone group was 1.64 ± 0.18 and 1.26 ± 0.53 nm, respectively; there was a remarkable difference between the two groups (P = 0.001). Also, SOD, CAT and glutathione in the methylprednisolone + IVIG group were remarkably higher than those in the methylprednisolone group (P < 0.05). Finally, the levels of TOS were lower in the methylprednisolone + IVIG group (19.74 ± 9.93 μmol) than in the methylprednisolone group (26.65 ± 10.64 μmol) (P = 0.01).
 Conclusion: A combination of IVIG and methylprednisolone was found to have a greater effect on improving antioxidant status and decreasing the oxidative stress indices of ITP children.

Risk factors for coronary artery abnormalities and resistance to immunoglobulin plus ciclosporin A therapy in severe Kawasaki disease: subanalysis of the KAICA trial, randomized trial for cicrosporin A as the first-line treatment.

To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with Kawasaki disease (KD) receiving intravenous immunoglobulin (IVIG) plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a phase 3, randomized study (JMA-ILA00174). All data of the patients enrolled in the KAICA trial, who had a Gunma score ≥5 at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including genotypes of KD susceptibility genes were compared between subgroups of patients for CAA or treatment response for each treatment group. Backword-forward stepwise logistic regression analyses were performed. Pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was higher in patients with CAA in both treatment groups and was associated with CAA in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. High serum total bilirubin level was relevant to treatment resistance only in the IVIG plus CsA group (OR = 2.34). Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.

Prednisone Plus Ivig Compared with Prednisone for Immune Thrombocytopenia during Pregnancy

Introduction Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by an isolated low platelet count and is the most common cause of thrombocytopenia during pregnancy, accounting for 1%-4% of thrombocytopenia in pregnant women. Women with ITP who have severe thrombocytopenia are at an increased risk for life-threatening obstetric complications. However, management of ITP during pregnancy can be challenging because treatment choices are limited. Corticosteroids or intravenous immunoglobulin (IVIg) are recommended as first-line treatments for pregnant women with ITP, but the response to initial treatment is approximately 39% and 38%, respectively, lower than that in nonpregnant patients with ITP. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP during pregnancy are urgently needed. Our previous retrospective study revealed an advantage of prednisone combined with IVIg compared to prednisone monotherapy for pregnant patients with ITP. Therefore, the aim of this prospective, randomized, open-label study was to further assess the efficacy and safety of prednisone plus IVIg compared to prednisone monotherapy in pregnant women with ITP. The study has been registered at clinicaltrials.gov. NCT05333744 Methods Eligible treatment-naive ITP patients during pregnancy with a platelet count < 30 × 10^9/L, accompanied by or without bleeding symptoms, were randomly assigned 1:1 to receive prednisone 20 mg per day for 4 weeks plus IVIg 400 mg/kg (total dose ≤20 g per day) for 5 days or prednisone 20 mg monotherapy per day for 4 weeks. Prednisone was gradually tapered to the maintenance dose of 5-10 mg per day until 6 weeks after delivery if there was a response to treatment; otherwise, prednisone was gradually tapered to withdrawal. The primary outcome was overall response (OR), defined as a platelet count ≥ 30 × 10^9/L, a doubling of the baseline platelet count and the absence of bleeding. Secondary endpoints included complete response (CR), time to response, platelet counts at delivery, platelet counts of newborns, and adverse events in parturients. CR was defined as platelet count ≥100×10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding. Results A total of 100 treatment-naive ITP patients during pregnancy were randomly assigned to either the prednisone plus IVIg (n=50) or prednisone monotherapy (n=50) groups. All the baseline characteristics were comparable between the two groups. The median ages of patients in the prednisone plus IVIg group and prednisone monotherapy group were 30.32 years (range, 22-43) and 30 years (range, 28-46), respectively. For patients in the combination and monotherapy groups, the mean estational ages at intervention start were 28.3 weeks and 30.9 weeks, respectively. All patients were followed up for more than 2 months. OR was observed in 23 (46.0%) patients in the combination group and 22 (44%) in the monotherapy group, and no significant difference was observed between the two groups (p=0.91). A significant difference was observed in the time to response between the prednisone plus IVIg group and prednisone monotherapy group (6.14 days vs. 9.84 days, p=0.001). However, the predelivery platelet transfusion of the prednisone plus IVIg group was greater than that of the prednisone monotherapy group. There were no significant differences in the delivery mode between the combined group and monotherapy group. No significant differences were found between the two groups in neonatal outcomes, particularly concerning the neonatal platelet counts. Conclusion Prednisone plus IVIg was an effective and safe treatment for ITP in pregnancy, and this therapy may be a new first-line treatment option for pregnant patients with ITP.

Multicenter, Prospective Study to Investigate the Efficacy and Safety of Intravenous-Immunoglobulin Therapy in Elderly Patients with Diffuse Large B Cell Lymphoma Treated with R-Mini-CHOP

Background The median age at initial diagnosis of DLBCL is estimated to be between the ages of 60 and 70. The number of elderly patients with DLBCL is gradually increasing. But, treatment outcomes of elderly patients were not significantly improved compared to younger patients. Infection is an independent predictor of treatment outcome in patients with DLBCL, and the risk of infection increases with age. The incidence of hypogammaglobulinemia in patients with malignant lymphoma increased from 15% to 39% after rituximab therapy. There was a significant decrease in the occurrence of major infections after intravenous immunoglobulins (IVIG) prophylaxis in hypogammaglobulinemia patients with lymphoproliferative. disorders. In this multicenter prospective study, infection prevention effect and treatment outcomes were identified using IVIG in elderly DLBCL patients with hypogammaglobulinemia who received rituximab combination chemotherapy. Methods In the current study, newly diagnosed DLBCL patients aged 70 years or older who were planning to receive R-mini-CHOP therapy were included. Patients with hypogammaglobulinemia at diagnosis were assigned to the IVIG group. Patients received R-mini-CHOP (rituximab: 375mg/m 2 D1; cyclophosphamide: 400mg/m 2 D1; doxorubicin: 25mg/m 2 D1; vincristine: 1.0mg D1, and prednisolone 40mg/m 2 from D1 to D5), and pegylated G-CSF. After the first cycle of R-mini-CHOP, 400mg/kg of IVIG was administered on D3 and D11. After the second cycle to sixth cycle of chemotherapy, patients received 400mg/kg of IVIG on D11. The primary objective was to evaluate the efficacy of IVIG in reducing severe infections. Grade 3 or 4 infections were defined as severe infections. Results A total of 118 elderly patients were newly diagnosed with DLBCL and were scheduled to receive R-mini-CHOP therapy. Hypogammaglobulinemia was identified in 85 (72.0%) patients. Decreased immunoglobulin D (n=42) and immunoglobulin M (n=39) level were most common, and 18 patients had two or more types of hypogammaglobulinemia at the same time. Fifty-six patients were assigned to the group receiving IVIG. Median age was 77 years (range, 70-90), and 31 (55.4%) were male. In patients who completed R-mini-CHOP and IVIG treatment, complete remission rate was 79.4%. Severe infections of grade 3 or 4 occurred in 3 of 56 (5.4%) patients, and only five (8.9%) patients had COVID-19 infection during the study period. Adverse effects associated with IVIG include fever/chilling, nausea/vomiting which were generally manageable. Only one patient discontinued the study because of chest pain that occurred during IVIG administration. In patients with hypogammaglobulinemia who did not receive IVIG, severe infections occurred in 8 of 29 (27.6%) patients, and COVID-19 infection was developed in 7 of 29 (24.1%). In patients without hypogammaglobulinemia, severe infection occurred in 5 of 33 (15.2%), and COVID-19 infection was developed in 8 of 33 (24.2%) patients. Patients receiving IVIG had a significantly reduced incidence of severe infection compared to patients not receiving IVIG (p=0.028). Furthermore, COVID-19 infection rate during R-mini-CHOP therapy was lower in IVIG receiving patients (p=0.050). Long-term outcomes with relapse rate and survival will be followed up and updated. Conclusion In elderly patients with DLBCL, the combination of R-mini-CHOP and IVIG was safe and effective in preventing infection. In the COVID-19 era, the combination of chemotherapy and IVIG should be considered in elderly DLBCL patients to reduce infection rate and improve treatment outcomes.

Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study

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. ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM received 2.0g/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. 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, 2.0g/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. 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. This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.

Clinical efficacy of immunoglobulin on the treatment of severe fever with thrombocytopenia syndrome: a retrospective cohort study

Optimal treatment strategy for severe fever with thrombocytopenia syndrome (SFTS) remained unknown. We aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) on SFTS. 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. 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). 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. Natural Science Foundation of China.

Immunomodulatory Therapy for MIS-C.

Studies comparing initial therapy for multisystem inflammatory syndrome in children (MIS-C) provided conflicting results. To compare outcomes in MIS-C patients treated with intravenous immunoglobulin (IVIG), glucocorticoids, or the combination thereof. Medline, Embase, CENTRAL and WOS, from January 2020 to February 2022. Randomized or observational comparative studies including MIS-C patients <21 years. Two reviewers independently selected studies and obtained individual participant data. The main outcome was cardiovascular dysfunction (CD), defined as left ventricular ejection fraction < 55% or vasopressor requirement ≥ day 2 of initial therapy, analyzed with a propensity score-matched analysis. Of 2635 studies identified, 3 nonrandomized cohorts were included. The meta-analysis included 958 children. IVIG plus glucocorticoids group as compared with IVIG alone had improved CD (odds ratio [OR] 0.62 [0.42-0.91]). Glucocorticoids alone group as compared with IVIG alone did not have improved CD (OR 0.57 [0.31-1.05]). Glucocorticoids alone group as compared with IVIG plus glucocorticoids did not have improved CD (OR 0.67 [0.24-1.86]). Secondary analyses found better outcomes associated with IVIG plus glucocorticoids compared with glucocorticoids alone (fever ≥ day 2, need for secondary therapies) and better outcomes associated with glucocorticoids alone compared with IVIG alone (left ventricular ejection fraction < 55% ≥ day 2). Nonrandomized nature of included studies. In a meta-analysis of MIS-C patients, IVIG plus glucocorticoids was associated with improved CD compared with IVIG alone. Glucocorticoids alone was not associated with improved CD compared with IVIG alone or IVIG plus glucocorticoids.

High doses of intravenous immunoglobulin stimulate regulatory T cell and suppress natural killer cell in women with recurrent pregnancy loss

The aim was to evaluate whether natural killer (NK) cells and regulatory T (Treg) cells were involved in mechanisms underlying beneficial effects of a high dose of intravenous immunoglobulin (IVIG) on recurrent pregnancy losses (RPL) of unexplained etiology. In a double-blind, randomized, placebo-controlled trial of IVIG (400 mg/kg, for 5 days in 4–6 weeks of gestation) in women with RPL, blood samples were collected pre-infusion, one week after infusion (1 w), and eight weeks of gestation/when miscarried (8 w). Levels of NK and Treg cells in peripheral blood were compared between women with IVIG (n = 50) and placebo (n = 49), and between women with IVIG who gave live birth (n = 29) and those who had miscarriage with normal chromosome (n = 12). Effector Treg cell percentages in IVIG group at 1 w (mean 1.43 % vs. 1.03 %) and at 8 w (1.91 % vs. 1.18 %) were higher than those in placebo group (p < 0.01). Total Treg cell percentages in IVIG group at 1 w (4.75 % vs. 4.08 %) and at 8 w (5.55 % vs. 4.47 %) were higher than those in placebo group (p < 0.05). In women with live birth, total Treg cell percentages increased at 8 w (5.52 %, p < 0.001) compared with pre-infusion (4.54 %) and 1 w (4.47 %), while NK cell activity decreased at 1 w (20.18 %, p < 0.001) compared with pre-infusion (26.59 %). IVIG increased Treg cell percentages and suppressed NK cell activity very early in pregnancy, and these were associated with subsequent live birth. Stimulation of Treg cells and suppression of NK cell activity very early in pregnancy may be a mechanism of pharmacological effects of high dose IVIG.

Plasma exchange (PE) versus intravenous immunoglobulin (IVIG) for the treatment of Guillain-Barré syndrome (GBS) in patients with severe symptoms: A systematic review and meta-analysis.

Guillain- Barré syndrome (GBS) is a neuropathic condition that leads to the rapid development of impairments and is characterized by weakness and numbness or tingling sensation in the legs and arms and sometimes loss of movement and feeling in the legs, arms, upper body, and face. Currently, the cure for the disease is yet to be developed. However, treatment options such as intravenous immunoglobulin (IVIG) and plasma exchange (PE) have been used to minimize the symptoms and duration of the disease. Therefore, this systematic review and meta-analysis compared the efficacy of IVIG and PE in treating GBS patients with severe symptoms. Six electronic databases, including PubMed, Embase, Scopus, ScienceDirect, Medline, and Google scholar, were scoured for articles related and relevant to our research. Additionally, more studies were obtained through the reference lists of the studies retrieved from these electronic databases. Quality assessment and statistical data analysis were conducted using Review Manager software (RevMan 5.4.1). The search for relevant articles resulted in 3253 articles, of which only 20 were included for review in the current study. A sub-group analysis indicated no significant difference in the curative effect (Hughes score reduces by at least one score 4weeks after GBS treatment; OR: 1.00; 95% CI: 0.66-1.52; p=1.00 and Achieving grade 0 or 1 on Hughes scale; OR: 1.03; 95% CI: 0.27-3.94; p=0.97). Similarly, the statistical showed that the difference in length of hospitalization and duration of mechanical ventilation was insignificant between the IVIG and PE group (Standard Mean Difference (SMD): -0.45; 95% CI: -0.92, 0.02; I2=91%; p=0.06 and SMD: -0.54; 95% CI: -1.67, 0.59; I2=93%; p=0.35, respectively). Moreover, the meta-analysis did not find any significant difference in the risk of GBS relapse (RR: 0.47; 95% CI: 0.20-1.14; p=0.10) and risk of complications related to the treatment regimens (RR: 1.03; 95% CI: 0.71-1.48; p=0.89). However, the statistical analysis of outcomes from 3 studies showed that the risk of discontinuation was significantly lower in the IVIG group than in the PE group (RR: 0.22; 95% CI: 0.06-0.88; p=0.03). Our study suggests that IVIG and PE have similar curative effects. Similarly, IVIG seems easier to use and thus can be preferred for treating GBS.

Subcutaneous immunoglobulin therapy for adult patients with primary immunodeficiency disease: Qatar experience.

Subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) are used for the treatment of primary immunodeficiency (PIDD). SCIG is as effective as IVIG in preventing infections.1 However, SCIG has advantages over IVIG as it causes fewer systemic reactions and can be infused at home by the patient leading to improved quality of life.2 Methods: We retrospectively analyzed adult patients with PIDD who received SCIG in an Adult Allergy Clinic in Qatar. Patients who received IVIG before SCIG and are naïve to IgG replacement were included. We compared Serum IgG levels, the number of antibiotic courses received, and the number of hospital admissions one year before and one year after starting SCIG. SF36 score was used to compare health-related quality of life scores before SCIG and after one year of SCIG. Twenty patients were included in the study, of which 17 were on prior IVIG replacement, and three were naive to replacement. SCIG replacement resulted in the maintenance of serum IgG levels in those who received IVIG prior. SCIG resulted in a statistically significant reduction in the number of antibiotics prescribed and hospitalization in the naïve subgroup but no substantial change in the prior IVIG group. 6/20 patients developed side effects like injection site pain, swelling, and headache. No patients developed significant systemic side effects. 10/20 patients discontinued the SCIG therapy, four patients due to side effects, and others due to noncompliance and financial reasons. SF36 Score was compared for the five patients in IVIG prior group and showed no significant improvement in individual score but improvement in the overall score (p=0.003) Conclusions: In our experience, SCIG therapy effectively prevents recurrent infection in PIDD patients, and patients did not experience any significant systemic side effects. There is a substantial improvement in the quality of life. However, compliance continues to be a problem.

Efficacy and Safety Analysis of Combination Therapy Consisting of Intravenous Immunoglobulin and Corticosteroids versus Respective Monotherapies in the Treatment of Relapsed ITP in Adults.

Objective In this study, we aimed to evaluate the efficacy and safety of combination therapy, consisting of intravenous immunoglobulin (IVIg) and corticosteroids, in comparison to respective monotherapies in the treatment of relapsed immune thrombocytopenia (ITP) in adults. Methods A retrospective analysis of clinical data was conducted on 205 adult patients with relapsed ITP who received first-line combination therapy or monotherapy in multiple centers across China from January 2010 to December 2022. The study evaluated the patients' clinical characteristics, efficacy, and safety. Results We found that the proportion of patients with platelet counts in complete response was significantly higher in the combination group (71.83%) compared with the IVIg group (43.48%) and the corticosteroids group (23.08%). The mean PLT max in the combination group (178 × 10 9 /L) was significantly higher than that in the IVIg group (109 × 10 9 /L) and the corticosteroids group (76 × 10 9 /L). Additionally, the average time for platelet counts to reach 30 × 10 9 /L, 50 × 10 9 /L, and 100 × 10 9 /L in the combination group was significantly shorter than in the monotherapy groups. The proportion curves for reaching these platelet counts during treatment were also significantly different from those in the monotherapy groups. However, there were no significant differences in the effective rate, clinical characteristics, and adverse events among the three groups. Conclusion We concluded that combining IVIg and corticosteroids was a more effective and faster treatment for relapsed ITP in adults than using either therapy alone. The findings of this study provided clinical evidence and reference for the use of first-line combination therapy in the treatment of relapsed ITP in adults.

Clinical features and real-world outcomes of Guillain–Barré syndrome in the Philippines (P11-8.010)

<h3>Objective:</h3> We aimed to determine the profile of Guillain–Barré syndrome (GBS) in the Philippines, compare the outcomes who received intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE), and determine the factors related to prolonged hospital stay/late motor recovery. <h3>Background:</h3> There is a substantial deficiency of representative data in the literature on the profile and outcomes of GBS in the Philippines. <h3>Design/Methods:</h3> We conducted a retrospective cohort study of adult GBS patients admitted to the Philippine General Hospital from 2009 to 2019. <h3>Results:</h3> We included 105 patients with confirmed GBS diagnoses. The predominant variant was acute inflammatory demyelinating polyneuropathy (n = 40, 38.1%). The median time to onset of motor recovery was 13 days, while the median hospital stay was 15 days. The difference in outcomes of patients in the IVIg (n = 44) and TPE (n = 24) groups (walking with aid/GBS-disability scores/ventilator dependency at 1 month, duration dependent on the ventilator, intensive care unit stay, and hospital stay) were not statistically significant, except for mild disability at 1 month (p = 0.009). Pneumonia (crude odds ratio (OR) 7.85, 95% CI 2.89–21.33, p &lt; 0.001; adjusted OR 5.65, 95% CI 1.59–20.05, p = 0.007), urinary tract infection (crude OR 6.5, 95% CI 1.39–30.47, p = 0.008; adjusted OR 15.62, 95% CI 1.80–135.82, p = 0.013), and dysautonomia (crude OR 3.60, 95% CI 1.31–9.91, p = 0.01) were significantly related to a prolonged hospital stay. Considering only the treatment groups, the hazard ratio (HR) for late onset of motor recovery comparing IVIg and TPE was 0.75 (95% CI 0.31–1.85, p = 0.533) which was not not statistically significant; after adjusting for age and sex, the HR remained insignificant (0.69, 95% CI 0.27–1.74, p = 0.429). <h3>Conclusions:</h3> Our study presented the first comprehensive information regarding the features and outcomes of GBS patients in the Philippines. <b>Disclosure:</b> Dr. Espiritu has nothing to disclose. Dr. Separa has nothing to disclose. Dr. Milla has nothing to disclose. Dr. Adiao has nothing to disclose. Carl Froilan Leochico has nothing to disclose. Roland Dominic Jamora has received personal compensation in the range of $500-$4,999 for serving as a Consultant for torrent. Roland Dominic Jamora has received research support from CCXDP.

Effects of intravenous immunoglobulin on the negatively transformed subpopulations of neutrophilic granulocytes in newborns with congenital pneumonia and neonatal sepsis

Today, the diagnosis and treatment of severe infectious and inflammatory diseases in newborns, e.g., congenital pneumonia (CP) and neonatal sepsis (NS), present difficult problems. Searching sensitive and specific severity markers of bacterial inflammatory process as well as early and effective treatment are crucial for the outcome and prognosis of these life-threatening diseases. The aim of our study was to assess the effects of intravenous immunoglobulin (IVIG) injections on the negatively transformed subpopulations of neutrophilic granulocytes (NG) СD64-CD16+СD32+СD11b+, СD64+CD16+СD32+СD11b+ and evaluation of their functional activity in newborns with CP and NS. We have observed 38 full-term newborn patients. Group 1 included 19 infants with CP, including 11 children who received conventional therapy and IVIG (group 1.1), and 8 children treated at conventional protocols (group 1.2). Group 2 included 19 children with NS, including 12 children who underwent conventional therapy and IVIG treatment (group 2.1), and 7 children who were subject to conventional therapy (group 2.2). The comparison group consisted of 22 healthy full-term newborns. Testing of NG population included the following parameters: counting the numbers of NG subpopulations which simultaneously expressed CD11b CD64, CD32, CD16, as well as their phenotypic patterns, with regard of the receptor expression density (MFI) using flow cytometric techniques. Moreover, we determined phagocytic and microbicidal activity of the granulocytes. We have revealed negative transformation of СD64-CD16+СD32+СD11b+ and СD64+CD16+СD32+СD11b+ subpopulations of neutrophilic granulocytes in newborns with CP and NS, The diagnostic significance of increased СD64+CD16+СD32+СD11b+NG subpopulation was more pronounced with increasing severity of bacterial infection and inflammatory process, i.e., 18.7-fold in CP, 52.3-fold in NS, along with predominant decrease in expression of appropriate membrane receptors. These phenotypic changes were associated with impaired phagocytic and killing activity of NG. The effect of IVIG on the impaired mechanisms of antibacterial immunity is associated not only with alleviation of IgG deficiency, but also with positive remodeling of negatively transformed subpopulations of СD64-CD16+СD32+СD11b+NG and СD64+CD16+СD32+СD11b+NG, improved effector functions of NG, especially in cases of CP. Thus, following IVIG treatment, a reduced number of СD64-CD16+СD32+СD11b+NG subpopulations was fully recovered in CP, while it increased 1.5 times in NS, and the content of diagnostically significant СD64+CD16+СD32+СD11b+NG subpopulation showed a significantly decrease, both in CP (2-fold) and in NS (2.6-fold). However, this index remained higher than the content of this subpopulation in healthy newborns. At the same time, we have noted the restorative or modulatory effects by changing density of trigger molecules in NG subpopulations. Limitation of the negative NG transformation in their functionally significant subpopulations in newborns with CAP and NS was accompanied by positive clinical effects, i.e., optimization of antibiotic therapy, reduced duration of treatment, and improved mortality rates.

Adjuvant intravenous immunoglobulin administration on postoperative critically ill patients with secondary peritonitis: a retrospective study.

The use of intravenous immunoglobulin (IVIG) in sepsis patients from bowel perforation is still debatable. However, few studies have evaluated the effect of IVIG as an adjuvant therapy after source control. This study aimed to analyze the effect of IVIG in critically ill patients who underwent surgery due to secondary peritonitis. In total, 646 medical records of surgical patients who were treated for secondary peritonitis were retrospectively analyzed. IVIG use, initial clinical data, and changes in Sequential Organ Failure Assessment (SOFA) score over the 7-day admission in the intensive care unit for sepsis check, base excess, and delta neutrophil index (DNI) were analyzed. Mortalities and periodic profiles were assessed. Propensity scoring matching as comparative analysis was performed in the IVIG group and non-IVIG group. General characteristics were not different between the two groups. The survival curve did not show a significantly reduced mortality in the IVIG. Moreover, the IVIG group did not have a lower risk ratio for mortality than the non-IVIG group. However, when the DNI were compared during the first 7 days, the reduction rate in the IVIG group was statistically faster than in the non-IVIG group (P<0.01). The use of IVIG was significantly associated with faster decrease in DNI which means faster reduction of inflammation. Since the immune system is rapidly activated, the additional use of IVIG after source control surgery in abdominal sepsis patients, especially those with immunocompromised patients can be considered. However, furthermore clinical studies are needed.