Intravenous immunoglobulin as clinical immune-modulating therapy.
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ABSTRACT:
SUBMITTER: Gilardin L
PROVIDER: S-EPMC4347774 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
Intravenous immunoglobulin as clinical immune-modulating therapy.
Gilardin Laurent L Bayry Jagadeesh J Kaveri Srini V SV
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20150209 4
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Project description:Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T- and B-cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen-DR isotype [HLA-DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA-DR+CD38+ NK cells and expression of NK cell activation markers CD69 and HLA-DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)-8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA-DR+CD38+ NK cells and plasma IL-8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL-8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage.
| S-EPMC6492477 | biostudies-literature
Project description:ObjectiveTo report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy.MethodsWe retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg.ResultsFive patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19-55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1-10 days). No adverse events related to IVIg were observed.ConclusionsOur preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.
| S-EPMC7543032 | biostudies-literature
Project description:BackgroundLivedoid vasculopathy (LV) is a rare disease characterized by livedo racemosa, atrophie blanche, ulcerations, and severe pain. Low molecular weight heparins and rivaroxaban can be used in LV-patients. In addition, intravenous immunoglobulins (IVIG) have been described as treatment-option.ObjectivesObjective was to investigate the therapeutic effect of IVIG on ulcer, pain and restrictions in daily life.MethodsThirty-two LV-patients who received IVIG at the Department of Dermatology Tübingen between 01/2014 and 06/2019 were identified. Twenty-five of these patients were available for further follow up and were included in the study. Patients were interviewed using a questionnaire focusing on the course of the disease, symptoms, and subjective response to IVIG-treatment.ResultsTwenty-five patients were included in the study (mean follow up: 28.9 months). Patients received an average of 6.8 cycles (range 1-45) of IVIG during the observed period.Significant improvements were seen regarding skin findings, pain, and limitation of daily activities. Complete remission of symptoms was observed in 68% of patients. Good tolerability of IVIG was shown in 92%.ConclusionsA good therapy response regarding ulceration, pain, and daily life restrictions with good tolerability was demonstrated for IVIG (2 g/kg bodyweight over 5 days).
| S-EPMC8474298 | biostudies-literature
Project description:BACKGROUND: Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis. AIMS: To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy. PATIENTS: Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200-300 mg/kg). METHODS: Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay. RESULTS: Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4-1.6 mg/ml. CONCLUSION: Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations and C difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration.
| S-EPMC1891485 | biostudies-other
Project description:IntroductionWe examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD).MethodsAIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder with at least 1 positive seromarker of autoimmunity or at least 2 positive seromarkers by themselves. Three cohorts were studied: (i) retrospective (n = 300), (ii) prospective validation cohort (n = 133), and (iii) treatment cohort (n = 40), administered open-label intravenous immunoglobulin (IVIG).ResultsAIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had autoinflammatory disorder. Significantly more patients with AIM had elevations of C-reactive protein (31% vs 15%, P < 0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% vs 29%; P < 0.001), small fiber neuropathy (20% vs 9%; P = 0.002), and HLADQ8 positivity (24% vs 13%, P = 0.01). Patients with JH/HSD were more likely to have AIM (43% vs 15%, P = 0.001) along with more severe autonomic and gastrointestinal (GI) symptom scores. IVIG treatment was associated with robust improvement in pain, GI, and autonomic symptoms, but adverse events were experienced by 62% of patients.DiscussionAutoimmune markers and autonomic dysfunction are common in patients with unexplained GI symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment, but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov , NCT04859829.
| S-EPMC11524627 | biostudies-literature
Project description:ObjectiveThis is the first double-blind randomized controlled trial evaluating the efficacy and safety of IV immunoglobulin (IVIG) vs placebo in patients with idiopathic small fiber neuropathy (I-SFN).MethodsBetween July 2016 and November 2018, 60 Dutch patients with skin biopsy-proven I-SFN randomly received a starting dose of IVIG (2 g/kg body weight) or matching placebo (0.9% saline). Subsequently, 3 additional infusions of IVIG (1 g/kg) or placebo were administered at 3-week intervals. The primary outcome was a 1-point change in Pain Intensity Numerical Rating Scale score at 12 weeks compared to baseline.ResultsThirty patients received IVIG, and 30 received placebo. In both groups, 29 patients completed the trial. In 40% of patients receiving IVIG, the mean average pain was decreased by at least 1 point compared to 30% of the patients receiving placebo (p = 0.588, odds ratio 1.56, 95% confidence interval 0.53-4.53). No significant differences were found on any of the other prespecified outcomes, including general well-being, autonomic symptoms, and overall functioning and disability.ConclusionsThis randomized controlled trial showed that IVIG treatment had no significant effect on pain in patients with painful I-SFN.Trial registration informationClinicalTrials.gov Identifier: NCT02637700, EudraCT 2015-002624-31.Classification of evidenceThis study provides Class I evidence that for patients with painful I-SFN, IVIG did not significantly reduce pain compared to placebo.
| S-EPMC8205474 | biostudies-literature
Project description:BackgroundAcute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery.MethodsARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively.ResultsThe baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival.ConclusionWe conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support.Trial registrationClinical Trials: NCT02961166; retrospectively registered.
| S-EPMC5827994 | biostudies-literature
Project description:BackgroundIntravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established.MethodsWe conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis.ResultsAmong 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98-6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group.ConclusionIVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.
| S-EPMC8572690 | biostudies-literature
Project description:ObjectiveCoronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking.Methods325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28- and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing.ResultsIn the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients.ConclusionEarly administration of IVIG with high dose improves the prognosis of critical-type patients with COVID-19. This study provides important information on clinical application of IVIG in the treatment of SARS-CoV-2 infection, including patient selection and administration dosage and timing.
| S-EPMC7557105 | biostudies-literature
Project description:BackgroundAbout 10-20% of Kawasaki disease (KD) patients are resistant to the initial infusion of intravenous immunoglobin (IVIG). The aim of this study was to assess whether IVIG resistance in KD patients could be predicted using standard clinical and laboratory features.MethodsData were from two cohorts: a Korean cohort of 7101 KD patients from 2015 to 2017 and a cohort of 649 KD patients from San Diego enrolled from 1998 to 2021. Features included laboratory values, the worst Z-score from the initial echocardiogram or during hospitalization, and the five clinical KD signs at presentation.ResultsFive machine learning models achieved a maximum median AUC of 0.711 [IQR: 0.706-0.72] in the Korean cohort and 0.696 [IQR: 0.609-0.722] in the San Diego cohort during stratified 10-fold cross-validation using significant laboratory features identified from univariate analysis. Adding the Z-score, KD clinical signs, or both did not considerably improve the median AUC in either cohort.ConclusionsUsing commonly measured clinical laboratory data alone or in conjunction with echocardiographic findings and clinical features is not sufficient to predict IVIG resistance. Further attempts to predict IVIG resistance will need to incorporate additional data such as transcriptomics, proteomics, and genetics to achieve meaningful predictive utility.ImpactWe demonstrated that laboratory, echocardiographic, and clinical findings cannot predict intravenous immunoglobin (IVIG) resistance to a clinically meaningful extent using machine learning in a homogenous Asian or ethnically diverse population of patients with Kawasaki disease (KD). Visualizing these features using uniform manifold approximation and projection (UMAP) is an important step to evaluate predictive utility in a qualitative manner. Further attempts to predict IVIG resistance in KD patients will need to incorporate novel biomarkers or other specialized features such as genetic differences or transcriptomics to be clinically useful.
| S-EPMC9934506 | biostudies-literature