Role Of Intravenous Immunoglobulin Research Articles

The Role of Intravenous Immunoglobulin (IVIG) in Reducing Infection Risk in Multiple Myeloma (MM) Patients Receiving Immune-Based Therapies: A Single Center Experience

Introduction Immune-based therapies, including the anti-CD38 antibody daratumumab (Dara), and most recently bispecific antibodies (BsAb) targeting CD3 and BCMA, GPRC5D or FCRH5 are increasingly important strategies used to treat Multiple Myeloma. However, there are concerns that the prolonged use of these therapies predisposes patients (pts) to increased rates of infection, partly due to hypogammaglobulinaemia. To this date, most clinical trials on Dara and BsAb do not consistently capture rates of hypogammaglobulinaemia and leaves the use of intravenous immunoglobulin (IVIg) as prophylaxis to individual investigator discretion. There are currently a paucity of studies documenting IVIg as a means to reduce infection risk in these pts. Patient and Methods All patients with MM who started Dara or BsAb therapy at St Vincent's Hospital Melbourne from Jan 2021 to Dec 2022 were included in this retrospective chart review. Patients who received more than 2 months of treatment were included. The evaluation period for each patient began at the time of first Dara or BsAb dose and ended at the cut-off date of 28 th June 2023. The two time periods were “ON IVIg” defined as any time within 30 days of last IVIg administration and “OFF IVIg” defined as any time >30 days from last IVIg administration. The primary outcome was the incidence rate of all grade infections (expressed in events/person-year) during periods of ON IVIg vs OFF IVIg. Secondary outcomes included incidence rate of severe infection (CTCAE Grade 3-5). Incidence rate ratios (IRR) and the corresponding 95% confidence intervals were calculated using the Exact Poisson method. Results A total of 52 Dara or BsAb treated pts were identified of which 7 were excluded due to treatment cessation from progressive disease within 2 months. The remaining 45 pts were included in the study of which 16 were on Dara, 16 on a BCMA BsAb and 13 on a non-BCMA BsAb. All 16 of the patients on Dara received Dara as a triplet combination. Median age was 65 (IQR 59-70), 25 (56%) were male and median prior lines of therapy received was 1 (IQR 1-3). At the start of treatment, 34 pts (76%) had documented hypogammaglobinaemia of which 12 (27%) had severe hypogammaglobinaemia (defined uninvolved IgG <4.0 g/L). Median functional IgG was 5.0 g/L (IQR 3.9-6.5). Eleven pts (24%) were already on IVIG prior to Dara or BsAb therapy and a further 18 (40%) were commenced on IVIG during the course of treatment. At the cut-off date, 30 (67%) pts were still receiving Dara or BsAb therapy. Median time on treatment was of 8.94 months (IQR 5.06-14.30). The proportion of time ON IVIg for the cohort was 53%. Patient receiving BsAb spent a greater proportion of time ON IVG than patients receiving Dara-based therapy (56% vs 42%, p <0.002). There were 95 all grade infections during the evaluated period, most commonly in the respiratory tract; upper respiratory tract infections (36%), lower respiratory tract infections (31%) and COVID-19 (12%). There were 15 documented severe infections of which 10 occurred during the OFF IVIG period. There were no infection related deaths. The median time to first infection from commencement of Dara or BsAb was 3.12 (IQR 1.25-5.61) months. The rate of all grade infections ON IVIG was 1.54 (95% CI 1.07-2.15) per person years and lower compared to 2.56 (1.95-3.29) per person years OFF IVIG with IRR of 0.60 (95% CI 0.39-0.93; p=0.016) (figure 1). Rate of severe infections was 0.22 (0.07-0.51) and 0.43 (0.20-0.78) per person years respectively with IRR of 0.52 (0.14-1.66; p=0.234). BsAb therapy had a higher all grade infection rate vs Dara-based therapy; 2.86 (2.23-3.62) vs 1.39 (0.91-2.03) per person years respectively; IRR 2.06 (1.30-3.38; p=0.001) Conclusion There are high rates of pre-existing hypogammaglobinaemia in MM patients even during early lines of treatment. The use of IVIG during immune-based therapies appears to significantly reduce the yearly rate of all grade infections by 40% in our cohort. Differences between the rates of severe infection ON IVIg and OFF IVIg are not significant due to small number of events. Further prospective studies are needed to confirm these findings, towards an evidence-based approach in IVIg support for patients with myeloma on novel immunotherapies.

Intravenous Immunoglobulin in Kawasaki Disease-Evolution and Pathogenic Mechanisms.

Kawasaki disease (KD) is an acute vasculitis of childhood that affects the medium vessels with a special predilection to the involvement of coronary arteries. The major morbidity of this disease is due to coronary artery aneurysm, which occurs in about 25-30% of untreated cases. For decades now, intravenous immunoglobulin (IVIg) has consistently been shown to reduce the risk of CAAs to less than 5%. However, the mechanism of immunomodulation remains unclear. Several studies on the role of IVIg in the modulation of toll-like receptor pathways, autophagy, and apoptosis of the mononuclear phagocytic system, neutrophil extracellular trap, and dendritic cell modulation suggest a modulatory effect on the innate immune system. Similarly, certain studies have shown its effect on T-cell differentiation, cytokine release, and regulatory T-cell function. In this review, we discuss the potential mechanisms underlying the immunomodulatory actions of IVIg in patients with Kawasaki disease. Furthermore, we provide a summary of the evidence regarding various infusion protocols and dosages utilized in the treatment of KD patients.

Role of IVIg in Severe Neonatal Jaundice due to Isoimmunization A Retrospective Cohort Study

Aim To see the efficacy of intravenous immunoglobulin (IVIg) in reducing the need for exchange transfusion (ET) in neonates with isoimmune hemolytic disease with serum bilirubin at or above exchange level. Methods Retrospective cohort study conducted in neonatal intensive care unit of a tertiary care center from March 2015 to February 2020 included neonates with gestational age ≥35 weeks with positive Direct Coombs Test with serum bilirubin at or above exchange level according to American Academy of Pediatrics charts with no bilirubin encephalopathy at presentation. Study subjects were followed till discharge. Results ET was prevented in 8/41 (19.5%) cases who received IVIg initially vs. 2/51 cases (3.92%) who didn’t ( P = .02, relative risk: 1.98 with 95% confidence interval [1.32-2.98] with number needed to treat: 2.51). Total duration of phototherapy was significantly lesser in those receiving IVIg ( P < .0001). Conclusion Targeted use of IVIg in isoimmune hemolytic disease of newborn with serum bilirubin rising despite intensive phototherapy or within 2 to 3 mg/dL of the exchange level is more likely to benefit than harm and remain prudent.

Interpretation of "International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn"

International guidelines regarding the role of intravenous immunoglobulin (IVIG) in the management of Rh- and ABO-mediated haemolytic disease of the newborn was drafted by an international panel of experts in the fields of hematology, neonatology, and blood transfusion and was published in British Journal of Haematology on March 16, 2022. The guidelines summarize the evidence-based practice of IVIG in Rh- and ABO-mediated haemolytic disease of the newborn and propose related recommendations. The guidelines recommend that IVIG should not be applied as a routine treatment regimen for Rh- and ABO-mediated haemolytic disease of the newborn in order to reduce exchange transfusion (ET), and the best time to apply IVIG remains unclear in the situations where hyperbilirubinaemia is severe (approaching or exceeding the ET threshold) or ET cannot be implemented. These guidelines are formulated with rigorous methods, but with the lower quality of evidence.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence‐based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO‐mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody‐mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High‐quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

The Role of Intravenous Immunoglobulin in Decreasing the Level of Procalcitonin in Early Phase of Sepsis: A Prospective Study

The Role of Intravenous Immunoglobulin in Decreasing the Level of Procalcitonin in Early Phase of Sepsis: A Prospective Study

Higher levels of IgA and IgG at sepsis onset are associated with higher mortality: results from the Albumin Italian Outcome Sepsis (ALBIOS) trial

BackgroundThe role of intravenous immunoglobulins (IVIG) during sepsis is controversial, as different trials on IVIG have observed inconsistent survival benefits. We aimed to elucidate the possible association and clinical significance between circulating levels of immunoglobulins.MethodsIn a subset of 956 patients with severe sepsis and septic shock of the multicentre, open-label RCT ALBIOS, venous blood samples were serially collected 1, 2, and 7 days after enrolment (or at ICU discharge, whichever came first). IgA, IgG and IgM concentrations were assayed in all patients on day 1 and in a subgroup of 150 patients on days 2 and 7. Ig concentrations were measured employing a turbidimetric assay, OSR61171 system.ResultsIgA on day 1 had a significant predictive value for both 28-day and 90-day mortality (28-day mortality, HR: 1.50 (95% CI 1.18–1.92); 90-day mortality, HR: 1.54 (95% CI 1.25–1.91)). IgG, but not IgM, on day 1 showed similar results for 28-day (HR 1.83 (95% CI 1.33–2.51) and 90-day mortality HR: 1.66 (95% CI 1.23–2.25)). In addition, lower levels of IgG but not of IgA and IgM, at day 1 were associated with significantly higher risk of secondary infections (533 [406–772] vs 600 [452–842] mg/dL, median [Q1–Q3], p = 0.007).ConclusionsIn the largest cohort study of patients with severe sepsis or septic shock, we found that high levels of IgA and IgG on the first day of diagnosis were associated with a decreased 90-day survival. No association was found between IgM levels and survival. As such, the assessment of endogenous immunoglobulins could be a useful tool to identify septic patients at high risk of mortality.Trial registration #NCT00707122, Clinicaltrial.gov, registered 30 June 2008

The role of intravenous immunoglobulin in treatment of refractory Felty syndrome c

The role of intravenous immunoglobulin in treatment of refractory Felty syndrome c

Is there a Role of Intravenous Immunoglobulin in Immunologic Recurrent Pregnancy Loss?

Recurrent pregnancy loss (RPL) commonly refers to three or more miscarriages that occur before 20 weeks of pregnancy. The immunological cause of RPL could be either an auto- or alloimmune-related event or both. Because of the discovery of immunological abnormalities in RPL patients in clinical practice, several immunomodulatory therapies were introduced to maintain the immune balance at the maternal-fetal interface. Intravenous immunoglobulin (IVIg) is one of the immunomodulators. In recent years, several studies have analyzed the therapeutic effect of IVIg on RPL patients with antiphospholipid syndrome (APS) or unexplained RPL. However, their results are controversial. IVIg can be used in RPL patients with APS who have previously failed in other treatments. It is recommended that IVIg infusion could be considered used before conception in RPL patients who have cellular immune abnormalities such as increased natural killer (NK) cell counts, NK cell cytotoxicity, or increased T helper (Th)1/Th2 ratio, depending on the cut-off values of each hospital. The aim of this review was to summarize the mechanisms, efficacy, pharmacokinetics, and side effects associated with passive immunization using IVIg in immunologic RPL, according to the literature published in recent years. We hope that more obstetricians will be able to understand the timing and indication of IVIg properly in immunologic RPL patients and effectively enhance pregnancy outcomes for mothers and neonates.

The Role of Intravenous Immunoglobulins in Treatment of Viral Encephalitis in Children

The Role of Intravenous Immunoglobulins in Treatment of Viral Encephalitis in Children

Beta-Hemolytic Streptococci and Necrotizing Soft Tissue Infections.

β-hemolytic streptococci are major causes of necrotizing soft tissue infections (NSTIs), Streptococcus pyogenes (group A streptococcus; GAS) in particular. NSTIs caused by Streptococcus dysgalactiae (SD) have also been reported. In the INFECT cohort of 409 NSTIs patients, more than a third of the cases were caused by GAS (31%) or SD (7%). Risk factors of streptococcal NSTIs compared to streptococcal cellulitis have previously been largely unknown. The INFECT study confirmed blunt trauma as an important risk factor. In addition, absence of pre-existing skin lesions and a lower BMI were associated with NSTIs. The study also confirmed that septic shock is more frequent in GAS cases than in other types of NSTIs. Septic shock was also among several predictors of mortality. The role of intravenous immunoglobulin (IVIG) in streptococcal NSTIs has been unclear. In the INFECT cohort, IVIG treatment was associated with increased survival. As in other studies, a significant microbial diversity was observed, but with predominance of a few emm types. Overall, the INFECT study gives a comprehensive and contemporary picture of the clinical characteristics and the microbes involved in streptococcal NSTIs. The reported severity of disease underscores the need for new efforts aimed at identifying novel diagnostic measures and improved treatment.

P253 ROLE OF HYPOGAMMAGLOBULINEMIA AND INTRAVENOUS IMMUNOGLOBULIN IN OUTCOMES FOR PATIENTS THAT HAVE UNDERGONE LUNG TRANSPLANTATION

The effect of hypogammaglobulinemia on post-transplant outcomes and the role of intravenous immunoglobulin (IVIG) in patients who have undergone lung transplant is unknown. No guidelines have been established for the use of IVIG in patients who have undergone solid organ transplantation.

MON-168 A CASE REPORT OF HUMAN PARVOVIRUS B19 INFECTION IN A RENAL TRANSPLANT PATIENT

Anaemia after kidney transplant has been linked to infection by Parvovirus (PV) B19. Organ transplant patients can have the B19 virus persisting for years due to impairment of the neutralizing antibody response and/or cellular immunity. Up to 39% of kidney transplant (KT) recipients suffer from chronic anaemia. They may acquire symptomatic PV B19 infection from the donor, the community or from reactivation of endogenous latent or persistent virus. PV B19 infection in KT recipients tend to occur within a 6-month period after transplantation when the immuno-suppression (IS) is at the strongest. This case report describes a 49 year old Malay lady who has End Stage Renal Disease secondary to Systemic Lupus Erythematosus. She was on haemodialysis for 17 years before a deceased donor renal transplant in November 2017. Thymoglobulin was used as her induction agent and maintained with mycophenolate sodium (Myfortic) at 360 mg bd, tacrolimus and prednisolone. Her tacrolimus level ranges from 8 to 10 ng/ml. Her baseline haemoglobin (Hb) prior to the renal transplant was 9.7 g/dL. Post operation Hb ranging from 8.5 to 9 g/dL. Iron studies showed adequate iron stores with ferritin and transferrin saturation level of 770ug/L and 93% respectively. There was no evidence of hemolysis and the reticulocyte was 0.19%. Subcutaneous(SC) erythropoietin stimulating agent ( ESA) was started 2 weeks post operation to maintain her Hb level. Despite regular SC ESA injection, her Hb level did not improve and dropped 6 weeks after the operation and became pancytopenia. Her serum creatinine was 180 umol/L. SLE activity markers were negative . Pre-transplant immunoglobulin G (IgG) studies showed positivity to Cytomegalovirus (CMV). For the next 4 months, she required 3 to 4 pints of Red Blood Cells (RBC) transfusions monthly. Oesophagogastroduodenoscopy(OGDS) showed gastric erosion only. CMV PCR sent repeatedly were negative. In May 2018, Parvovirus PCR was found to be positive with positive IgG and negative IgM level. Bone marrow aspiration and trephine (BMAT) showed normo-cellular marrow spaces. Granulopoiesis was present with all stages of maturation seen. Megakaryocytes was morphologically unremarkable. Erythropoieisis was preserved. There were a few intranuclear inclusions seen. The intranuclear inclusions were suggestive of Parvovirus infection ( Figure 1). She received intravenous immunoglobulin (IVIg) with 2g/kg in total. Her Hb level was successfully maintained above 10g/dL without further RBC transfusion. WCC and platelet counts also normalized. Her immunosuppression was changed to combination of everolimus, tacrolimus and prednisolone. Parvovirus PCR in June and July 2018 were consequently negative. In October 2018 her Hb level started to drop again. Repeated Parvovirus PCR taken was positive and she was given IVIg again and responded to treatment. She was discharged to her hometown hospital with close monitoring of Parvovirus PCR and Hb level. Figure 1: Intranuclear inclusions in BMAT This case report suggests the importance of including parvovirus B19 infection in the differential diagnosis of persistent anaemia in organ transplant patients and the need to monitor the PCR closely for reactivation and the role of IVIg with reduced IS as part of the management.

NK cell frequency and cytotoxicity in correlation to pregnancy outcome and response to IVIG therapy among women with recurrent pregnancy loss.

Recurrent miscarriage (RM) has a multifactorial etiology mainly due to chromosomal abnormalities and immunological factors. Treating RM has remained to be a challenging issue and the role of intravenous immunoglobulin (IVIG) in treating RM is still controversial. This study aimed to evaluate the changes in natural killer (NK) cells' frequency and cytotoxicity in patients with RM who received the IVIG therapy. A total of 78 women with a history of three or more recurrent miscarriages were included and their peripheral blood was drawn in case of positive pregnancy test. On the same date, 400 mg/kg of IVIG was administrated intravenously in 38 women and it continued every four weeks through weeks 30-32 of gestation. The remaining 40 patients with RM were included to be the untreated control group. Then, the effects of IVIG on NK cell frequency, cytotoxic activity, and the expression of inhibitory and activating receptors in the patients with RM, pre and posttreatment were assessed. NK cells percentage and cytotoxicity were significantly reduced in the IVIG-treated patients after 32 weeks of gestation (p < 0.0001). Expression levels of inhibitory receptors was increased, however, the expression levels of activating receptors were significantly decreased after the IVIG therapy. Pregnancy outcome after the treatment was significantly higher (86.8%) in the IVIG-treated patients than controls (45%; p = 0.0006). Our results suggested that women with RM may benefit from IVIG as a therapeutic approach and the frequency and functional status of peripheral NK cells may serve as a valuable predictive factor of therapy response.

Role of intravenous immunoglobulin as immuno-resuscitative therapy in severe dengue with hyperferritinemic multi-organ dysfunction syndrome : A single centre experience

Role of intravenous immunoglobulin as immuno-resuscitative therapy in severe dengue with hyperferritinemic multi-organ dysfunction syndrome : A single centre experience

Role of intravenous immunoglobulin in the treatment of Kawasaki disease.

Intravenous immunoglobulin (IVIg) is a purified plasma product that is used for many immune-deficient conditions and autoimmune conditions. Use of IVIg for treatment for Kawasaki disease (KD) is critical for control of inflammation. The American Heart Association (AHA) recommends a single infusion of 2 g/kg preferably given during the first 10 days of illness. In this review, we have discussed the possible mechanisms of action of IVIg in KD and its clinical usage in this condition.

Intravenous immunoglobulin as monotherapy for myasthenia gravis during pregnancy

IntroductionPregnant women with myasthenia gravis (MG) are at increased risk of complications and adverse outcomes, including the teratogenic effects of many drugs used to treat MG women of childbearing age. The effectiveness of intravenous immunoglobulins (IVIg) on other autoimmune mediated diseases has been extensively reported in recent years, although little is known about the role of IVIg in the treatment of MG during pregnancy. We designed this study to determine the effectiveness of IVIg as monotherapy during pregnancy for women with MG. Material and methodsFive pregnant MG patients (mean age at delivery 36.4years, SD 5.8, range 29.4–45.2) were studied in 2013–14. Their treatment was switched to monthly IVIg cycles 2months before the pregnancy. Follow-up included monthly neurological QMG throughout the pregnancy and postpartum, obstetrical monitoring during monthly visits in the first two trimesters of the pregnancy, fortnightly visits between week 32 and week 36, and weekly visits after 36weeks, and neonatal follow-up after delivery. ResultsWe observed no exacerbations during pregnancy, delivery or post-partum. The mean QMG score at baseline (before pregnancy) was 7.4 points in five women with generalized forms of MG. The maximum mean value reached during pregnancy was 8.6 points. The mean pregnancy duration was 38 w+5 d. No infant with transient neonatal myasthenia gravis. ConclusionsThese results suggest that monotherapy with IVIg during pregnancy in MG patients could be promising, although confirmation is required in studies with larger populations.

Sub-acute Sclerosing Pan-encephalitis in a 5 Years Old Child: A Response to Intravenous Immunoglobulin and Steroids

A five years old Yemeni boy presented with a 5 months history of progressive neurological deterioration in picture of progressive cognitive decline , seizures and hyperkinetic movements. Patient came from an area with political instability and low socio-economic status. There was history suggestive of measles at 2 years of age. He never received measles vaccination. Diagnosis of sub acute sclerosing pan encephalitis (SSPE) was made based on clinical symptoms, serum and CSF findings of high measles IgG, neuroradiological findings as well as neurophysiological findings. We report this case to highlight the role of intravenous immunoglobulin and steroid in improving his symptoms.

Intravenous Immunoglobulin in the Treatment of Primary Immunodeficiency Diseases.

Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.].

A Role of Intravenous Immunoglobulin in Human Parechovirus Type 3 Infection in an In Vitro Model

A Role of Intravenous Immunoglobulin in Human Parechovirus Type 3 Infection in an In Vitro Model