Association Between IL-23 And Coronary Arterial Lesions In Children With Kawasaki Disease

The pathogenesis of coronary artery lesions (CALs) in KD patients has been thought of as an unknown stimulus that triggers an inflammatory cascade with activation of the immune system. However, interleukin-23 (IL-23) is supposed as a key cytokine in inflammatory and autoimmunity diseases. The role of IL-23 in the pathogenesis of CALs has not been fully elucidated. This study explored the relationship between the serum IL-23 levels and CALs in patients with KD. We collected blood specimens from 90 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-23, IL-6, IL-17A, IL-10, MCP-1 and VEGF were measured in 190 cases, including 4 groups: KD with CALs (n = 46), KD without CALs (n = 44), febrile control group, (FC, n = 40) and normal control group, (NC, n = 60). Clinical parameters were tested in all subjects. IL-23 was significantly elevated in the KD group compared with the febrile and normal control groups, especially increased in the KD patients with CALs. Serum levels of IL-23 in KD patients were positively associated with WBC, CRP, IL-6, IL-17A, IL-10, MCP-1, and VEGF in children with KD. IL-23 may be involved in the pro-inflammatory process and the pathogenesis of CALs in KD patients.

Patient and Clinical Factors at Admission Affect the Levels of Neutralizing Antibodies Six Months after Recovering from COVID-19

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAbhigh, n = 153) and low (NAblow, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAblow group, a larger proportion of the NAbhigh group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) μg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO2 levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657–0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.

Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukaemia patients with hypogammaglobulinaemia and infection; analysis of total national utilisation data in Australia 2008-2013

Objectives To analyse total national utilisation of immunoglobulin (Ig) replacement therapy (IgRT) for Chronic Lymphocytic Leukaemia patients with acquired hypogammaglobulinaemia and severe and/or recurrent bacterial infections. Methods In 2007, the National Blood Authority first published Criteria for the clinical use of intravenous immunoglobulin in Australia. The Australian Red Cross Lifeblood assessed, approved, and recorded all supply with patient demographics, distribution data, intravenous Ig (IVIg) volumes and treatment episodes. IVIg was the sole product used in Australia from 2008-2013 inclusive. Results From 2008-2013 across Australia, 2,734 individual CLL patients received 48,870 treatment episodes using a total 1,324,926 grams of IVIg therapy. Six IVIg products were available, with domestically manufactured Intragam P accounting for 89.7% of supply. The average age for first dose was 74 years. Males received 60.6% of the total treatment episodes representing 20% more than females. The average pre-treatment IgG level was 4.03g/L +/- 2.03g/L (range 0.30-10.50g/L). A sustained average annual increased IVIg utilisation of 5.5% was observed. There was significant regional variation consistent with differences in prescriber preferences across states and territories. Conclusion This study provides a globally unique insight into IgRT supply and demand in CLL patients by analysis of total national use in Australia over a six year period.

High Dose Steroids as First-Line Treatment Increased the Risk of In-Hospital Infections in Patients With Anti-NMDAR Encephalitis

ObjectiveTo address the effects of high dose steroids on in-hospital infection and neurologic outcome in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients.MethodsWe retrospectively reviewed the clinical data of anti-NMDAR encephalitis patients in West China Hospital, the Third Hospital of Mianyang and Mianyang Central Hospital between October 2011 and August 2020. The development of infections, inflammatory factors, neurologic outcome at discharge and risk factors for in-hospital infection were assessed in patients with and without high dose steroid therapy before and after immunotherapy. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression models were established to assess risk factors for in-hospital infection.ResultsA total of 278 patients with anti-NMDAR encephalitis were included in the study. Thirty-four patients received high dose methylprednisolone (IVMP) therapy only, 84 patients received intravenous immunoglobulin (IVIG) therapy, and 160 patients received IVIG and IVMP therapy. Compared with the IVIG group, IVIG + IVMP group had a higher infection rate (64.38% vs 39.29%, P < 0.001), a higher incidence of noninfectious complications (76.25% vs 61.90%, P = 0.018) and a higher modified Rankin Scale (mRS) score at discharge from the hospital (3 vs 2, P < 0.001). Inflammatory indicators, including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), were higher (9.93 vs 5.65, 6.94 vs 3.47 and 1.47 vs 0.70, respectively, P < 0.001) in the IVIG + IVMP group than in the IVIG group. Moreover, lymphocyte-to-monocyte ratio (LMR) was lower (2.20 vs 2.54, P = 0.047) in the IVIG + IVMP group. The LASSO model showed that mRS score on admission, seizure, body temperature, uric acid (URIC), cerebrospinal fluid immunoglobulin G (CSF IgG), NLR and LMR were risk factors for in-hospital infection. The prediction model exhibited an area under the curve (AUC) of 0.885.ConclusionsHigh dose steroids therapy was significantly associated with higher in-hospital infectious complication rates and a poor short-term prognosis in relatively severe anti-NMDAR encephalitis patients. The established prediction model might be helpful to reduce the risk of in-hospital infection.

Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy

In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the “common cold”-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients’ sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a “forever necessary therapy” for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.

Case Report: Isolated, unilateral oculomotor palsy with anti-GQ1b antibody following COVID-19 vaccination

Neurological complications following vaccinations are extremely rare, but cannot be eliminated. Here, we report the first case of unilateral oculomotor nerve palsy (ONP) with anti-GQ1b antibody after receiving the Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccine. A 65-year-old man developed diplopia and ptosis in the right eye 17 days after vaccination, without preceding infection. Neurological examination revealed mild blepharoptosis, limitation of adduction, and vertical gaze on the right side. Increased levels of anti-GQ1b ganglioside antibody in the serum and albuminocytologic dissociation in the cerebrospinal fluid were detected. Cranial magnetic resonance imaging showed swelling and enhancement of the right oculomotor nerve. The patient was diagnosed with right ONP accompanied with anti-GQ1b antibody, and intravenous immunoglobulin (IVIG) therapy for 5 days was administered. The limitation of adduction and vertical gaze improved, and ptosis markedly resolved after IVIG treatment. Given the temporal sequence of disease progression, laboratory findings, and a favorable response to IVIG, a causal relationship cannot be ruled out between the occurrence of ONP and COVID-19 immunization. Since immunomodulatory treatments significantly hasten the recovery and minimize the residual symptoms in anti-GQ1b antibody syndrome, clinicians should be aware of this clinical condition following COVID-19 vaccination.

Clinical outcomes of intravenous immunoglobulin therapy in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study

Background Intravenous 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. Methods We 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. Results Among 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. Conclusion IVIG 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.

Neonatal hemochromatosis attributed to gestational alloimmune liver disease treated with intravenous immunoglobulin and exchange transfusion therapy: an evidence-based case report

Neonatal hemochromatosis (NH) is a rare fatal liver disease accompanied by hepatic and extrahepatic iron overload.1-3 Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder and leading cause of NH.2,4,5 This condition allows an interplay between the maternal adaptive immune system and the fetus, resulting in an allograft to the mother. The mother becomes sensitized to an alloantigen expressed by the fetus and forms specific reactive antibodies. Immunoglobulin G (IgG) is transported through the placenta and attacks the fetal hepatocytes, resulting in severe loss of hepatocytes and fetal iron overload.3,6 Liver transplantation has been the only definitive treatment for NH for many years, with a survival rate of ±35%. Conventional therapy containing antioxidants and chelation agents reportedly have very poor success, with survival rate of only 10-20%. A new treatment paradigm involving intravenous immunoglobulin (IVIG) and exchange transfusion (ET) therapy has shown significant success in survival rate in NH, decreasing the need for liver transplantation.3,7,8 Here we present a case of NH caused by GALD and treated successfully with a combination of IVIG therapy and ET. We also aimed to evaluate the efficacy of IVIG and ET therapy for NH.

Association Between IL-23 and Coronary Arterial Lesions in Children with Kawasaki Disease

The pathogenesis of coronary artery lesions (CALs) in KD patients has been thought of as an unknown stimulus that triggers an inflammatory cascade with activation of the immune system. However, interleukin-23 (IL-23) is supposed as a key cytokine in inflammatory and autoimmunity diseases. The role of IL-23 in the pathogenesis of CALs has not been fully elucidated. This study explored the relationship between the serum IL-23 levels and CALs in patients with KD. We collected blood specimens from 90 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-23, IL-6, IL-17A, IL-10, MCP-1 and VEGF were measured in 190 cases, including 4 groups: KD with CALs (n = 46), KD without CALs (n = 44), febrile control group, (FC, n = 40) and normal control group, (NC, n = 60). Clinical parameters were tested in all subjects. IL-23 was significantly elevated in the KD group compared with the febrile and normal control groups, especially increased in the KD patients with CALs. Serum levels of IL-23 in KD patients were positively associated with WBC, CRP, IL-6, IL-17A, IL-10, MCP-1, and VEGF in children with KD. In conclusion, IL-23 may be involved in the pro-inflammatory process and the pathogenesis of CALs in KD patients.