High-dose Intravenous Immunoglobulin Treatment Research Articles

EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN ALONE ON CORONARY ARTERY LESION REDUCTION IN KAWASAKI DISEASE.

Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. This clinical trial was structured as a prospective, evaluator-blinded, multi-center randomized controlled trial with two parallel arms, aiming to assess the effectiveness of IVIG as a standalone primary therapy of KD in comparison to the combination of IVIG with high-dose aspirin therapy. KD patients were enrolled between September, 2016 and August, 2019. A final cohort of 134 patients were randomly assigned to the standard and test groups with 69 and 65 patients, respectively. The Standard group received IVIG (2 g/kg) along with aspirin (80-100 mg/kg/day) until fever subsided for 48 hours. The test group received IVIG (2 g/kg) alone. Following the initial treatment, both groups received a daily aspirin dose (3-5 mg/kg) for six weeks. The primary outcome measure was the occurrence of coronary artery lesions (CAL) at the 6-8 weeks mark. The secondary outcome is IVIG resistance. The overall rate of CAL in test group decreased from 10.8% at diagnosis to 1.5% and 3.1% at 6 weeks and 6 months, respectively. The CAL rate of standard group declined from 13.0% to 2.9% and 1.4%, with no statistically significant difference (P>0.1) in the frequency of CAL between the two groups. Furthermore, no statistically significant differences were found for treatment (P>0.1) and prevention (P>0.1) effect between the two groups. This marks the first prospective multi-center randomized controlled trial comparing the standard treatment of KD using IVIG plus high-dose aspirin against IVIG alone. Our analysis indicates that addition of high-dose aspirin during initial IVIG treatment is neither statistically significant nor clinically meaningful for CAL reduction. URL: http://www.clinicaltrials.gov ; identifier: NCT02951234. This study represents the first multi-center randomized controlled trial investigating the efficacy of high-dose aspirin or intravenous immunoglobulin (IVIG) during the acute stage of KD. This study assessed the impact of discontinuing high-dose aspirin (80-100 mg/kg/day) on the occurrence of CAL during the acute phase treatment of Kawasaki Disease.No significant differences were observed between high-dose aspirin plus IVIG treatment and IVIG alone treatment in terms of the frequency of abnormal coronary artery abnormalities. Additionally, our analysis revealed no statistically significant differences in either the treatment effect (the number of cases successfully treated) or prevention effect (the prevention of new cases) between these two treatments. Comparison analysis indicated the non-inferiority between two groups with or without high-dose aspirin.Administering the standard 2 g/kg/day IVIG without high-dose aspirin (80-100 mg/kg/day) during the acute phase therapy for KD does not increase the risk of coronary artery lesions, which are a primary cause of morbidity and mortality in KD patients.Addition of high-dose aspirin during initial IVIG treatment is not statistically significant or clinically meaningful.

Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation: a case report and literature review

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain-Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

면역 글로불린 저항성을 보인 5명의 가와사키병 환아에서의 혈장 교환술을 통한 치료

The efficacy of high-dose intravenous immunoglobulin (IVIG) treatment for acute-stage Kawasaki disease patients has become widely recognized. However, in the case of refractory Kawasaki disease, alternative treatment should be considered to prevent coronary artery abnormality (CAA). Here, we present several cases of Kawasaki disease in children treated with plasma exchange (PE). We retrospectively reviewed the medical records of 5 subjects who had been unresponsive to IVIG treatments and treated with PE consecutively. The fever subsided and the other clinical manifestations were improved after PE in all cases. In two cases, giant coronary artery aneurysms were detected on echocardiographic follow-up study. PE should be a method with promising efficacy and might be considered in refractory Kawasaki disease patients for whom other treatment options have failed.

Incidence of Myocarditis Associated with Diphtheria, Tetanus, and Pertussis Vaccine: A Rare Case Series

AbstractMyocarditis induced by diphtheria–tetanus–pertussis (DTP) vaccination is extremely rare, accounting for only two cases thus far. Hence, to supplement knowledge regarding its pathogenesis and treatment, we reported two cases of myocarditis associated with DTP vaccination in adults.Two patients (a 40-year-old female and a 43-year-old male) presented with mild symptoms and were hemodynamically stable. In both patients, the DTP vaccination was given 4 and 6 days before admission. Both patients had prolonged corrected QT interval (QTc), poor left ventricular function, and high troponin levels at admission. However, numerous ST segment depression was only noted in the first case. Bacteriology and virology study results were negative for any pathogen. No atherosclerotic lesions were observed by coronary angiography. Cardiac magnetic resonance imaging was only performed in the second case, which confirmed the diagnosis of myocarditis. Initial therapy was administered with a beta-blocker, angiotensin-converting enzyme inhibitor, and intravenous methylprednisolone. Nonetheless, in the first case, rapid clinical deterioration and sudden cardiac death occur within 3 days of hospitalization. Learn from the first case, a high-dose intravenous immunoglobulin (IVIG) treatment was initiated in the second case, which resulted in an improvement in left ventricular function and clinical symptoms, as well as a significant reduction in QTc interval and troponin levels.Rapid diagnostic testing and early recognition of the fulminant course is mandatory, allowing clinicians to aggressively treat the patient with high-dose intravenous immune globulin, thus obtaining a better outcome.

Case Report: Treatment for steroid-refractory immune-related myocarditis with tofacitinib

IntroductionImmune therapy has ushered in a new era of tumor treatment, at the expense of immune-related adverse events, including rare but fatal adverse cardiovascular events, such as myocarditis. Steroids remain the cornerstone of therapy for immune-related myocarditis, with no clear consensus on additional immunosuppressive treatment for steroid-refractory cases yet.Case reportHere, we report a patient with stage IV nasopharyngeal carcinoma who developed immune-related myocarditis in the fourth course of therapy with immune checkpoint inhibitors. The patient presented with precordial discomfort with elevation of cardiac enzymes and interleukin-6, atypical electrocardiographic abnormalities, and reduced left ventricular ejection fraction. Coronary computed tomography angiography excluded the possibility of acute coronary syndrome. The therapy with tofacitinib targeting the Janus kinase-signal transducer and activator of transcription signal pathway was successfully conducted, since there was no significant improvement in troponin under high-dose steroid and intravenous immunoglobulin treatment. The patient recovered without major adverse cardiac events during hospitalization.DiscussionThe safety and efficacy of tofacitinib in a patient with steroid-refractory immune-related myocarditis were investigated, hoping to provide a basis for prospective therapeutic strategies. Tofacitinib led to remarkable remissions in primary autoimmune disease by blocking the inflammatory cascade, indicating its potential therapeutic use in immune-related adverse events.

Central nervous system neurotoxicity associated with nelarabine in T-cell acute lymphoblastic leukemia.

Nelarabine, a prodrug of arabinosylguanine has lineage-specific toxicity for T lymphoblasts and is used to treat refractory or relapsed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma patients. The most commonly observed adverse effects associated with nelarabine are mainly hematological, i.e. neutropenia, anemia, and thrombocytopenia. Additionally, neurological, and gastrointestinal toxicities have been reported. Central nervous system neurotoxicity associated with nelarabine is very rare. A 37-year-old man patient diagnosed with T-cell acute lymphoblastic leukemia had experienced generalized tonic-clonic seizure which lasted for a few seconds and upper extremity weakness after three weeks of the nelarabine infusion. Computed tomography and magnetic resonance imaging have shown periventricular and nucleus caudatus abnormalities. Radiological findings suggested toxic leukoencephalopathy and acute infarct of right nucleus caudatus. After high-dose steroids, intravenous immunoglobulin, and support treatment, his neurologic symptoms disappeared except for mild peroral numbness. However, radiological sequelae persisted despite clinical improvement. Physicians involved in the care of these patients who use nelarabine should be aware of the fact that cerebral toxicity of the nelarabine may occur especially in the presence of predisposing factors. It is crucial to monitor closely those patients receiving nelarabine and also those who have additional predisposing factors for neurotoxicity.

Low IgG trough and lymphocyte subset counts are associated with hospitalization for COVID-19 in patients with primary antibody deficiency

Low IgG trough and lymphocyte subset counts are associated with hospitalization for COVID-19 in patients with primary antibody deficiency

Desensitization Regimen Consisting of High-Dose Intravenous Immunoglobulin, Plasmapheresis, and Rituximab (an Anti-CD20 Antibody), Without Eculizumab and/or Bortezomib, in 41 Highly Sensitized Kidney Transplant Recipients.

Antibody-mediated rejection in patients with positive crossmatches can be severe and result in sudden onset of oliguria, leading to graft loss. In an attempt to prevent posttransplant oliguria, we adopted a preoperative desensitization protocol involving the use of high-dose intravenous immunoglobulin/plasmapheresis and the anti-CD20 antibody, rituximab, in 41 transplant recipients with positive crossmatch test results. We retrospectively examined the clinical courses of the 41 kidney transplant recipients, paying special attention to renal graft function, urine volume, and changes in the titers of donor-specific antibodies. Four grafts were lost during an average of 4.5-year follow-up. Average graft function was excellent, with a serum creatinine level of 1.3 ± 0.4 mg/dL. Sufficient urine output, with no oliguria or anuria, was achieved postoperatively in 40 of the 41 patients. However, among the 34 patients who underwent graft biopsies, the biopsies revealed acute antibody-mediated rejection in 21 patients (62%), and chronic antibodymediated rejection in 10 patients (30%). The high-dose intravenous immunoglobulin treatment included in our desensitization protocol was shown to be safe and effective for achieving successful transplant outcomes and allowed the avoidance of more aggressive B-cell-targeted treatments, such as C5 inhibitors and/or proteosome inhibitors, for preventing posttransplant oliguria and anuria.

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation.

Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for immune dysregulation diseases. However, the mechanisms by which it reduces systemic inflammation are not well understood. NK cell cytotoxicity is decreased by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte function, especially in NK cells, is important for resolution of inflammation. Our aim was to identify IVIG-induced changes in a cohort of patients with Kawasaki disease (KD) and those that occur broadly in pediatric patients with various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG infusion Treg cell frequency and the proportion of activated CD25+ immunoregulatory CD56bright NK cells was increased, and multiple lymphocyte subsets showed increased expression of the lymphoid tissue homing receptor CD62L. Importantly, IVIG treatment decreased the frequency of cells expressing the degranulation marker CD107a among cytotoxic CD56dim NK cells, which was reflected in a significant reduction in target cell killing and in decreased production of multiple pro-inflammatory mediators. Interestingly, the activating receptor CD336 was expressed on a higher proportion of CD56bright NK cells after IVIG in both KD and autoimmune/inflammatory patients while other NK receptors were increased differentially in each cohort. In autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a higher percentage of CD56dim NK cells, and in contrast to KD patients, CD107a+ cells were increased in this subset. Furthermore, when PBMCs were stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the CD4+ T cells of KD patients expressed CD25 after IVIG therapy but fewer cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG treatment in patients with immune dysregulation has multiple effects, especially on NK cell subsets and CD4+ T cells, which are compatible with promoting resolution of inflammation. These novel findings provide insight into the immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.

Roles of immune responses in the pathogenesis of immunorelated pancytopenia.

Some patients with pancytopenia do not conform to any diagnostic criteria of known haematological or non-haematological diseases; however, they respond well to corticosteroid, high-dose intravenous immunoglobulin and rituximab treatment. This abnormality is termed immunorelated pancytopenia (IRP). Later studies indicated that IRP might be a kind of autoimmune disease in which T helper (Th) type 2 cell function is enhanced, resulting in the hyperfunction of B lymphocytes, which then produce excess autoantibodies that attack the bone marrow (BM) and cause cytopenia. Hypofunction of regulatory T (Treg) cells and enhanced Th17 cell function, an elevated percentage of plasmacytoid dendritic cells (pDCs) and a decreased percentage of natural killer (NK) cells help to promote the process. Moreover, increased expression of a synergistic stimulator of B lymphocytes, CD70 and the reactive overexpression of the BCR inhibitory coreceptor CD22 also support this claim. Candidate autoantigens targeted by autoantibodies on haematopoietic cell membranes have also been reported in IRP. This review is focused on studies that demonstrate the role of immune responses in the pathogenesis of IRP. Current diagnostic criteria and treatments for IRP are also referenced to provide a thorough understanding. Distinguishing IRP from idiopathic cytopenias of undetermined significance (ICUS) and other haematological disorders, for example myelodysplastic syndrome (MDS), aplastic anaemia (AA), paroxysmal nocturnal hemoglobinuria (PNH) and Evans syndrome, may help patients with pancytopenia benefit from proper treatment. Further studies are required to achieve new insight into the pathophysiology of IRP with regard to the immune system, which will be instrumental for the development of novel therapies for inhibiting disease initiation and/or progression.

Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia.

This study aimed to investigate the relationship between CD4+ regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy. We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100×109 /L at 12 months after IVIG treatment. Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho=0.72) and negatively correlated with both ILC1 (rho=-0.49) and ILC3 (rho=-0.60) (P<0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n=8) versus responders (n=22; P<0.05). We found that Tregs suppressed proliferation of ILCs and CD4+ T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4+ CD45RO+ T cells in vitro following IVIG therapy. Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.

High-Dose Intravenous Immunoglobulin in Skin Autoimmune Disease.

The immunomodulatory potential and low incidence of severe side effects of high-dose intravenous immunoglobulin (IVIg) treatment led to its successful application in a variety of dermatological autoimmune diseases over the last two decades. IVIg is usually administered at a dose of 2 g per kg body weight distributed over 2–5 days every 4 weeks. They are most commonly used as a second- or third-line treatment in dermatological autoimmune disease (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, dermatomyositis, systemic vasculitis, and systemic lupus erythematosus). However, first-line treatment may be warranted in special circumstances like concomitant malignancy, a foudroyant clinical course, and contraindications against alternative treatments. Furthermore, IVIg can be considered first line in scleromyxedema. Production of IVIg for medical use is strictly regulated to ensure a low risk of pathogen transmission and comparable quality of individual batches. More common side effects include nausea, headache, fatigue, and febrile infusion reactions. Serious side effects are rare and include thrombosis and embolism, pulmonary edema, renal failure, aseptic meningitis, and severe anaphylactic reactions. Regarding the mechanism of action, one can discriminate between functions of the Fcγ region and the F(ab)2 region and their effects on a cellular level. These functions are not mutually exclusive, and more than one pathway may contribute to the beneficial effects. Here, we present a historical background, details on manufacturing, hypotheses on the mechanisms of action, information on the clinical application in the abovementioned conditions, and a brief outlook on future directions of IVIg treatment in dermatology.

Augmented ILT3/LILRB4 Expression of Peripheral Blood Antibody Secreting Cells in the Acute Phase of Kawasaki Disease.

Kawasaki disease (KD) is an acute, systemic vasculitis syndrome that occurs in children. The clinical symptoms and epidemiologic features of KD strongly suggest that KD is triggered by unidentified infectious agents in genetically predisposed patients. In addition, a number of studies have described the role of B cells in the development of KD. To obtain a mechanistic insight into the humoral immune response of B-lineage cells in KD patients, we examined peripheral blood antibody secreting cells (ASCs) and inhibitory immunoreceptors, immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LILR), on each B cell subpopulation. Eighteen Japanese KD patients and thirteen healthy control subjects were recruited for this study. Their peripheral blood mononuclear cells were examined by flow cytometry for the number of CD19 B cells, the size of each B cell subset and the expression of the inhibitory isoforms of ILT/LILR on the B cell subset. The frequency of CD19CD27 ASCs was significantly increased in the acute phase of KD and reduced after high-dose intravenous immunoglobulin (IVIG) treatment. Interestingly, while ILT2/LILRB1 expression was ubiquitously observed on every B cell/ASCs subset and the level was not significantly different after IVIG, ILT3/LILRB4 (B4) was uniquely expressed on only ASCs, and its expression was significantly decreased after IVIG. In the acute phase of KD, the frequency of ASCs is high with augmented B4 expression, whereas it is lower with decreased B4 expression after IVIG. Further studies of B4 expression on ASCs in autoimmune and infectious diseases will be needed to confirm the significance of our findings.

The Japanese experience and pharmacokinetics of antenatal maternal high-dose immunoglobulin treatment as a prophylaxis for neonatal hemochromatosis in siblings

Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70–90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited.Objective: We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment.Methods: Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model.Results: Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000–3000 and 4000–5000 mg/dl, respectively.Conclusion: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.

High-Dose Intravenous Immunoglobulin Treatment of Polyomavirus Nephropathy Developing After T Cell–Mediated Rejection Treatment: A Case Report

BackgroundReactivation of BK polyomavirus causes destructive virus allograft nephropathy; however, treatment options are limited. Herein, we report a case in which a patient with T cell–mediated rejection was treated with steroid therapy. The patient subsequently developed BK viremia and was successfully treated by using intravenous immunoglobulin (IVIG) after failing to respond to conventional treatment. Case PresentationA 54-year-old man had been undergoing peritoneal dialysis for 3 years before kidney transplantation. He had an elevated serum creatinine level (2.26 mg/dL; normal range, 1.2–1.4 mg/dL) and reduced urine output 2 months after transplantation. Suspecting T cell–mediated rejection, steroid pulse therapy (methylprednisolone 250 mg twice daily) was performed for 3 days. Despite treatment, there was a recurrence of increased serum creatinine, and real-time quantitative polymerase chain reaction (serum samples) indicated BK viremia (>5.5 × 105 copies/mL). Results of a kidney biopsy revealed polyomavirus nephropathy (BK virus positive and C4d negative). Thus, the patient's tacrolimus dosage was reduced (from 2.75 mg twice daily to 2 mg once daily), he discontinued mycophenolate mofetil, and he was administered ciprofloxacin and leflunomide. However, the BK viremia showed no improvement, even after 3 months of treatment. Thus, he was administered high-dose IVIG (1 g/kg, 5 times over 5 weeks). The viremia load (blood specimen) decreased to 5197 copies/mL, and the patient's graft function stabilized. His serum creatinine decreased to 2.68 mg/dL. The patient is currently being followed up. ConclusionsOptimal BK treatment methods have not been established, and IVIG treatment remains controversial. However, the present case provides an example of successful treatment using high-dose IVIG.

Clinical analysis of Kawasaki disease associated with macrophage activation syndrome and a probe into its diagnostic criteria

Objective To analyze the clinical and laboratory characteristics, treatment, and outcomes of Kawasaki disease (KD) patients associated with macrophage activation syndrome (MAS) (KD-MAS) and to compare three diagnostic standards. Methods Twelve cases of KD-MAS were reviewed retrospectively, who had been treated and therapied at the Children′s Hospital of Chongqing Medical University from September 2007 to September 2017.The clinical data were analyzed.And, the efficacy of different MAS diagnostic criteria for KD-MAS was evaluated. Results The subjects included 8 males and 4 females, with a median age of 25 months.The capital trigger of MAS was infection(8 cases, 66.7%). Unabating high fever had been the initial manifestation for 12 patients(100%), other common clinical features including hepatomegaly(11 cases, 91.6%), splenomegaly(8 cases, 66.7%)and lymphadenectasis(7 cases, 58.3%). Besides, 8 patients (66.7%) had different degrees of central nervous system symptoms.Laboratory examination showed a decrease in hemoglobin (11 cases, 91.6%), in thrombocytopenia (8 cases, 66.7%), and white blood cells (4 cases, 33.3%); while there was an increase were found in serum transaminase (11 cases, 91.6%), triglyceride (72.7%, 8/11 cases) and serum ferritin (100%, 9/9 cases). Eleven patients (91.6%) had decreased erythrocyte sedimentation rates (ESR). Bone marrow cytology was performed in 10 cases, and 8 cases of them showed hemophagocytic phenomenon.All the patients were diagnosed by SoJIA-MAS(2005)criteria.All patients were treated with high-dose intravenous immunoglobulin (IVIG) treatment, among whom 3 cases were combined with methylprednisolone treatment, and 2 cases received with more than 2 kinds of immunosuppressive drugs (Dexamethasone and Ciclosporin or Etoposide). Among the 12 patients, 2 patients lost to follow-up, 4 cases(33.3%) died due to hepatic encephalopathy, including 2 cases who withdrawn treatment the remaining 6 cases(50.0%)improved. Conclusions Prolonged high fever is the first manifestation of MAS in KD.Hemogram and ESR will decrease, elevated serum transaminase and ferritin may increase, which indicates MAS occurrence.If a high dose of IVIG therapy does not work, the combination of glucocorticoid and immunosuppressive for therapy may improve the remission rate.Severe central nervous system involvement may indicate a terrible prognosis.SoJIA-MAS (2005) can diagnose earliler by using preliminary diagnostic guidelines for macrophage activation system complicating systemic juvenile idiopathic arthritis. Key words: Kawasaki disease; Macrophage activation syndrome; Intravenous immunoglobulin; Glucocorticoid

A novel kindred with inherited STAT2 deficiency and severe viral illness

A novel kindred with inherited STAT2 deficiency and severe viral illness

Emerging pharmacologic targets and treatments for myocarditis.

Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alteration of the immune response and antiviral treatments; however, success has been limited. Since the myocarditis treatment trials in the 1990s there has been an improved understanding of disease progression and new facets of the immune response have been discovered. This new information provides fresh opportunities to develop therapeutics to treat myocarditis. This review analyzes previous pharmacologic approaches including immunosuppression, high dose intravenous immunoglobulin treatment, immunoadsorption and antiviral treatments, and looks forward toward recently identified immune factors that can be exploited as targets for new treatments. Such strategies include bolstering beneficial regulatory T cells or mitigating the detrimental Th17 T cells which can drive autoimmunity in the heart. The surging interest of the application of humanized monoclonal antibodies makes targeting deleterious arms of the immune response like Th17 cells a tangible goal in the near future. Promising constituents of herbal remedies have also been identified that may hold potential as new pharmacological treatments for myocarditis, however, significant work remains to elucidate the pharmacokinetics and side-effects of these compounds. Finally, advances in our understanding of the function of Matrix Metalloproteinases yield another target for altering disease progression given their role in the development of fibrosis during Dilated Cardiomyopathy. In bringing to light the various new targets and treatments available since the last myocarditis treatment trials, the aim of this review is to explore the new treatments that are possible in new myocarditis treatment trials.

Abstract 96: Changes In HDL Cholesterol During The Acute Phase of Kawasaki Disease

To determine the correlations between changes in high-density lipoprotein cholesterol (HDL-C) and other blood variables during the acute phase of Kawasaki disease (KD), we investigated changes in the plasma level of HDL-C, serum apolipoproteins and number of peripheral blood monocytes. 26 Japanese patients with KD were subjects of this study. Plasma HDL-C decreased during the 1st week of illness, and increased during the 2nd week. The mean levels of minimum HDL-C in KD patients treated with total intravenous immunoglobulin (IVIG) dose ≧ 4g/kg, was significantly lower than those treated with total IVIG dose &lt; 4g/kg (p=0.0005). There was a strong direct correlation between minimum HDL-C in KD patients and HDL-C on 5th day of KD onset (r=0.71, p &lt; 0.0001). Assessing the performance of plasma HDL-C on 5th day of KD onset in predicting the necessity for high-dose IVIG treatment to KD, ROCs were plotted and the AUC was 0.82. A cutoff value of 16mg/dl had a specificity of 0.82 and sensitivity of 0.80 for predicting those. The apo A-I and A-II levels were correlated with plasma HDL-C, respectively. And the peripheral blood monocytes counts which correlated with serum levels of macrophage-colony stimulating factor, were not correlated with plasma HDL-C. Plasma HDL-C levels during the 1st week of illness might serve as a predictor for non-responder to low-dose IVIG treatment in patients with acute KD.

Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency

Long-term remission after allogeneic hematopoietic stem cell transplantation in LPS-responsive beige-like anchor (LRBA) deficiency