Diversity of IgG autoantibodies of 4 Chinese intravenous immunoglobulins / 中国输血杂志

【Objective】 To develop methods to display the IgG autoantibody repertoire of intravenous immunoglobulin (IVIG) products, analyze the different types of antibodies and study the diversity of IgG autoantibody in 4 IVIG preparations from different Chinese manufacturers. 【Methods】 Two-dimensional gel electrophoresis and immunoblotting with human umbilical vein endothelial cell (HUVEC) proteins were used to demonstrate the IgG autoantibody repertoire and the human protein microarray with bioinformatics analysis was employed to profile the immune reactive autoantigens of the 4 IVIG preparations. 【Results】 The methods to showcase the autoantibody repertoire and study the antibody diversity of IVIG were successfully established. High-quality repertoires of IVIG autoantibodies and biological information about self-proteins that can be recognized were obtained. There was a significant difference in the recognition of the quantity and variety of the self-antigens by different IVIG products. The number of antibodies against HUVEC proteins in four products ranged from 241-386. The number of proteins recognized on the human protein chip ranged from 292-435, with 172 human self-proteins recognized by all four products. 【Conclusion】 Demonstration of antibody repertoire and protein chip technology can be used to analyze IVIG products′ IgG autoantibody repertoire. All four preparations tested in this study exhibited a broad spectrum of antibodies against HUVEC proteins and human proteome microarray, each product had its unique antibody repertoire characteristics.

Technical specification for clinical diagnosis and treatment of human parvovirus B19 infection in kidney transplant recipients (2022 edition) / 器官移植

Long-term use of immunosuppressant in kidney transplant recipients leads to poor immune function and infection with various pathogens. In recent years, along with the advancement of detection technique of human parvovirus B19 (HPV-B19) infection and the increasing quantity of kidney transplantation, the infection rate of HPV-B19 after kidney transplantation has been elevated year by year, becoming one of the major causes of pure red cell aplasia (PRCA), affecting the recovery of renal allograft function, and even leading to the injury or poor prognosis of renal allograft. To further standardize the diagnosis and treatment of HPV-B19 infection in kidney transplant recipients, Branch of Organ Transplantation of Chinese Medical Association and National Kidney Transplantation Quality Control Center jointly organized experts to formulate the clinical diagnosis and treatment specification for HPV-B19 infection after kidney transplantation from the perspectives of etiology, epidemiological characteristics, clinical manifestations, diagnosis, prevention, treatment, existing problems and prospects of HPV-B19, aiming to provide guidance for standardized prevention and treatment of HPV-B19 infection post-kidney transplantation in China.

Clinical outcome of Gullian-Barre Syndrome in a tertiary care teaching hospital A prospective observational study

Background: Gullian-Barre Syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy (AIDP) with autoimmune background. The clinical management of GBS is by nerve conduction velocity (NCV) and supportive care, intravenous immunoglobulin’s (IVIG) and Plasmapheresis. We have studied the clinical outcome of Gullian-Barre Syndrome patients visiting to the tertiary care hospital in Andhra Pradesh. Material and methods: A cross sectional study was conducted in a tertiary care teaching hospital at Andhra Pradesh in 50 patients over the period of 2 years. Neurological examination like higher mental functions, cranial nerves, motor system, sensory system and autonomic system was done for all patients. Descriptive analysis of clinical presentation, type of GBS, occurrence of complications and final outcome was also done. Results: A total of 50 participants were included in the study. Majority (52%) of the study participants were aged below 40 years. Diabetes mellitus (DM) and hypertension (HTN) were the Vasa VK, Chowdary DB, Kalyani OM. Clinical outcome of Gullian-Barre Syndrome in a tertiary care teaching hospital – A prospective observational study. IAIM, 2016; 3(1): 105-109. Page 106 most common co-existing illnesses reported in 8% and 6% of study population respectively. Conclusion: The majority of the Guillain-Barre Syndrome patients recovered smoothly without going for complications. Prognostic outcome was poor in our study with increasing age and co-existing illness like diabetes mellitus or ischemic heart disease.

A 4-year retrospective study of Stevens-Johnson syndrome and toxic epidermal necrolysis

Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare bullous mucocutaneous disease usually caused by drugs. We aim to determine the demographics, causes and outcomes of patients admitted with SJS, TEN and SJS-TEN overlap in Sarawak General Hospital. Materials and Methods A retrospective review of cases admitted to Sarawak General Hospital with SJS, TEN and SJS-TEN overlap from January 2004 to December 2007 was undertaken. Data regarding the demographic, causes and outcomes were collected from the case folders and subjected to descriptive statistical analysis using Microsoft Excel. Results Twenty four cases were admitted with 54.2% having SJS, 25% having SJS-TEN Overlap and 20.8% having TEN. With the mean ages of more than 40 years, patients with SJS and SJS-TEN overlap were older than patients with TEN, with a mean age of only 25.4 years. Seventy nine percent of cases were drugs induced. Anticonvulsants were the main culprit constituting 29.2% followed by allopurinol with 20.8%. Cases with SJS had the longest incubation period with mean of 21.6 days whereas cases with TEN had the longest mean hospital stay with 12.4 days. A 12.5% mortality rate was recorded with 2 deaths in the SJS-TEN overlap group and one death in the TEN group. All cases who were given intravenous immunoglobulin (IVIg) survived. Conclusion SSJS, SJS-TEN Overlap and TEN were mainly drug induced and have high mortality. IVIg treatment seems promising. Early recognition and optimal care in institution with dermatology service is essential in reducing morbidities and mortalities.

Pure Red Cell Aplasia (PRCA) due to Parvovirus B19 Infection after Kidney Transplantation / 대한이식학회지

The patient was a 39-year-old male with anemia persistent after a living-related renal transplantation. He was diagnosed to have pure red cell aplasia (PRCA) due to parvovirus B19 infection on the 6th week after the renal transplantation. Serum Parvovirus B19 DNA polymerase chain reaction (PCR) and anti-Parvovirus B19 IgM were positive and bone marrow aspiration biopsy showed giant pronormoblasts including prominent intranuclear inclusions. He has been receiving immunosuppressive therapy including oral cyclosporine A, prednisolone, mycophenolate mofetil (MMF). After diagnosis of pure red cell aplasia, we reduced the dose of cyclosporine A and maintained prednisolone, mycophenolate mofetil. We used intravenous immunoglobin(IVIG) 0.4 g/kg/ day for 5 days. Patient's serum reticulocyte count increased a week after the treatment from 0.1% to 3.8%, and patient's serum hemoglobin level normalized on the 4th week of the treatment. Presently, 20 weeks following the initiation of IVIG, his hemoglobin remains normal without recurrent symptom. We are planning to follow up the serum anti-parvovirus B19 IgM/IgG and parvovirus B19 DNA PCR examination.

Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone / 소아과

PURPOSE: Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin (IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor (VEGF)- induced tube formation of endothelial cells in vitro on Matrigel assay. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents: VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. RESULTS: IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. CONCLUSION: We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

Effect of Intravenous Immunoglobulin(IVIG) on Renal Function in Very Low Birth Weight Infants

PURPOSE: This study was conducted to evaluate the effect of IVIG infusion on renal function in VLBW infants. IVIG has been proved quite safe in neonates given prophylactic and therapeutic doses. But nephrotoxicity is not recognized as adverse in IVIG therapy, only several previous adult cases have been noted. METHODS: For a total of ten VLBW infants who had not been received any medication except parenteral nutrition, vitamin and Fe supplements was assigned for study. To observe changes in renal function after preventive dose of IVIG administration(500mg/kg, 1dose) serum BUN and creatinine, 2-microglobulin( 2-MG) and N-acetyl- -D-glucosaminidase(NAG) were obtained prior to study and 1, 3 and 7 days after infusion. RESULTS: 1) There were no elevation of serum BUN and creatinine after IVIG administration, 2) There was transient increase of urine NAG from 1.1+/-0.7 u/mg creatinine before infusion to 2.7+/-5.3 u/mg creatinine on the first day of infusion, which was not statistically significat, decreasing to pretreatment level on the 3rd and 7th days after infusion. 3) There was transient increase of urine 2-MG from 294.6+/-223.8 microgram/mg creatinine before infusion to 680.0+/-108.9 microgram/mg creatinine on the first day and 416.0+/-246.3 microgram/mg creatinine on 3rd day after infusion, which was not statistically significant. CONCLUSIONS: It was found that prophylactic dose of IVIG in VLBW infants does not cause clinically significant impairment of renal function. but mild increment of urine NAG and 2-MG may suggest the possibility of renal tubular damage. Based on these results, further evaluation of the effect of IVIG on renal function in VLBW infant is recommended.

Immunologic Abnormalities in Kawasaki Disease and the Effect of Intravenous Immunoglobulin

PURPOSE: It has been suggested that immunologic abnormalities play a role in the pathogenesis of vascular injury in Kawasaki disease and the immunologic abnormalities could be regulated by high-dose intravenous immunoglobulin(IVIG). We investigated the peripheral blood lymphocyte subsets, the serum levels of interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-alpha) and the effect of high- dose IVIG(400 mg/kg/day for 5 days) on these factors during acute stage of Kawasaki disease. METHODS: Thirty patients, aged 4 months to 5 years, who met the diagnostic criteria for Kawasaki disease were enrolled in this study. Patients were divided into two groups, Kawasaki disease with coronary vascular lesion(KD-CVL) and without coronary vascular lesion (KD-NCVL). Percentages of peripheral blood lymphocyte subsets were measured by flow-cytometry and the serum levels of IL-6 and TNF-alpha were measured by ELISA on 1 day before and 1 day after IVIG administration and compared with normal control group(n=15). RESULTS: The results were as follows 1) Before IVIG administration, the percentages of CD3+ lymphocyte and CD8+ lymphocyte in both KD-CVL and KD-NCVL were significantly lower than those in control group. The percentages of CD19+ lymphocyte and CD4+/CD8+ ratio in both groups were significantly higher than those in control group. There was no significant differences between the percentages of CD4+ lymphocyte in both groups and that in control group. 2) After IVIG administration, the percentages of CD3+ lymphocyte and CD8+ lymphocyte in both KD-CVL and KD-NCVL were significantly increased. The percentages of CD19+ lymphocyte and CD4+/CD8+ ratio in both KD-CVL and KD-NCVL were significantly decreased. The percentages of CD4+ lymphocyte were not changed. 3) Before IVIG administration, the detection rate of serum IL-6 and TNF-alpha in both groups was significantly higher than that in control group. After IVIG administration, the detection rate of serum IL-6 in both groups was still higher than that in control group. In KD-CVL, the detection rate of serum TNF-alpha was still higher than that in control group but there was no significant difference between the detection rate of TNF-alpha in KD-NCVL and that in control group. 4) Before IVIG administration, the serum levels of IL-6 in Kawasaki disease were significantly higher than that in control group but there was no significant difference between those in KD-CVL and KD-NCVL. After IVIG administration, the serum level of IL-6 in KD-CVL was not decreased. In KD-NCVL, it was decreased significantly but it was still higher than that in control group after IVIG administration. Before IVIG administration, the serum levels of TNF-alpha in Kawasaki diseases were significantly higher than that in control group and that in KD-CVL was significantly higher than that in KD-NCVL. After IVIG administration, the serum level of TNF-alpha in KD-CVL was not decreased but in KD-NCVL, it was decreased significantly to the level of control group. CONCLUSIONS: Immunologic abnormalities including decreased percentage of CD3+ lymphocyte, CD8+ lymphocyte, increased percentage of CD19+ lymphocyte and CD4+/ CD8+ ratio and increased levels of IL-6 and TNF-alpha were noted in the acute stage of Kawasaki diseases. But there were no difference of above immunologic abnormalities between KD-CVL and KD-NCVL. After IVIG administration, the abnormal percentages of peripheral blood lymphocyte subsets were changed to normal but in the cases of IL-6 and TNF-alpha, the levels were continuously elevated except TNF-alpha in KD-NCVL. Therefore the immunologic abnormalities including abnormal percentages of peripheral blood lymphocyte subsets and increased production of IL-6 and TNF-alpha might be involved in the pathogenesis of Kawasaki disease. And IVIG has some effects on the change of these kinds of immunologic abnormalities.