Objective: To evaluate the safety and immunogenicity of hepatitis E vaccine(HEV)in Maintenance hemodialysis(MHD)patients. Methods: Based on an open-labeled controlled trial, from May 2016 to March 2018, 35 eligible MHD patients were recruited in the Hemodialysis Center of Zhongshan Hospital Affiliated to Xiamen University as the experimental group, and 70 MHD patients with matched age, gender and underlying diseases as the control group. The experimental group received HEV at 0, 1 and 6 months according to the standard vaccination procedures, while the control group received routine diagnosis and treatment without vaccine and placebo injection to observe the safety and immunogenicity of the vaccine. The safety of vaccine in MHD population was evaluated by the incidence of adverse reactions/events in the experimental and control groups. The immunogenicity of HEV in MHD patients was evaluated by comparing the data from the phase Ⅲ clinical trial. Results: The overall incidence of adverse reactions/events was 17.1% (18/105), and there were no grade 3-4 adverse reactions/events related to vaccination. In the experimental group, the incidence of local adverse reactions/events was 20.0% (7/35), and the incidence of systemic adverse reactions/events was 17.1% (6/35).There was no significant difference in the incidence of systemic adverse reactions/events between the experimental group and the control group (P>0.05). There were 23 patients receiving 3 doses with the standard schedule. The positive rate of HEV-IgG antibody was 100% and the GMC was 14.47(95%CI:13.14-15.80) WU/ml, which showed no significant difference compared with the 46 patients in Phase Ⅲ clinical trial (t=-1.04, P>0.05). Conclusion: Recombinant HEV has good safety and immunogenicity in MHD patients.
Clinical Trials, Phase III as Topic ; Female ; Hepatitis E ; Humans ; Immunogenicity, Vaccine ; Immunoglobulin G ; Male ; Renal Dialysis ; Viral Hepatitis Vaccines/adverse effects*

Objective: To investigate the risk factors and outcomes of cytomegalovirus (CMV) infection post umbilical cord blood stem cell transplantation (UCBT) in children with primary immunodeficiency diseases (PID). Methods: Clinical data of 143 PID children who received UCBT in the Children's Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively. CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT. According to the CMV-DNA test results, children were divided into the CMV-infected group and the CMV-uninfected group. The incidence and risk factors of CMV infection were analyzed. At 1-month post-UCBT, the absolute lymphocyte count, ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not. Mann-Whitney U test and chi-squared test were used for comparision between groups. Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival. Results: Among 143 patients, there were 113 males and 30 females, with a age of 14 (8, 27) months at UCBT. Chronic granulomatosis disease (n=49), very-early-onset inflammatory bowel disease (n=43) and severe combined immunodefiency (n=29) were the three main kinds of PID. The rate of CMV infection was 21.7% (31/143), and the time of infection occurring was 44 (31, 49) days post-UCBT. The incidence of recurrent CMV infection was 4.2% (6/143) and refractory CMV infection was 4.9% (7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group (32.8 (18.3, 63.1)×10⁶ vs. 22.5 (13.2, 31.9)×10⁶ copies/L, Z=-0.95, P=0.340;35.2 (20.2, 54.6)×10⁶ vs. 28.4 (24.1, 53.5)×10⁶copies/L, Z=-0.10, P=0.920), so were those between the refractory CMV infection group and non-refractory CMV infection group (21.8 (13.1, 32.2)×10⁶ vs. 25.9 (14.2, 12.2)×10⁶copies/L, Z=-1.04, P=0.299; 47.7 (27.9, 77.6)×10⁶ vs. 27.7 (19.7,51.8)×10⁶copies/L, Z=-1.49, P =0.137). The CMV-infected group accepted more reduced-intensity conditioning (RIC) regimen than the CMV-uninfected group (45.2% (14/31) vs. 25.0% (28/112), χ²=4.76, P<0.05). The rate of CMV-seropositive recipients and Ⅱ-Ⅳ acute graft versus host diseases (aGVHD) are significantly higher in the CMV-infected group than the CMV-uninfected group (100% (31/31) vs. 78.6% (88/112), 64.5% (20/31) vs. 26.8% (30/112), χ²=7.98,15.20, both P<0.05). The follow-up time was 31.6 (13.2, 45.9) months, CMV infection had no effect on overall survival (OS) rate (χ²=0.02, P=0.843). There was significant difference in the survival rate among three groups of refractory CMV infection, non-refractory CMV infection and the CMV-uninfected (4/7 vs.95.8% (23/24) vs. 86.6% (97/112), χ²=5.91, P=0.037), while there was no significant difference in the survival rate among three groups of recurrent CMV infection, non-recurrent CMV infection and the CMV-uninfected (5/6 vs. 88.0% (22/25) vs. 86.6% (97/112), χ²=0.43, P=0.896). Children who developed CMV infection after 30 days post-UCBT had lower absolute count and rate of CD4⁺ T cells and immunoglobulin G (IgG) level than those in the CMV-uninfected group (124.1 (81.5, 167.6) ×10⁶ vs. 175.5 (108.3, 257.2) ×10⁶/L, 0.240 (0.164, 0.404) vs. 0.376 (0.222, 0.469), 9.3 (6.2, 14.7) vs. 13.6 (10.7, 16.4) g/L, Z=-2.48, -2.12,-2.47, all P<0.05), but have higher rate of CD8⁺T cells than those in CMV-uninfected group (0.418 (0.281, 0.624) vs. 0.249 (0.154, 0.434), Z=-2.56, P=0.010). Conclusions: RIC regimen, grade Ⅱ-Ⅳ aGVHD and CMV-seropositive recipients are the main risk factors associated with CMV infection in PID patients post-UCBT. Survival rate of children with refractory CMV infection after UCBT is reduced. Immune reconstitution in children after UCBT should be regularly monitored, and frequency of CMV-DNA monitoring should be increased for children with delayed immune reconstitution.
Child ; Cord Blood Stem Cell Transplantation/adverse effects* ; Cytomegalovirus ; Cytomegalovirus Infections/etiology* ; DNA ; Female ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Immunoglobulin G ; Infant ; Male ; Primary Immunodeficiency Diseases ; Prognosis ; Retrospective Studies ; Risk Factors

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next-generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.
Animals ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Glycosylation ; Humans ; Immunoglobulin G ; chemistry ; metabolism ; Protein Engineering ; methods ; Receptors, Fc ; chemistry ; metabolism ; Treatment Outcome

BACKGROUND: Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring. METHODS: Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays. RESULTS: We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 μg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 μg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 μg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 μg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively). CONCLUSION The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.
Adult ; Air Pollutants, Occupational ; adverse effects ; immunology ; Environmental Monitoring ; Humans ; Immunoglobulin G ; blood ; immunology ; Japan ; Male ; Manufacturing and Industrial Facilities ; statistics & numerical data ; Middle Aged ; Occupational Diseases ; blood ; chemically induced ; Occupational Exposure ; adverse effects ; statistics & numerical data ; Phthalic Anhydrides ; immunology ; toxicity ; Respiratory Hypersensitivity ; blood ; chemically induced ; Toluene 2,4-Diisocyanate ; immunology ; toxicity ; Workforce

Patients who transplanted for non-autoimmune indication may developed de novo autoimmune hepatitis after liver transplantation. It happens about 1.7%-6.6% in liver transplanted population. Most patients with de novo AIH had transplanted for HCV infection, biliary atresia and Cholestatic liver disease. The interval between transplantation and de novo AIH onset is from 3 month to 16 years, mostly more than 1 year. The disease can be seen at any age. More female patients are present in children, while there is no significant difference between male and female in adults. Clinical manifestations of de novo AIH are similar to those of AIH, namely characterized by elevated transaminase with or without bilirubin, as well as elevated serum gammaglobulin (IgG) and positive autoantibodies, while the histological features of an infiltrate rich in plasma cells with interface hepatitis and necro-inflammation and fibrosis. Treatment with corticosteroids and Azathioprine brings good outcomes, but it tends to fluctuate.
Adult ; Autoantibodies ; blood ; Bilirubin ; Child ; Female ; Hepatitis, Autoimmune ; Humans ; Immunoglobulin G ; blood ; Liver Transplantation ; adverse effects ; Male

Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea. Mannose-binding lectin (MBL) initiates the lectin complement activation pathway following oxidative stress and plays an important role in the regulation of inflammatory processes. To determine whether there is a genetic association between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic exposed controls (AECs) and 144 unexposed normal controls were enrolled in this study. Three polymorphisms (-554 G>C, - 431A>C and - 225 G>C) in the MBL2 promoter were genotyped, and serum MBL levels were determined by enzyme-linked immunosorbent assay. Functional variabilities in the promoter polymorphisms were analyzed by a luciferase reporter assay and electrophoretic mobility shift assay (EMSA). A significantly higher frequency of haplotype (ht) 2 [CAG] was noted in the DI-OA group compared with the AEC group (P=0.044). The patients with DI-OA carrying ht2 [CAG] had significantly lower PC20 methacholine levels (P<0.001) than the non-carriers. The serum MBL levels were significantly higher in the DI-exposed subjects (both the DI-OA patients and AECs) carrying ht1 [GAG] (P=0.028). Luciferase activity was significantly enhanced in ht1 [GAG] compared with ht2 [CAG] in human hepatocarcinoma cells (Hep3B) (P=0.002). The EMSA showed that a - 554G probe produced a specific shifted band compared with the - 554C probe. These findings suggest that decreased serum MBL levels due to polymorphisms of the MBL2 gene may increase susceptibility to the development of DI-OA in DI-exposed individuals.
Adult ; Alleles ; Asthma, Occupational/diagnosis/*etiology ; Cell Line ; Female ; Forced Expiratory Volume ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Immunoglobulin E/immunology ; Immunoglobulin G/immunology ; Isocyanates/*adverse effects/immunology ; Male ; Mannose-Binding Lectin/blood/*genetics ; Middle Aged ; *Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Protein Binding ; Transcriptional Activation ; Young Adult

BACKGROUND/AIMS: The treatment for steroid-refractory acute graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) needs to be standardized. We report our clinical experience with etanercept for steroid-refractory acute GVHD. METHODS: Eighteen patients who underwent allo-SCT and presented with steroid-refractory acute GVHD at Ajou University Hospital were studied retrospectively. They were given 25 mg of etanercept subcutaneously twice weekly for 4 weeks. The clinical responses were evaluated with regard to the severity of acute GVHD. RESULTS: The median patient age was 43.5 years. Using nonparametric tests, etanercept had a down-grading effect on acute GVHD (p = 0.005), although no patient experienced complete remission. Partial responses were seen in 80%, 17%, and 57% of grade II to IV patients, respectively. Skin and gut GVHD were well controlled with etanercept, whereas hepatic GVHD was not. Four patients died of fatal infections. No factors affecting the clinical outcome of etanercept were identified. CONCLUSIONS: Etanercept has a modest effect on steroid-refractory acute GVHD after allo-SCT, with tolerable side effects.
Acute Disease ; Adult ; Aged ; Allografts ; Female ; Graft vs Host Disease/etiology/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunoglobulin G/adverse effects/*therapeutic use ; Immunosuppressive Agents/adverse effects/therapeutic use ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor/*therapeutic use ; Retrospective Studies ; Steroids/therapeutic use ; Young Adult

Drug-induced immune haemolytic anaemia (DIIHA) is extremely rare. We herein report a case of life-threatening DIIHA due to levofloxacin. This is the second case reported in the literature. A 51-year-old woman presented with complaints of fatigue after 4-5 days of levofloxacin therapy for a lung infection. At presentation, she was found to have haemolysis with a positive Coombs test and IgG autoantibodies. Levofloxacin was identified as the probable culprit, using the Naranjo adverse drug reaction probability scale. Upon discontinuation of the drug and initiation of steroids, the patient's haematological parameters stabilised. Diagnosis of DIIHA is made through a history of intake of levofloxacin, clinical and laboratory features of haemolysis and a positive Coombs test. An autoantibody screen is most commonly positive for warm antibodies (IgG type). It is essential for clinicians to recognise this rare complication caused by a commonly prescribed medication, discontinue the offending drug and initiate treatment.
Anemia, Hemolytic ; chemically induced ; Anti-Bacterial Agents ; adverse effects ; therapeutic use ; Autoantibodies ; blood ; Female ; Fluoroquinolones ; adverse effects ; Hemolysis ; Humans ; Immunoglobulin G ; blood ; Levofloxacin ; adverse effects ; Male ; Middle Aged ; Steroids ; therapeutic use

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFalpha inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFalpha therapy in patients with TNFalpha-associated TB. We used data of 1,012 patients with RA or AS treated with TNFalpha inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-gamma releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFalpha therapy. All patients discontinued TNFalpha inhibitors with starting the treatment of TB. Eight patients were re-administered TNFalpha inhibitors due to disease flares and promptly improved without recurrence of TB. TNFalpha inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Humans ; Hydroxychloroquine/adverse effects/therapeutic use ; Immunoglobulin G/adverse effects/therapeutic use ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Interferon-gamma Release Tests ; Male ; Methotrexate/adverse effects/therapeutic use ; Middle Aged ; Mycobacterium tuberculosis/isolation & purification ; Receptors, Tumor Necrosis Factor/therapeutic use ; Retrospective Studies ; Spondylitis, Ankylosing/*drug therapy ; Tuberculin Test ; Tuberculosis/*chemically induced/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

PURPOSE: Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. CONCLUSION: The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients.
Adolescent ; Adult ; Aged ; Anaphylaxis/*chemically induced/immunology ; Anti-Bacterial Agents/adverse effects/*immunology ; Antigens, CD63 ; Basophils/metabolism ; Cefaclor/*adverse effects/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hypersensitivity, Immediate/chemically induced/diagnosis/*immunology ; Immunoglobulin E/*blood ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Retrospective Studies ; Skin Tests ; Urticaria/chemically induced/diagnosis/immunology ; Young Adult