IgG₄ is a subclass of IgG. Elevated serum IgG₄ levels are an important serological feature of IgG₄ related diseases and serve as a serological marker for assessing disease activity and severity. The harmonization of IgG₄ detection is crucial for its clinical application. National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), Experimental Diagnosis Research Committee, Rheumatology and Immunology Physicians Committee of Chinese Medical Doctor Association, Autoantibodies Detection Committee, and Chinese Rheumatism Data Center have organized clinical and laboratory experts to draft this consensus, aiming to standardize IgG₄ detection and provide guideline for clinician and laboratory experts to appropriate utility and interpret IgG₄ results in China.
Humans ; China ; Consensus ; Immunoglobulin G/blood*

OBJECTIVE: To investigate the role of multiple serological methods in the identification of complex antibodies. METHODS: The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies. RESULTS: The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jk^a antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jk^a and anti-Fy^a antibodies. CONCLUSION It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jk^a and anti-Fy^a antibodies exist in the patient's serum by multiple serological methods.
Humans ; Papain ; Blood Group Antigens ; Erythrocytes ; Immunoglobulin G ; Immunoglobulin M

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 pandemic. The first case of COVID-19 was reported at early December in 2019 in Wuhan City, China. To examine specific antibodies against SARS-CoV-2 in biological samples before December 2019 would give clues when the epidemic of SARS-CoV-2 might start to circulate in populations. We obtained all 88,517 plasmas from 76,844 blood donors in Wuhan between 1 September and 31 December 2019. We first evaluated the pan-immunoglobin (pan-Ig) against SARS-CoV-2 in 43,850 samples from 32,484 blood donors with suitable sample quality and enough volume. Two hundred and sixty-four samples from 213 donors were pan-Ig reactive, then further tested IgG and IgM, and validated by neutralizing antibodies against SARS-CoV-2. Two hundred and thirteen samples (from 175 donors) were only pan-Ig reactive, 8 (from 4 donors) were pan-Ig and IgG reactive, and 43 (from 34 donors) were pan-Ig and IgM reactive. Microneutralization assay showed all negative results. In addition, 213 screened reactive donors were analyzed and did not show obviously temporal or regional tendency, but the distribution of age showed a difference compared with all tested donors. Then we reviewed SARS-CoV-2 antibody results from these donors who donated several times from September 2019 to June 2020, partly tested in a previous published study, no one was found a significant increase in S/CO of antibodies against SARS-CoV-2. Our findings showed no SARS-CoV-2-specific antibodies existing among blood donors in Wuhan, China before 2020, indicating no evidence of transmission of COVID-19 before December 2019 in Wuhan, China.
Humans ; Antibodies, Viral ; Blood Donors ; China/epidemiology* ; COVID-19/immunology* ; Immunoglobulin G ; Immunoglobulin M ; Pandemics ; SARS-CoV-2

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q₁ to Q₄ according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q₁, subjects in group Q₄ with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q₄ with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q₄ with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (P_trend=0.018, P_trend=0.010) and increased with the increase of serum IgA concentrations (P_trend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, P_trend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.
Humans ; Adult ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Blood Glucose ; Inflammation/complications* ; Immunoglobulin A ; Immunoglobulin M ; Immunoglobulin G ; Immunoglobulin E ; Risk Factors

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q₁ to Q₄ according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q₁, subjects in group Q₄ with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q₄ with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q₄ with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (P_trend=0.018, P_trend=0.010) and increased with the increase of serum IgA concentrations (P_trend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, P_trend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.
Humans ; Adult ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Blood Glucose ; Inflammation/complications* ; Immunoglobulin A ; Immunoglobulin M ; Immunoglobulin G ; Immunoglobulin E ; Risk Factors

OBJECTIVE: To establish a based method flow cytometry to identify the antigen Jka in human red blood cells (RBCs) and verify its accuracy. METHODS: A total of 96 blood samples were enrolled in the study randomly from the voluntary blood donors in Shenzhen Blood Center. The RBCs were incubated with IgG anti-Jka primary antibody, and then labeled with the secondary antibody anti-IgG-Alexa Fluor 647. The fluorescence histograms of each sample were obtained by flow cytometry. Serological agglutination test was used to compare the accuracy of flow cytometry in the detecting of antigen Jka, while PCR-SSP and gene sequencing genotyping were used to verify the accuracy of flow cytometry in the detecting of the antigen in human RBCs. RESULTS: The results of flow cytometry for antigen Jka in human RBCs were consistent with those from serological tests. Samples that demonstrated higher serological agglutination intensity also showed higher fluorescence activity, which indicate more stronger of Jka antigen. The sensitivity of flow cytometry was higher than that of serological test; especially in distinguish Jka weak and negative samples. Flow cytometric results of all samples were consistent with the genotyping results, which confirmed the accuracy of flow cytometry. CONCLUSION The study established a new flow cytometry-based method successfully for the identification of Jka antigen of Kidd blood group in human RBCs. The Kidd blood group antigen Jka of different intensities can be accurately distinguished by the technique.
Blood Group Antigens ; Blood Grouping and Crossmatching ; Erythrocytes ; Flow Cytometry ; Humans ; Immunoglobulin G ; Kidd Blood-Group System

OBJECTIVE: To investigate the titer of IgG anti-A/B erythrocyte antibody in vivo of the neonate with hemolytic disease of newborn(HDN), and explore its clinical valua in evaluating the severity of HDN. METHODS: 300 neonates with HDN, 50 neonates with neonatal hyperbilirubinemiain and 50 healthy neonates were selected as research object and Microtubes Gel Test was used to detect the titer of IgG anti-A/B erythrocyte antibody in vivo. Their clinical data and their mothers' prenatal examination data were retrospectively analyzed. Three hemolysis tests (direct antiglobulin test, free antibody test and release test), irregular antibody screening, and the titer of IgG anti-A/B blood group antibody was determined by serological method. Red blood cells(RBC), hemoglobin(Hb), reticulocytes(Ret) and nucleated red cells were detected by hematology analyzer. Indirect bilirubin and albumin(Alb) were detected by biochemical analyzer. The relationship between the titer of IgG anti-A/B erythrocyte antibody in vivo and the severity of HDN was analyzed. RESULTS: There were six serological diagnosis modes in the HDN group,the difference between modes was statistically significant (P<0.05). The antibody titer relationship between HDN neonates and pregnant women was positive correlation(r=0.8302). The highest antibody titer of release test and free antibody test were 1∶32 and 1∶2, and the difference was statistically significant（P<0.05）. RBC, Hb and Alb in HDN patients were lower than those in neonatal hyperbilirubinemia patients and healthy neonates (P<0.05), and were negatively relevant with antibody titer in vivo (r=-0.8016). Bilirubin content in HDN patients were higher than those in neonatal hyperbiliru binemia patients and healthy neonates group(P<0.05), and was positively relevant with antibody titer in vivo (r=0.8731). The hospital day in HDN patients was significantly relevant with the antibody titer in vivo (r=0.8547), but not with the age, sex, weight and ABO blood types (P>0.05). CONCLUSION The detection of antibody titer in HDN patients can be used to evaluate the antibody concentration in vivo, predict the ability of antibody to induce erythrocyte hemolysis, and help to judge the serenrity and prognosis of HDN.
ABO Blood-Group System ; Bilirubin ; Blood Group Incompatibility ; Erythroblastosis, Fetal ; Erythrocytes ; Female ; Hematologic Diseases ; Hemolysis ; Humans ; Immunoglobulin G ; Infant, Newborn ; Pregnancy ; Retrospective Studies

Objective: To summarize changes of serum immunoglobulin levels before and after chemotherapy in children with Burkitt lymphoma (BL), so as to investigate the effects of chemotherapy and rituximab on serum immunoglobulin levels in children with BL. Methods: Clinical data of 223 children with newly diagnosed Burkitt lymphoma at Beijing Children's Hospital from January 2009 to April 2017 were analyzed retrospectively. They were treated according to the modified LMB 89 regimen and some of them received combined rituximab therapy during the chemotherapy. The serum immunoglobulin (IgA, IgM, IgG) before chemotherapy, at the time of discontinuing chemotherapy, as well as 6, 12, 24, 36 months after chemotherapy were collected. Changes of serum IgA, IgM and IgG with time among different treatment groups were compared using repeated measures ANOVA. Results: According to risk group, 223 children were devided into group B（n=53）and group C（n=170）. Before chemotherapy, 109 cases (48.9%) were combined with hypogammaglobulinemia. The serum IgA, IgM, and IgG levels of all the patients were (0.9±0.7), 1.2 (0.5, 1.3) and (7.2±2.9) g/L before chemotherapy, (0.5±0.4), 0.2 (0.1, 0.3) and (6.3±2.3) g/L at the time of discontinuing chemotherapy (t=13.63, Z=-11.99, t=4.57, all P<0.05). There were statistical difference in IgA, IgM levels of group B and IgA, IgM, IgG levels of group C before chemotherapy and at the time of discontinuing chemotherapy (t=8.86, Z=-6.28, t=11.19, Z=-10.15, t=4.50, all P<0.05). The differences of serum IgA and IgG levels at the time after chemotherapy among patients treated with chemotherapy alone and those treated with chemotherapy combined rituximab in group B and C were significant (F=5.38, P=0.002 and F=4.22, P=0.007). Conclusions: Approximately half of children with BL have already existed hypogammaglobulinemia at initial diagnosis prior to the start of treatment. The modified LMB 89 regimen have significant effect on humoral immunity of children with BL. In the process of immune reconstruction after chemotherapy, rituximab has more significant effect on serum IgA and IgG levels in BL patients.
Agammaglobulinemia ; Burkitt Lymphoma/drug therapy* ; Child ; Humans ; Immunoglobulin A/blood* ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Retrospective Studies ; Rituximab/therapeutic use*

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

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test,
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Viral/blood* ; COVID-19/immunology* ; Carrier State/immunology* ; Child ; Child, Preschool ; China/epidemiology* ; Coronavirus Nucleocapsid Proteins/immunology* ; Cross-Sectional Studies ; Female ; Humans ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Male ; Middle Aged ; Occupations/classification* ; Phosphoproteins/immunology* ; SARS-CoV-2/immunology* ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus/immunology* ; Young Adult