Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis

The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16-72), with various types of glomerulonephritis. Forty-nine healthy blood donors, mean age 41 years (range 19-65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria. The serum immunoglobulin patterns were different for the various clinical groups of patients. Patients with Wegener's granulomatosis, rapidly progressive glomerulonephritis and SLE had a significant increase in total IgG and of IgG4 (P less than 0.05-0.001). Patients with minimal change disease had low concentrations of IgG (P less than 0.001) with a significant decrease in IgG1 and IgG2 (P less than 0.001 and 0.01, respectively). Highly significant increases in IgA were noted for patients with IgA nephritis (P less than 0.001) but high levels were also seen in patients with chronic glomerulonephritis. The findings might have diagnostic implications.     

孕妇IgG抗体效价的检测新方法探讨

目的:探讨在孕妇IgG抗体效价的检测预处理过程中不加入2-巯基乙醇(2-Me)处理液是否可行。方法:检测孕妇IgM和IgG抗体效价,对试验结果进行比较。结果:IgG抗体效价通常高于IgM抗体效价,IgM抗体效价通常在1∶64以下,IgM和IgG抗体在抗体效价检测过程中有协同凝集作用。结论:可以对IgM抗体效价通常在1∶64以下孕妇不用2-Me处理液处理直接检测IgG抗体效价,对个别IgM抗体效价通常在1∶64以上,IgG抗体效价未超过同一孕妇IgM抗体效价者则需要进行预处理。     

Differential regulation of IgG subclasses and IgE antimalarial antibody responses in complicated and uncomplicated Plasmodium falciparum malaria

The aim of this study was to assess the immunoglobulin (Ig)-subclass distribution of antimalarial antibody responses in 110 and 169 Thai patients with complicated and uncomplicated Plasmodium falciparum malaria, respectively. Antimalarial plasma IgG subclasses and IgE antibody levels against a crude malaria blood stages, and antigen preparation were determined using enzyme-linked immunosorbent assay (ELISA). On admission, the levels of anti-P. falciparum IgG1, IgG2 and IgG3 were significantly lower in patients with complicated malaria than uncomplicated malaria (IgG1, P < 0.0001; IgG2, P < 0.0001; IgG3, P < 0.0001). The levels of antimalarial IgE were slightly lower, but not statistically significant (P = 0.389) in the complicated malaria. After adjusting all antibody levels and age, anti-P. falciparum IgG3 levels remained significantly associated with complicated malaria. None of the other antibody concentrations showed statistically significant associations with complicated malaria. The anti-P. falciparum IgG3 levels were related to the IgG1 as well as IgG2 levels. A correlation between anti-P. falciparum IgG2 and IgE was observed in the complicated malaria group, and this may indicate their roles in the severity of disease. Our data suggest that anti-P. falciparum IgG3 is associated with a reduced risk of complicated malaria and that antimalarial Ig-subclasses are differently regulated in patients with complicated and uncomplicated malaria.     

Type-specific anti-pneumococcal antibody subclass response to vaccination after splenectomy with special reference to lymphoma patients

The IgG and IgA antibody subclass responses to pneumococcal polysaccharide antigens type 6A and 19F were studied after immunization with a 14-valent vaccine (Pneumovax, MSD), in 53 splenectomized patients (11 Hodgkin's disease, 13 nonHodgkin's lymphoma (NHL), 9 immune haemolytic anaemia or idiopathic thrombocytopenia purpura and 20 posttraumatic splenectomized patients) and 18 non-splenectomized controls. The antibodies were mainly restricted to the IgG2 and IgA2 subclasses. NHL patients had lower pre-vaccination values to the studied antigens and lower antibody response to vaccination than the other patient groups in which the antibody responses did not differ from those of controls. 1 vaccinated NHL patient experienced two episodes of pneumococcal septicaemia, both occurring after chemotherapy which abolished the previously normal IgG2 antibody levels to the pneumococcal antigens. It is concluded that the antibody response to 6A and 19F antigens after pneumococcal vaccination is not reduced in splenectomized patients but is impaired in immunodeficiency states associated with B-cell lymphoma and treatment with cytostatic drugs.     

Knowledge and beliefs about influenza,pneumococcal disease,and immunizations among older people

OBJECTIVES: Despite the burden of disease caused by influenza and pneumococcus, immunization rates are moderate and have not reached national goals set for 2010. This study's objective was to identify patient knowledge, attitudes, and beliefs that serve as facilitators of and barriers to influenza and pneumococcal vaccination. DESIGN: A survey conducted in 2000 by computer-assisted telephone interviewing. SETTING: To encounter a broad spectrum of patients and healthcare systems, we sampled patients at inner-city health centers, Department of Veterans Affairs outpatient clinics, and rural and suburban practices. PARTICIPANTS: Inclusion criteria were patients aged 66 and older and an office visit after September 30, 1998. MEASUREMENTS: Responses to questionnaire. RESULTS: Overall, 1,007 (82%) interviews were completed among 1,234 people contacted by phone. Vaccination against pneumococcal disease was significantly related to being able to accurately describe one or more classic symptoms of pneumonia (P =.05). Vaccination against influenza and pneumococcal disease was significantly related to belief that vaccination was the best way to prevent these diseases (P <.001). The unvaccinated reported that they felt they were not likely to contract influenza and that they did not know they needed the pneumococcal vaccine. Access was not related to vaccination status. CONCLUSIONS: Educational campaigns to increase vaccination rates among older adults should focus on symptoms of, risk for, and severity of influenza and pneumococcal diseases and encouraging physicians to recommend the vaccines to their patients.     

Semiquantitative measurement of IgG subclasses and IgM of platelet-specific antibodies in a glycoprotein-specific platelet-antigen capture assay

The detection of platelet-specific antibodies is of high clinical interest in diseases with immune thrombocytopenia. The glycoprotein-specific platelet-antigen capture (PAC)-assay developed in this study is especially suited to the differentiation of platelet-specific immunoglobulin (Ig) G subclasses and the determination of platelet-specific IgM in serum or on platelets. The problems with unspecific signals or low sensitivity usually seen with the detector antibodies available are effectively overcome, as unbound detector antibodies are removed at an early stage in the assay. We investigated 14 maternal alloantisera from cases of neonatal alloimmune thrombocytopenia (NAITP) and six sera from patients with autoimmune thrombocytopenic purpura (AITP). In NAITP sera, we found IgG1 alone in 57%, IgG1 + IgG3 in 21% and IgG1 + IgG2 in 14% of cases. One serum contained IgG1 + IgG2 + IgG3. In AITP, three out of the six sera contained IgG1 alone. One serum contained IgG1 + IgG2. One patient, with highly refractory AITP, had platelet-specific IgG1 + IgG2 + IgG3 in his serum. A patient with AITP in remission and normal platelet counts only showed platelet-bound IgG2. The detection of platelet-specific 'whole IgG' is possible too. However, at this time the commonly used monoclonal antibody-specific immobilization of platelet antigens (MAIPA) method should not be replaced for this purpose, as it is well standardized and used with similar results in many laboratories. The PAC assay sensitively detects the subclasses of platelet-specific IgG and human leucocyte antigen (HLA)-antibodies independently. It is easy to perform and takes less time than other platelet glycoprotein-specific methods.     

Barriers to pneumococcal and influenza vaccination in older community-dwelling adults (2000-2001)

OBJECTIVES: To identify facilitators of and barriers to vaccination in patients from a range of socioeconomic levels. DESIGN: A survey was conducted in 2001 using computer-assisted telephone interviewing. SETTING: Patients from inner-city health centers and suburban practices were interviewed. PARTICIPANTS: Inclusion criteria were aged 66 and older and an office visit after September 30, 1998. MEASUREMENTS: Self-reported influenza and pneumococcal vaccination status and facilitating conditions, attitudes, social influences, and perceived consequences from the Triandis model were assessed. RESULTS: Overall, 557 interviews were completed with 775 eligible patients (72%). Patients who reported having received pneumococcal vaccine more frequently believed that their physicians recommended the vaccine than did the unvaccinated (97% vs 49%; P=.001). This was also true for influenza vaccine (99% vs 80%; P<.001). More unvaccinated patients than vaccinated patients felt that obtaining either vaccine was more trouble than it is worth (pneumococcal 19% vs 1%; P=.04, influenza 20% vs 1%; P=.004). The vaccinated were more likely to be willing to obtain the influenza and pneumococcal vaccines at the same time (pneumococcal 91% vs 59%; P=.002, influenza 91% vs 55%; P=.014). CONCLUSION: Physicians should take every opportunity to recommend vaccination to their eligible adult patients. Offering influenza and pneumococcal vaccines at the same visit is an acceptable means to ensure that adults are fully vaccinated.     

IgG subclasses of anti-FVIII antibodies during immune tolerance induction in patients with hemophilia A

The eradication of inhibitory antibodies in patients with haemophilia A can be accomplished by frequent administration of high or intermediate doses of factor VIII (FVIII), so-called immune tolerance induction (ITI). This study monitored the distribution of IgG subclasses of anti-FVIII antibodies during ITI. FVIII-specific antibodies of subclass IgG1 were detected in all inhibitor patients tested, anti-FVIII IgG4 in 16, IgG2 in 10 and IgG3 in one of 20 patients analysed. Levels of anti-FVIII IgG1 and IgG4 correlated well with inhibitor titres as measured by Bethesda assay. In low-titre inhibitor patients, anti-FVIII antibodies consisted primarily of subclass IgG1 whereas, anti-FVIII antibodies of subclass IgG4 were more prominent in patients with high titre inhibitors who needed prolonged treatment or who failed ITI. Longitudinal analysis of 14 patients undergoing ITI revealed that the relative contribution of IgG subclasses was constant for most of the patients analysed. In two patients, the relative contribution of IgG4 increased during ITI. Overall, our findings document the distribution and dynamics of anti-FVIII IgG subclasses during ITI. Future studies will need to address whether monitoring the relative contribution of anti-FVIII subclasses IgG1 and IgG4 may be useful for the identification of patients who are at risk of failing ITI.     

Cytokine profile and insulin antibody IgG subclasses in patients with recent onset Type 1 diabetes treated with oral insulin

Aims/hypothesis Tolerance to orally administered antigens may be generated through the induction of T helper cell type 2 and 3 (Th2/Th3) regulatory cells. We previously reported that treatment of recent onset Type 1 diabetes with oral insulin had no effect on residual beta cell function. The aim of this study was to evaluate whether this treatment produces a deviation in the immune response, with polarisation of the cytokine pattern and the induction of a Th2-like antibody response.Methods Mononuclear cells were collected from a total of 20 patients with Type 1 diabetes before and after 12 months of treatment with oral insulin (n=11) or placebo (n=9). Following stimulation of the cells with insulin or phytohaemagglutinin, levels of Th2 and Th3 cytokines (including TGF-, IFN-, IL-4 and IL-5) in the culture supernatants were assessed by ELISA. In addition, levels of total and specific insulin antibody IgG subclasses were measured by radioimmunoassay in serum samples drawn from 33 patients with Type 1 diabetes before and after 3, 6 and 12 months of therapy with oral insulin (n=18) or placebo (n=15).Results After 12 months of treatment, the release of TGF- was significantly higher in patients who received oral insulin compared with those who received placebo (p=0.025 and p=0.006 for lymphocytes challenged with insulin and phytohaemagglutinin respectively). The two groups had similar levels of IL-4 and IL-5 both at baseline and after 12 months of treatment. The release of IFN- was markedly reduced in patients treated with oral insulin compared with those who received placebo at the 12-month follow-up. Circulating levels of IgG1 and IgG3 subclasses directed against insulin were significantly lower in the oral insulin group than in the placebo group after 12 months of treatment (p=0.05 for IgG1 and p=0.014 for IgG3).Conclusions/interpretation The increased TGF- release observed in patients treated with oral insulin suggests that a regulatory response can be induced in vivo by this treatment. The lower levels of insulin antibody IgG1 and IgG3 subclasses present in patients exposed to oral insulin are consistent with a Th2 deviation of the immune response. The failure of oral insulin treatment to provide any measurable clinical benefit may be due to the timing of treatment initiation.     

The IgG subclasses of platelet-associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

The majority of patients with idiopathic thrombocytopenic purpura (ITP) have antiplatelet autoantibodies that are most frequently directed against platelet glycoproteins IIb/IIIa or Ib/IX/V. However, there is some debate whether the immune response is oligoclonal or polyclonal in nature. We investigated the subclass distribution of anti-IIb/IIIa IgG autoantibodies in 59 prospectively studied patients with ITP. We also tested patients with a variety of thrombocytopenic disorders (n=31) and healthy controls (n=30). Platelet lysates were tested for IgG anti-IIb/IIIa autoantibodies, and the specific IgG subclass distribution was measured using antigen capture assays. All testing was done blinded to diagnosis and other assay results. After unblinding, we found that 43 of the 59 ITP patients had anti-IIb/IIIa autoantibodies (sensitivity=73%). Anti-IIb/IIIa autoantibodies were also detected in five of the 31 non-ITP patients, but in none of the 30 healthy controls (specificity=91%). The IgG subclass assay was positive in 39 of the 43 ITP patients with anti-IIb/IIIa antibodies (sensitivity=92%) and in 12 samples that had no detectable anti-IIb/IIIa antibodies including two ITP patients (specificity=83%). The most common subclass in the ITP patient samples was IgG1 (77%), either alone (n=14) or with other IgG subclass antibodies (n=19). However, there were also patients with only IgG2 (n=2), IgG3 (n=3) or IgG4 (n=3) antibodies. Our results are consistent with the hypothesis that ITP is a heterogeneous disorder and that some patients have evidence of oligoclonality, whereas other patients have polyclonal autoantibodies.     

Pattern of platelet-associated immunoglobulin (classes and IgG subclasses) in childhood immune thrombocytopenic purpura

Platelet-associated Ig classes and IgG subclasses were studied by a semiquantitative platelet ELISA test in 17 children with immune thrombocytopenic purpura (ITP). An elevation of PAIg was found in 94% of the children. In nearly all cases increased amounts of PAIgG of subclass G1 was seen, and in half of the cases increased amounts of PAIgM were also seen. No statistical difference in the composition of PAIg classes and PAIgG subclasses in acute and in chronic ITP was found. However, a correlation of increased amount of PAIgG3 and very low platelet count (20 x 10(9)/l) was observed.     

Safety of pneumococcal revaccination

Indications for pneumococcal polysaccharide revaccination include highest-risk patients vaccinated more than six years previously, but there is controversy regarding revaccination of patients with chronic medical conditions and revaccination of the elderly. The object of the study was to investigate whether revaccination with the pneumococcal polysaccharide vaccine would cause significant adverse reactions. 151 patients were revaccinated and completed a questionnaire concerning the 72 hours after the injection. Valid data were obtained from 127 patients. Mild systemic reactions varied from 4% to 8% and local reactions varied from 40% to 60%, which is not different from the reported reaction with the initial vaccination. This profile of adverse reactions after revaccination should minimize concerns about revaccination. Received from the Allergy/Immunization Clinic, Fitzsimons Army Medical Center, Aurora, Colorado. Presented at the annual meeting of the American College of Allergy and Immunology, November 8, 1994, San Francisco, California. No grant or financial support was received.     

Influenza season triggers pneumococcal vaccination

OBJECTIVES: To investigate the frequency with which influenza and pneumococcal vaccines are administered alone and together. DESIGN: Retrospective review. SETTING: Marshall University internal medicine practice, Huntington, West Virginia. PARTICIPANTS: All patients aged 65 and older seen in the practice from 1999 through 2005 who received pneumococcal or influenza vaccine. MEASUREMENTS: Billing records were reviewed for administration of pneumococcal and influenza vaccines to Medicare beneficiaries, and rates of administration of these vaccines given alone and together were calculated. RESULTS: Nine hundred sixty-nine doses of pneumococcal vaccine were administered. Of these, 796 (82%) were administered during the fall and winter. Three hundred fifty-six (45%) pneumococcal vaccinees received it together with influenza vaccine. During 2001 and 2005, when influenza vaccine supply was limited, the rate of pneumococcal vaccine administered together with influenza vaccine declined sharply. Nonetheless, the rate of pneumococcal vaccination remained relatively stable because of an increase in the rate of vaccine administered alone. CONCLUSION: Four-fifths of pneumococcal vaccine was administered in the fall and winter, and approximately half was given together with influenza vaccine. When influenza vaccine was in limited supply, physicians continued to vaccinate with pneumococcal vaccine alone. These findings suggest that the imminent influenza season provides the trigger for physicians to prescribe pneumococcal vaccine. Physicians should be reminded that pneumococcal vaccine can be administered any time of year.     

Rate of Interaction of IgG1 and IgG3 Sensitized Red Cells with Monocytes in the Phagocytosis Assay

Another aspect of the preferential binding to monocytes of IgG3-coated erythrocytes over IgG1-coated erythrocytes has been demonstrated by measuring the rate of interaction in the phagocytosis assay. Erythrocytes sensitized with comparable numbers of IgG1 and IgG3 monoclonal and polyclonal anti-D antibodies were incubated with a monocyte preparation for up to 2 h. Interaction with the erythrocytes sensitized with monoclonal or polyclonal IgG3 was much more rapid than with erythrocytes sensitized with IgG1. With IgG3-sensitized erythrocytes maximum interaction was found after 30 min, whereas with IgG1-sensitized erythrocytes 2 h were required for maximum interaction. These results are consistent with the longer hinge region of IgG3 allowing bridges to be formed more easily between the negatively charged erythrocytes and monocytes.     

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.     

Adult immunization in university-based primary care and specialty practices

The purpose of this study was to assess vaccination status of adults in primary and specialty care practices in a retrospective review of medical records from 1997 to 2000 at one university medical center. Eligible patients were aged 50 and older and had two or more visits to primary and specialty care practices (N=14,556). Outcomes were receipt of pneumococcal vaccine once, tetanus booster within 10 years, and influenza vaccine in 2 of the 3 years. Vaccination rates for patients aged 65 and older were 59% for pneumococcal, 51% for tetanus, and 32% for influenza. Asians, Latinos, and African Americans were more likely than whites to have received influenza, pneumococcal, or tetanus vaccinations. Patients seen in primary care (41%) or in both primary care and specialty practices (42%) were more likely to receive adequate vaccination than those in specialty practices (17%) (P<.001). For pneumococcal vaccinations, relative to patients receiving specialty care only, patients receiving primary care only had an adjusted odds ratios (OR) of 6.6 (95% confidence interval (CI)=5.6-7.7) and patients in both primary care and specialty care had an OR of 7.2 (95% CI=6.2-8.3). For influenza, the corresponding ORs were 3.9 and 4.8, respectively, and for tetanus, 4.6 and 5.2. Patients who received care only from specialty practices were less likely than those with some primary care to receive adequate adult vaccinations. With the exception of Russian immigrants, the study did not find that racial and ethnic minorities had lower rates of vaccination than whites.     

Antibody Response to Pneumococcal Vaccination in Patients with Myelomatosis

17 patients with myelomatosis were vaccinated with a 14-valent pneumococcal capsular polysaccharide vaccine. In comparison to 12 healthy controls, they had statistically significant lower combined geometric mean antibody concentrations (the geometric means of all 14 antigens), both before and 4 weeks after the immunization. Mean antibody increases, however, were remarkably similar in the 2 groups. After 18 months the geometric mean antibody concentrations of the patient group had returned to preimmunization levels or lower for 7 out of 14 antigens. 1 case of pneumococcal bacteraemia occurred in the patient group 8 1/2 months after vaccination in spite of a significant initial antibody response against the infecting serotype 23 F. Pneumococcal vaccination in patients with myelomatosis appears to yield subnormal antibody responses and therefore probably insufficient protection against pneumococcal infection.     

Influence of prior pneumococcal and influenza vaccination on outcomes of older adults with community-acquired pneumonia

OBJECTIVES: To determine whether prior pneumococcal and seasonal influenza vaccination improves outcomes in older adults hospitalized for community‐acquired pneumonia (CAP). DESIGN: Prospective, observational, multicenter study. SETTING: Five public hospitals providing universal free care to the whole population in three Spanish regions. PARTICIPANTS: Individuals aged 65 and older admitted to the hospital with CAP through the emergency department. MEASUREMENTS: Pneumococcal and influenza vaccination status. The primary study outcomes were intensive care unit (ICU) admission, length of hospital stay (LOS), and overall case‐fatality rate. Outcome variables of individuals vaccinated with both vaccines were compared with outcomes of those who were unvaccinated. RESULTS: Two hundred thirty‐eight individuals had received 23‐valent pneumococcal polysaccharide vaccine and seasonal influenza vaccination and were compared with 195 unvaccinated individuals. No differences were found with respect to combined antibiotic therapy between groups (38.0% vs 39.7%; P=.80). Similar percentages of vaccinated and unvaccinated individuals required ICU admission (7.2% vs 8.2%; P=.69). Mean LOS was significantly shorter in vaccinated individuals (9.9 vs 12.4 days; P=.04). Overall case‐fatality rates were similar in both groups (5.9% vs 5.1%; P=.73). After adjustment, LOS, risk of ICU admission, and overall case‐fatality rate were not associated with prior pneumococcal and seasonal influenza vaccination. CONCLUSION: The clinical outcomes of vaccinated older adults hospitalized with CAP were not better than those observed in unvaccinated individuals.