Serum IgG Subclass Levels Research Articles

HIV-Associated Alterations of the Biophysical Features of Maternal Antibodies Correlate With Their Reduced Transfer Across the Placenta.

Human immunodeficiency virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV. The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies. The objective of this study was to assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer. Maternal serum IgG subclass levels, Fc glycosylation, Fc receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa. Maternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WWH, whereas digalactosylated and sialylated antibodies were reduced compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies. HIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer, potentially impairing antimicrobial immunity.

Overexpression of IgG2 in patients resembling IgG4-related disease with normal IgG4.

IgG4-Related Disease (IgG4-RD) results from tissue infiltration by IgG4-expressing plasma cells and lymphocytes, leading to fibrosis and organomegaly. Clinical presentation is remarkably variable according to organ involvement, and high IgG4 serum concentration, initially considered a diagnostic hallmark of IgG4-RD, tends to be forgone as an indispensable criterion for its diagnosis; it can indeed be absent in some patients, highlighting the diversity of presentation of this dysimmune condition. Nevertheless, elevation of IgG4 serum concentration in suggestive settings remains an argument in favour of IgG4-RD, and while other IgG subclasses can be elevated, this biological feature lacks any diagnostic value. We retrospectively studied 9 patients (5 females, 4 males, 31-81years old) for whom a diagnosis of IgG4-RD had been considered, based on clinical, imaging or histological criteria, but appeared to display abnormally high serum IgG2 while IgG4 levels were normal. Increased serum IgG1 in one case and increased IgG3 in another one were also noticed. Immunohistochemical analyses of intracellular immunoglobulins could be performed on tissue lymph node biopsies from 2 patients, which demonstrated strong infiltration with IgG2-expressing plasma cells. Thus, overexpression of IgG2 subclass may highlight cases of dysimmune disorders resembling IgG4-RD, although the disease trigger might be different, notably infectious. We suggest measuring all serum IgG subclass levels in patients with features consistent with IgG4-RD.

Humoral Immune Status in Relation to Outcomes in Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease, in which inflammation is thought to only play a secondary role. Several factors associated with acute exacerbations of IPF (AE-IPF) have been identified, including infections. This study investigated whether humoral immunodeficiency or increased inflammatory markers at diagnosis were associated with AE-IPF and survival. Four-hundred-and-nine patients diagnosed with IPF between 2011 and 2017 were retrospectively included. Immune status investigations at diagnosis included measurement of serum immunoglobulins (available in 38%), leukocyte and lymphocyte subsets in blood and bronchoalveolar lavage (BAL) fluid (available in 58%), as well as response to pneumococcal vaccination (available in 64%). Serum immunoglobulins or IgG subclass levels were below the lower limit of normal in 6%. The response to pneumococcal vaccination was severely impaired in 1%. Thirteen percent of patients developed an AE-IPF (4.7% per year). AE-IPF were associated with elevated lymphocytes in BAL fluid at diagnosis (p = 0.03). Higher serum IgA and IgG at diagnosis were associated with worse survival (p = 0.01; and p = 0.04), as were an increased BAL lymphocyte percentage (p = 0.005), and higher blood leukocytes and neutrophils (p = 0.01; and p = 0.0005). In a multivariate model, only BAL lymphocyte count retained statistical significance (p = 0.007). The prevalence of humoral immunodeficiencies was low in patients with IPF and not associated with AE-IPF or survival. Elevated lymphocytes in BAL were associated with the development of AE-IPF and worse survival. Higher serum immunoglobulins and immune cells in blood were also associated with worse survival. The local immune response in the lungs may be a target for future therapies.

Kinetics of IgG subclasses and their effects on the incidence of infection after allogeneic hematopoietic stem cell transplantation

BackgroundThe impact of the reconstitution of IgG subclasses after allogeneic hematopoietic cell transplantation (allo-HCT) on the outcomes is unclear. MethodsWe investigated the effects of stem cell source on the levels of serum IgG subclasses and their influence on the infection risk and prognosis. The levels of serum IgG, IgG2 and IgG4 were measured chronologically in 100 patients who underwent allo-HCT at our institute. ResultsThe median levels of serum IgG, IgA and IgM and the number of total B-cells were determined up to one year after allo-HCT. The serum IgG2 levels decreased within one year. A multiple linear regression analysis identified lymphoid malignancy, cord blood, and days after allo-HCT as significant risk factors for low serum IgG2 levels. There were no significant differences in the level of IgG or IgG2 at 90 days after allo-HCT between the late bacterial infection group (≥90 days following allo-HCT) and the control group (P = 0.34 and 0.45, respectively). There was no significant impact of the IgG, IgG2 or IgG4 levels on the survival or non-relapse mortality. ConclusionThe results suggest that cord blood transplantation might affect humoral immune reconstitution, including the IgG2 level, after allo-HCT.

Fusion-expressed CtxB-TcpA-C-CPE improves both systemic and mucosal humoral and T-cell responses against cholera in mice

BackgroundDevelopment of an effective oral vaccine against Cholera, a life-threatening dehydrating diarrheal disease, proved to be a challenging task. To improve oral subunit vaccine immunogenicity and to prevent the state of oral tolerance, application of mucosal adjuvants might be a promising approach. In the present study, the CtxB-TcpA-C-CPE fusion was constructed in which CtxB and C-CPE were used as mucosal adjuvants and vaccine delivery system, respectively, to induce mucosal immune responses, and to improve the anti-toxin and anti-colonizing immunity against V. cholerae. Materials & methodsThe fusion construct was synthesized, sub-cloned in pQE30 and expressed in E. coli. The three antigen, making the fusion protein, were also separately expressed in E. coli. The recombinant proteins were purified by affinity chromatography using Ni-NTA agarose. Western blot analysis using anti-His antibody was applied to confirm identity of the purified proteins. BALB/c mice were subcutaneously immunized with CtxB, TcpA, C-CPE and the fusion protein CtxB-TcpA-C-CPE separately. The mice were orally immunized (in 3 boosts) by the same vaccine. Mucosal immune response stimulation was evaluated by measuring the levels of intestinal IgA. Systemic immune response was evaluated by measuring total serum IgG, IgG1, IgG2a, IgG2b subclasses, and also IL-4, IL-5, IL-10 and IFN-γ cytokines in spleen cell culture. ResultsThe recombinant proteins CtxB, TcpA, C-CPE and the fusion protein CtxB-TcpA-C-CPE were expressed in E. coli and highly purified in a single step of chromatography. BALB/c mice immunized with the fusion protein had highest levels of intestinal IgA, serum IgG and IgG subclasses, compared to each of the three proteins making the fusion. Moreover, stimulated splenocytes of mice immunized with the fusion protein displayed significantly higher amounts of IL-5 and IFN-ɣ cytokines. Th2 dominance of the immune response was more evident in mice receiving the fusion protein. ConclusionInclusion of CtxB, as the mucosal adjuvant, and C-CPE, as the vaccine delivery system, in the fusion protein CtxB-TcpA-C-CPE significantly enhanced the elicited mucosal and systemic immune responses, compared to TcpA alone. Of note, significant production of intestinal IgA in mice immunized with the fusion protein is presumably capable of neutralizing TcpA, CtxB and C-CPE antigens, preventing V. cholera colonization, and toxic function of CtxB and C-CPE. Challenge infection of the immunized mice is required to evaluate protective potential of the fusion protein against V. cholera.

Reference ranges for serum immunoglobulin (IgG, IgA, and IgM) and IgG subclass levels in healthy children

Background/aimThe serum immunoglobulin levels are used routinely in clinical practice because they provide key information on the humoral immune status. This study aimed to determine the age-related reference values of serum immunoglobulin levels in healthy children.Materials and methodsA total of 330 healthy children, aged between 0 and 18 years, were included in this study. The serum immunoglobulin levels were measured using a nephelometric method in a total of 11 groups, each group consisting of 30 individuals, and IgG subclasses in 6 groups of children aged more than 2 years. ResultsThe serum IgG levels were high during the newborn period, decreased until the sixth month, and again increased to a maximum level at the age of 18 years. The level of IgA was found to be extremely low in the newborn period and then increased with age. While the lowest value was in the newborn period for serum IgM level, the highest value was in the 16- to 18-year-old period. The IgG subclasses varied depending on the age groups.ConclusionThe updated reference intervals of immunoglobulin levels in children may be used for the accurate diagnosis of immune deficiencies.

Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID).

Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n= 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6-85.7%) of patients with CVID. Conversely, a high IgE (> 180IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

BackgroundThe literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts.MethodsWe measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders.ResultsOne or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10–1.54, p < 0.01) and 1.19 (95% CI, 1.05–1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15–2.02, p < 0.01) and 1.33 (95% CI, 1.08–1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts.ConclusionsApproximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts.Trial registrationThis study used serum samples from participants of the MACRO (NCT00325897) and STATCOPE (NCT01061671) trials.

Altered immune responses in broiler chicken husbandry workers and their association with endotoxin exposure.

Exposure to bioaerosols in indoor animal farms associates with respiratory illnesses, but little is known about the immune modulation to chicken farmers. This study aimed to compare the general immunity of chicken farmers with those of control subjects with non-agricultural jobs. Blood taken from the farmers and controls was subjected to plasma IgE and IgG subclass measurements. Isolated peripheral blood mononuclear cells (PBMC) were stimulated and cytokine production was measured. Indoor total and respirable dust levels and their endotoxin (LPS) and aflatoxin (AF) levels in the farms were measured. In total, 29 chicken farmers on 19 farms and 14 age- and sex-matched office workers participated. Hematological differences were not observed. The farmers tended to have higher serum IgE and IgG subclass levels with significance for IgG1. The cytokines released by PBMC from farmers indicated skewing toward Type-2 helper T-cell responses: interferon (IFN)-γ:interleukin (IL)-4 and IFNγ:IL-13 ratios were significantly lower than for control PBMC. The farms had 707.1 EU/m3 LPS in total dust, and 15.8 EU/m3 LPS in respirable dust. Farmers exhibited immune skewing towards allergic immune responses that correlated with the LPS levels on their farms. Chicken farmers may be at risk of respiratory allergies due to occupational endotoxin exposure.

Evaluation of serum immunoglobulins concentrations and distributions in vitiligo patients.

Vitiligo is a dermatological disorder with an autoimmune mechanism characterized by production of a variety of autoantibodies. Different levels of immunoglobulins can indicate the presence and the stage of some autoimmune diseases. We aimed to investigate serum IgA, IgM and IgG subclass levels and melanocyte-reactive antibodies in 65 vitiligo patients by the immunonephelometric assay (35 healthy people as controls). Compared with normal controls, a significant increase in total IgG, IgG1 and IgG2 (p=.005, p=.003 and p=.043, respectively) was observed in progressive nonsegmental vitiligo patients. Also, we found a significant decrease in IgG3 (p=.000 and p=.023) in progressive nonsegmental vitiligo patients and segmental patients. Moreover, we found the serum levels of IgG4 subclass in stable nonsegmental patients were significantly higher than those in normal controls (p=.018). Compared with controls, the positive rates of melanocyte-reactive antibodies were higher in progressive nonsegmental patients and stable nonsegmental patients (p=.032 and p=.046, respectively). Furthermore, we found higher level of IgG4 and lower level of IgM in male than those in female. Higher IgG1 level was also observed in patients with a family history than in those without a family history. In addition, there was a significant inverse correlation between the concentrations of IgG4 and disease duration. Our evaluation about the level of immunoglobulins might provide a useful insight into the pathological process of vitiligo.

Association ofTLR3gene polymorphism with IgG subclass deficiency and the severity in patients with aspirin-intolerant asthma

Purpose: Toll-like receptor 3 (TLR3) recognizes to viral double-stranded RNA and is involved in antiviral defenses. A probable role of TLR3 gene variants in the pathogenesis of aspirin-intolerant asthma (AIA) has been suggested. AIA patients present more frequent asthma exacerbations in which respiratory viral infections could be an exacerbating factor. IgG subclass deficiency was commonly present with bronchial asthma. Based on previous findings, we investigated whether TLR3 variants could affect IgG3 subclass deficiency in AIA.Methods: We enrolled 279 AIA patients, 403 aspirin-tolerant asthma (ATA) patients, and 315 normal healthy controls (NC) in this study. TLR3 polymorphism at the promoter region -299698G>T was genotyped. The serum levels of IgG subclasses were determined by the single radial immunodiffusion method. Expressions of IgG3 and TLR3 on Epstein-Barr virus transformed-B cells isolated from asthmatic patients were evaluated by flow cytometry to investigate B-cell functions.Results: The TLR3 -299698 T allele was significantly associated with severity and IgG3 deficiency in the AIA group (P=0.044 and P=0.010, respectively), but not in the ATA group. IgG3 expression on B cells from asthmatics with IgG3 deficiency was significantly lower compared to those without (P=0.025). There was a positive correlation between IgG3 expression levels on B cells and serum IgG3 levels (r2=0.434, P=0.002).Conclusion: These results suggest that the TLR3 -299698G>T polymorphism may be associated with IgG3 subclass deficiency and severity in AIA. (Allergy Asthma Respir Dis 2016:4:264-270)

Serum IgG subclasses in autoimmune diseases.

To characterize serum IgG subclass levels in several autoimmune diseases, including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to analyze serum IgG subclass distribution and to test whether serum IgG4 levels are elevated in these diseases.Serum IgG subclass levels from 102 pSS, 102 SSc, 100 SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured using the immunonephelometric assay. The distribution of IgG subclasses among these autoimmune diseases was analyzed.In this cross-sectional study, serum IgG1 (IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There were no significant differences in the frequency of elevated serum IgG4 levels between patients and HC. In pSS, serum IgG1 levels were much higher than those in other disease groups, whereas serum IgG2 and IgG3 levels were most prominently increased in PBC.A strikingly different serum IgG subclass distribution was detected in patients with autoimmune diseases compared with HCs. Serum IgG subclass levels also showed distinct characteristics among different autoimmune diseases. Serum IgG4 levels in these patients were lower or not much higher than those in HCs, which differed from IgG4-related diseases.

Specific antibody deficiency with normal immunoglobulin concentration in children with recurrent respiratory infections

BackgroundResponse to polysaccharide antigens is a test to evaluate the immunological competence of children with recurrent respiratory infections (RRI) of unknown cause and no other immune system abnormality. In order to detect specific antibody deficiency (SAD), a group of children with RRI without other immunodeficiency were prospectively studied. MethodsWe included 20 children (12 male), age range 3–14 years, with six or more annual episodes of respiratory infections (RI); one or more monthly episodes of RI during the winter months; or three or more annual episodes of lower RI. The children were immunised with 23-valent polysaccharide anti-pneumococcal vaccine, and ELISA was used to measure anti-polysaccharide IgG antibody levels for 10 pneumococcal serotypes at baseline (T0), and 45 days (T1) and one year post-immunisation (T2). Post-immunisation response above 1.3μg/ml for more than 50% of the serotypes was considered normal for children 2–5 years, and for more than 70% of the serotypes in children older than 5 years. ResultsAt T1 19/20 children showed a normal response for their age, and only one patient showed a deficient response, suggestive of classic moderate SAD. At T2, 8/20 patients showed deficient responses, suggestive of impaired persistence of specific antibodies. There was a noteworthy association between deficient response and asthma and allergic rhinitis. ConclusionsWe propose first ruling out local or systemic causes, then performing serum immunoglobulin IgM, IgG, IgA, IgE and IgG subclass levels, and finally measuring response to polysaccharide pneumococcal antigens for detection of SAD.

Prognostic Implications of Elevated Serum IgE Levels in Primary Sclerosing Cholangitis

Purpose: Primary sclerosing cholangitis (PSC) is a prominent risk factor for cholangiocarcinoma (CCA), but reliable clinical biomarkers for predicting the risk of developing CCA are lacking. Recently, low serum IgE was found to be associated with CCA in a Japanese cohort of PSC patients. Our aim was to determine whether serum IgE levels predict the development of CCA and/or other adverse clinical outcomes in a United States-based cohort of PSC patients. Methods: Medical records of adult patients with well-defined PSC were retrospectively queried for serum IgE levels as well as other pertinent data, including age, sex, date of PSC diagnosis, IBD and immunosuppression status, biochemical markers of liver disease and other clinical variables and outcomes. The primary endpoint was time to developing adverse clinical endpoints including CCA, liver transplantation or death. Patients with low and high IgE (defined by sample median) were compared with respect to clinical characteristics using Mann-Whitney U and Fisher's exact test. Time to the development of adverse clinical endpoints in the low and high IgE groups was compared with Kaplan-Meier curves. The adjusted association between IgE and the primary outcome was assessed with multivariate proportional-hazards models. Results: Among the 38 patients included, the median age at PSC diagnosis was 41 years, 68% were male, 95% were non-Hispanic White and 89% had IBD. The median serum IgE was 47.6 kU/L, and median time from PSC diagnosis to IgE measurement was two weeks. The low and high IgE groups differed significantly only with respect to serum IgG levels and IgG1, IgG2 and IgG4 subclasses, all of which were higher in the high IgE group (all p<0.05). There was no significant difference in composite clinical endpoint-free (p=0.83, Figure) or CCA-free survival (p=0.20) between the low and high IgE groups. In multivariate analysis, only Mayo PSC risk score and MELD score were significant predictors of outcome (both p<0.05).Figure: Kaplan-Meier curves reveal no significant difference in the time to death, cholangiocarcinoma, or liver transplantation between the low and high IgE group (p=0.83).Conclusion: Serum IgE levels are associated with several serum IgG subclass levels, but do not appear to influence the time to development of CCA, LT or death in PSC patients from a United States-based cohort.

Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: A needle-free vaccination strategy

Here we report a new nanotechnology-based nasal vaccination concept intended to elicit both, specific humoral and cellular immune responses. The concept relies on the use of a multifunctional antigen nanocarrier consisting of a hydrophobic nanocore, which can allocate lipophilic immunostimulants, and a polymeric corona made of chitosan (CS), intended to associate antigens and facilitate their transport across the nasal mucosa. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the recombinant hepatitis B surface antigen (HB), were selected as model molecules for the validation of the concept. The multifunctional nanocarriers had a nanometric size (around 200nm), a high positive zeta potential (+45mV) and a high antigen association efficiency (70%). They also exhibited the ability to enter macrophages in vitro and to effectively deliver the associated imiquimod intracellularly, as noted by the secretion of pro-inflammatory cytokines (i.e. IL-6 and TNF-α). However, the nanocarriers did not induce the in vitro activation of the complement cascade. Finally, the positive effect of the co-delivery of HB and imiquimod from the nanocapsules was evidenced upon intranasal administration to mice. The nanocapsules containing imiquimod elicited a protective immune response characterized by increasing IgG levels over time and specific immunological memory. Additionally, the levels of serum IgG subclasses (IgG1 and IgG2a) indicated a balanced cellular/humoral response, thus suggesting the capacity of the nanocapsules to modulate the systemic immune response upon nasal vaccination.

THU0378 Interleukin-6 blocking therapy by tocilizumab in patients with multicentric castleman’s disease results in a significant decrease in serum levels of IgG4 and IGE

BackgroundMulticentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by systemic lymphadenopathy, constitutional inflammatory symptoms, and abnormal laboratories such as hyper-γ-globulinemia, increases in various auto-antibodies as well as acute...

Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia

Patients with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia who suffer from recurrent infections can be offered prophylactic intravenous immunoglobulin (Ig) substitution. Our aim was to assess the prevalence of pure IgG subclass deficiency (with normal Ig levels), its correlation to risk of infection, and the clinical value of routine measurement of serum IgG subclass levels in patients with CLL. Serum levels of Ig and IgG subclasses were determined in patients with CLL at Uppsala University Hospital. Clinical data were collected through patient records and questionnaires. Hypogammaglobulinemia occurred in 52.3% out of 111 patients. These patients did not have a higher annual risk of infection than patients without hypogammaglobulinemia (79.5% vs 79.1%, p = 0.706 for all infections; 13.4% vs 11.2%, p = 0.394 for severe infection; and 1.7% vs 3.4%, p = 0.083 for sepsis). Pure subclass deficiency was uncommon and occurred in 6 patients (5.4%). The annual overall risk of infection, of severe infection, and of sepsis for these patients did not differ as compared to patients with no hypogammaglobulinemia and no subclass deficiency (70.8% vs 80.7%, p = 0.334; 11.8% vs 11.1%, p = 0.497; and 8.9% vs 2.3%, p = 0.067, respectively). Pure IgG subclass deficiency is rare in patients with CLL. In this heterogeneous cohort of patients, neither hypogammaglobulinemia nor pure IgG subclass deficiency were significant risk factors for infectious complications. Measurement of serum levels of Ig may be justified in patients with recurrent severe infections, but routine analysis of IgG subclass levels in patients with CLL is probably not warranted.

Virus-Like Particles Containing the Tetrameric Ectodomain of Influenza Matrix Protein 2 and Flagellin Induce Heterosubtypic Protection in Mice

The ectodomain of matrix protein 2 (M2e) is highly conserved among influenza A viruses and can be a promising candidate antigen for a broadly cross-protective vaccine. In this study, a tetrameric M2e (tM2e) and a truncated form of flagellin (tFliC) were coincorporated into virus-like particles (VLPs) to enhance its immunogenicity. Our data showed that the majority of M2e in VLPs was presented as tetramers by introducing a foreign tetramerization motif GCN4. Intranasal immunization with tM2e VLPs significantly enhanced the levels of serum IgG and IgG subclasses compared to soluble M2e (sM2e) in mice. tM2e VLPs also induced higher M2e-specific T-cell and mucosal antibody responses, conferring complete protection against homologous influenza virus infection. The immunogenicity of tM2e VLPs was further enhanced by coincorporation of the membrane-anchored tFliC (tM2e chimeric VLPs) or coadministration with tFliC VLPs as a mixture, but not the soluble flagellin, inducing strong humoral and cellular immune responses conferring cross-protection against lethal challenge with heterotypic influenza viruses. These results support the development of tM2e chimeric VLPs as universal vaccines and warrant further investigation.

Predictors of Shingles Reports at Diagnosis of Common Variable Immunodeficiency and Selective Immunoglobulin G Subclass Deficiency in 212 Alabama Adults

We sought to determine predictors of shingles reports in adults with common variable immunodeficiency or immunoglobulin (Ig) G subclass deficiency (CVID/IgGSD). We tabulated observations at diagnosis of CVID/IgGSD in 212 white adult index patients (165 women, 47 men) who responded to a question about having had shingles. None had been vaccinated for herpes zoster. We analyzed age, sex, and shingles reports; blood levels of CD19+, CD4+, CD8+, and CD56+ mononuclear cells; serum levels of IgG subclasses, IgA, and IgM; and positivity for human leukocyte antigen (HLA)-A and -B haplotypes. Cell counts and immunoglobulin levels were normalized with loge (ln) transformation for analyses. Thirty-one patients (14.6%) reported shingles; 11 reported recurrent or disseminated shingles. Patients with shingles reports had greater mean age at diagnosis of CVID/IgGSD [54±13 (standard deviation) years vs. 47±12 years; P=0.0130] and a greater prevalence of HLA-A*01, B*08 positivity (35.5% vs. 17.7%; P=0.0227). In a 13-factor logistic regression model, there was a positive association of age with shingles reports [P=0.0151; odds ratio (1.05, 95% confidence interval 1.01, 1.08)]. HLA-A*01, B*08 positivity was also positively associated with shingles reports [P=0.0480; odds ratio 2.61 (1.00, 6.81)]. During a mean followup interval of 7.5 years after CVID/IgGSD diagnosis, the prevalence of recurrent shingles was almost five-fold greater in patients with previous shingles reports. In conclusion, in white adults at CVID/IgGSD diagnosis, age at diagnosis and positivity for HLA-A*01, B*08 have significant positive associations with reports of previous shingles.

IgG4 immune response in Churg–Strauss syndrome

ObjectiveT-helper type 2 responses are crucial in Churg–Strauss syndrome (CSS) and may enhance the production of IgG4 antibodies. The authors assessed the IgG4 immune response in CSS patients.MethodsThe authors included...