Dwindled serum IgG levels of Rubella, Diphtheria toxin, Hepatitis B virus and Tetanus Toxoid after chemotherapy; a report from Iranian children with malignancy

Backgrounds: Epigenetic regulation such as DNA methylation plays a major role in chromatin organization Background: Chemotherapy suppresses immunoglobulin production as a result of cell toxicity. Decreased immunoglobulin levels can result in the onset of opportunistic infections. The aim of the current study is to compare the immunoglobulin G (IgG) levels of the selected vaccine-preventable disease (VPD) before and six months after chemotherapy in a group of Iranian children with malignancies. Materials and Methods: In this interventional study, serum levels of Rubella, Diphtheria toxin, Hepatitis B virus (HBV), Tetanus Toxoid, Mumps, and Measles IgG were measured in 30 children with malignancy and previously vaccinated for these diseases. Six months after chemotherapy, serum IgG levels were reassessed and compared with their corresponding pre-chemotherapy levels. Results: In this study, 17 (56.7%) male and 13 (43.3%) female were included. The mean age was 7.69±3.09 years. After chemotherapy, Rubella IgG levels dropped from 73.88±85.11 to 56.59±72.84 IU/mL (P<0.05; r= 0.956; 33.4% become serum negative (SN)). Diphtheria toxin IgG was diminished from 0.683±0.454 to 0.174±0.248 IU/mL (P<0.05; r=0.601; 26.7% SN). Anti-HBV IgG showed a reduction from 46.26±101.56 to 25.56±80.49 IU/mL (p<0.05; r= 0.524; 60% SN) and Anti-Tetanus Toxoid IgG fell down from 1.031±0.582 to 0.321±0.408 IU/mL (p<0.05; r= 0.365; 33.4% SN). Anti-Measles and Anti-Mumps IgGs showed no significant change (p>0.05). Conclusion: Pediatric chemotherapy was associated with dropped serum IgG levels of most VPDs. A good correlation was also observed between serum levels of IgG before and six months after chemotherapy. Revaccination of children with malignancies may be necessary upon declined serum IgG titers.

Immunogenicity of BNT162b2 mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis on TNF inhibitors

BackgroundScanty data on the immunogenicity of the BNT162b2 vaccine in patients with psoriatic arthritis (PsA) on Tumor Necrosis Factor inhibitors (TNFi) have been published.ObjectiveTo investigate the humoral response to BNT162b2 vaccination patients with PsA on TNFi, comparing immunogenicity with healthy controls.MethodsForty patients with classified PsA on TNFi undergoing vaccination with the BNT162b2 mRNA SARS-CoV-2 vaccine (BioNTech/Pfizer) were enrolled. Fifteen days after the second shot, serum IgG levels against SARS-CoV-2 (Abbott ARCHITECT i2000SR, positivity cut-off 50 AU/mL) were assayed in all patients. Clinimetrics and treatment data were gathered. TNFi treatment was not discontinued throughout the whole period, whereas methotrexate (MTX) was discontinued for 1 week after each shot in those on combination therapy. Sera from healthcare professionals were considered as healthy controls for 1:1 propensity score matching; any of them was taking medication.Student’s t-test and logistic regression were used for investigating differences in immunogenicity between groups and predictors of antibody response.ResultsClinical Disease Activity Index did not change before and after vaccination (7.06±5.23 to 7.10±5.27, p=0.92).Patients with PsA achieved a positive anti-SARS-CoV-2 IgG level with a mean (±SD) of 13794.44±15 815.42 AU/mL. Although lower, the antibody level was not significantly different from matched controls (19227.4±11.8460.45 AU/mL, p=0.08). In the overall sample, those on MTX (12/80, 15%) had a trend toward lower immune response (p=0.07); glucocorticoid therapy (11/80, 13.8%) predicted lower antibody levels (p=0.04).ConclusionsContinuing TNFi in patients with PsA throughout the vaccination did not hamper immunogenicity.

Measurement of antibody levels in patients with COVID-19 over time by immunofluorescence assay: a longitudinal observational study

Background During the coronavirus disease 2019 (COVID-19) pandemic, antibody screening is a critical tool to assess anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity. We examined variation in antibody titers associated with age and sex among patients with confirmed COVID-19. Methods Blood IgG levels were tested in 1081 patients with positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests between 1 September and 31 December 2020. Patients who did not experience reinfection were identified. Serum IgG levels were measured by immunofluorescence assay. Antibody positivity and antibody titers were analyzed according to time since infection, sex, and age. Results The mean (standard deviation) age was 41.2 (14.2) years and 41.2% of patients were women. The lowest antibody positivity rate between the first and ninth month post-infection was detected in the sixth month. The lowest antibody titers among patients aged 20 to 80 years occurred in those aged 30 to 39 years. The IgG titer was positively correlated with age in years (r = 0.125) and decades (r = 0.126). Conclusions Six months after infection, anti-SARS-CoV-2 antibody titers increased. Anti-SARS-CoV-2 antibody titers also increased with age. Immunity and pathogenicity should be investigated in addition to antibody positivity rates and antibody titers.

Antibodies specific to SARS-CoV-2 proteins N, S and E in COVID-19 patients in the normal population and in historical samples

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally; recognition of immune responses to this virus will be crucial for coronavirus disease 2019 (COVID-19) control, prevention and treatment. We comprehensively analysed IgG and IgA antibody responses to the SARS-CoV-2 nucleocapsid protein (N), spike protein domain 1 (S1) and envelope protein (E) in: SARS-CoV-2-infected patient, healthy, historical and pre-epidemic samples, including patients’ medical, epidemiological and diagnostic data, virus-neutralizing capability and kinetics. N-specific IgG and IgA are the most reliable diagnostic targets for infection. Serum IgG levels correlate to IgA levels. Half a year after infection, anti-N and anti-S1 IgG decreased, but sera preserved virus-inhibitory potency; thus, testing for IgG may underestimate the protective potential of antibodies. Historical and pre-epidemic sera did not inhibit SARS-CoV-2, thus its circulation before the pandemic and a protective role from antibodies pre-induced by other coronaviruses cannot be confirmed by this study

Evaluation of B-Cell Kinetics After Acellular Pertussis Vaccination in Four Cohorts of Different Age and Priming Background

Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole cell to acellular pertussis vaccines, although other factors may also contribute. To develop future vaccines and improve current vaccination strategies, it is critical to understand factors influencing the generation of immunological memory. We applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. These findings were correlated to vaccine-specific plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days post-vaccination was the most prominent cellular change in all age groups, and was most pronounced for more mature IgG1+ plasma cells. Cellular responses were stronger in individuals primed with whole cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ plasma cell expansion weakly correlated with Prn- and PT- specific serum IgG levels. Our study points at plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and priming backgrounds.

Novel LysM motifs for antigen display on lactobacilli for mucosal immunization

We characterized two LysM domains of Limosilactobacillus fermentum, belonging to proteins Acglu (GenBank: KPH22907.1) and Pgb (GenBank: KPH22047.1) and bacterium like particles (BLP) derived from the immunomodulatory strain Lacticaseibacillus rhamnosus IBL027 (BLPs027) as an antigen display platform. The fluorescence protein Venus fused to the novel LysM domains could bind to the peptidoglycan shell of lactobacilli and resisted harsh conditions such as high NaCl and urea concentrations. Acglu with five LysM domains was a better anchor than Pgb baring only one domain. Six-week-old BALB/c mice were nasally immunized with the complex Venus-Acglu-BLPs027 at days 0, 14 and 28. The levels of specific serum IgG, IgG1 and IgG2a and the levels of total immunoglobulins (IgT) and IgA in broncho-alveolar lavage (BAL) were evaluated ten days after the last boosting. Venus-Acglu-BLPs027, nasally administered, significantly increased specific BAL IgT and IgA, and serum IgG levels. In addition, spleen cells of mice immunized with Venus-Acglu-BLPs027 secreted TNF-α, IFN-γ and IL-4 when stimulated ex vivo in a dose-dependent manner. We constructed a Gateway compatible destination vector to easily fuse the selected LysM domain to proteins of interest for antigen display to develop mucosal subunit vaccines.

No Obvious Role for Suspicious Oral Pathogens in Arthritis Development

A particular role for Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) has been suggested in periodontitis and rheumatoid arthritis (RA), as these bacteria could initiate the formation of rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPA). We assessed whether serum antibodies against Pg and Aa in RA patients and non-RA controls reflect the subgingival presence of Pg and Aa, and evaluated the relationship of these antibodies to the severity of periodontal inflammation and RA-specific serum autoantibodies. In 70 Indonesian RA patients and 70 non-RA controls, the subgingival presence of Pg and Aa was assessed by bacterial 16S rRNA gene sequencing, and serum IgG levels specific for Pg and Aa were determined. In parallel, serum levels of ACPA (ACPA:IgG,IgA) and RF (RF:IgM,IgA) were measured. The extent of periodontal inflammation was assessed by the periodontal inflamed surface area. In both RA patients and the controls, the presence of subgingival Pg and Aa was comparable, anti-Pg and anti-Aa antibody levels were associated with the subgingival presence of Pg and Aa, and anti-Pg did not correlate with ACPA or RF levels. The subgingival Pg and Aa were not related to RA. No noteworthy correlation was detected between the antibodies against Pg and Aa, and RA-specific autoantibodies.

Serum Protein Electrophoresis May Be Used as a Screening Tool for Antibody Deficiency in Children and Adolescents

BackgroundPatients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs.ObjectiveThis study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo).MethodsWe analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels.ResultsSerum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-&lt;18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels.ConclusionBoth CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.

Paratesticular fibrous pseudotumour: case report of a rare manifestation of IgG4-related disease

Background Paratesticular fibrous pseudotumour is a rare benign growth with unclear pathogenesis and clinical management. It has been linked to Serum IgG4-related disease. This mass can notoriously masquerade around as a malignancy; however, a conservative (testis sparing) approach is sufficient as surgical management. Case presentation We present the case of a 35-year-old gentleman who presented with a slow growing paratesticular mass, raising the suspicion of a malignancy. However, normal tumour markers and benign appearance on imaging modalities compelled us to give trial of local excision with intra-operative frozen section analysis. After confirmation of benign pathology of the mass, the incision was closed. Final histopathology confirmed the diagnosis of benign paratesticular fibrous pseudotumour, and serum IgG levels were noted to be elevated. Conclusion Thus, using tumour markers, radiological imaging and intraoperative frozen section, a potential radical resection can be avoided, testis sparing surgery, employed.

Serum IgG level is a predicting factor for the response to neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma

Background Despite the established oncological benefits of neoadjuvant chemotherapy for esophageal squamous cell cancer, not all cases demonstrate benefit. Hence, predicting the response to chemotherapy before treatment is desirable. Some reports have shown that immune factors are related to the chemotherapy response. This study aimed to investigate the utility of serum IgG levels for predicting chemotherapy response. Methods Among the patients who underwent esophagectomy after neoadjuvant chemotherapy at Nagoya City University Hospital between December 2012 and June 2019, 130 cases were included in this study. Response to chemotherapy and pretreatment serum IgG levels were examined in 77 cases. FP (5-fluorouracil and cisplatin) therapy or DCF (docetaxel, cisplatin, and 5-FU) therapy was performed as neoadjuvant chemotherapy. DCF therapy was selected for patients aged <75 years, who could be safely administered chemotherapy based on their medical history. Results This study divided cases into two groups: the effective response group (PR) and ineffective response group (SD and PD). We classified 1, 37, and 39 cases as PD, PR, and SD, respectively. None of the cases were classified as CR. The effective response group had significantly lower serum IgG levels than the ineffective response group (p < 0.001). The cutoff serum IgG value was determined to be 1087 mg/dL. The low IgG group had significantly more cases who had effective response to chemotherapy compared with the high IgG group (odds ratio [OR] = 9.009; 95% confidence interval [CI] = 2.974–30.157; p < 0.001). Univariate and multivariate analyses revealed serum IgG level to be an independent predictor for response to chemotherapy (p = 0.001). Furthermore, cases with effective pathological response had significantly lower pretreatment serum IgG levels than those who did not (p = 0.006). Conclusions Our finding showed that serum IgG levels can be an independent predictor of the response to neoadjuvant chemotherapy for esophageal squamous cell carcinoma. Trial registration This retrospective study was approved by the review board of Nagoya City University Graduate School of Medical Sciences (reception number: 60-18-0008).