IgG Levels Research Articles

Persistently Low IgG2 Levels in a Subset of Patients Following Hematopoietic Cell Transplantation.

Infectious diseases remain a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Secondary hypogammaglobulinemia is a risk factor for infectious diseases. Total immunoglobulin G (IgG) levels and the history of infectious diseases are an integral part of determining the indication for immunoglobulin replacement therapy. The clinical significance of IgG2 levels is not well established. Guidelines recommend using pathogen-specific IgG to evaluate patients with potential secondary immunodeficiency. However, it is difficult in practice to perform such testing. IgG2 may correlate well with pathogen-specific IgG but the clinical significance of IgG2 is not well established. To assess the prevalence of low IgG2 levels with normal IgG after HCT, we cross-sectionally measured the levels of several immunoglobulins, including IgG, IgA, IgM, and IgG2, after HCT, and we assessed the correlation between them. Among 121 patients who underwent cross-sectional measurements of IgG, IgA, IgM, and IgG2 levels after HCT, 114 had normal IgG2 levels (normal IgG2 group, ≥ 100mg/dL) and 7 had low IgG2 levels (low IgG2 group, < 100mg/dL). These 7 patients were allogeneic HCT recipients. All 7 patients with low IgG2 had cGVHD and 4/7 patients had normal total IgG levels. IgG2 levels may be low even in patients with normal IgG levels years after allogeneic HCT. Therefore, our study suggests that when patients develop infectious diseases, especially multiple episodes, it is recommended to measure IgG2 levels to exclude the possibility of secondary hypogammaglobulinemia after allogeneic HCT.

Impacts of ectoparasite flea infestation on gut microbiota of the Meriones unguiculatus in a rodent-flea system.

Fleas, along with one of their host species, Meriones unguiculatus, possess the capability to act as vectors in the transmission of plague. Parasitism by fleas may markedly influence the physiology and immune system of their hosts. Gut microbiota plays an important role in the growth and development of rodents. However, few studies have explored the impacts of ectoparasitic flea on the gut microbiome of rodents. This study investigated the immunological responses and changes in the gut microbial diversity and composition in both wild and laboratory rodents infested with fleas and laboratory rodents infested with Ctenocephalides felis. We measured immune reactions post-infestation by enzyme-linked immunosorbent assay (ELISA) and explored the effects of ectoparasitic infestation on the diversity and composition of the rodent gut microbiota in microbiome studies by 16S rRNA gene sequencing techniques. After flea infestation, results from 16S rRNA gene sequencing techniques indicated a significant increase in alpha diversity, affecting the composition of the gut microbiota. At the genus level, the abundance of the harmful bacterium Desulfovibrio increased. Beta diversity analyses showed significant differences between the gut microbiota of the experimental and control groups. ELISA results revealed significantly elevated levels of IgG in parasitized mice, while the differences in IgA levels were not significant. Flea infections affect the composition and diversity of the gut microbiota in the M. unguiculatu, and it has been found that the biomarker Desulfovibrio increases following flea infection in these rodents. Our results indicate that the gut microbiota can regulate the stability of the rodent-flea system. These findings may provide a foundation for exploring preventive measures against plague and aid in developing more effective treatments for the infection.

Features of the immune system and levels of blood transport components in residents of the arctic of the Russian Federation.

The peripheral venous blood of 191 residents of the Arctic of the Russian Federation (Murmansk Oblast) aged 21-55 analyzed comprehensively. Blood was sampled from the ulnar vein on an empty stomach in the morning. The hemogram, phagocytic activity of neutrophils, lymphocyte content with CD3, CD4, CD8, CD10, CD19, CD16, CD71, CD25, HLA-DR and CD95 phenotypes, concentrations of cytokines: TNF-α, IFN-γ, IL-6, IL-10, extracellular receptor pool: sCD71, sCD62L, sApo-1/Fas, sFasL, circulating immune complexes (CIC) and blood transport components: haptoglobin (Hp), transferrin, IgM, IgG, IgA, IgE (immunoglobulins M, G, A and E) low-density lipoproteins (LDL), and high density lipoprotein (HDL) were evaluated. The results were analyzed using descriptive statistics and comparative, factorial, and regression analyses. Residents of the Murmansk Oblast exhibit a high prevalence of erythrocytosis (62.3%), thrombocytosis (25.0%), leukocytosis (20.1%), and increased hemoglobin (Hb) concentrations (42.5%), coupled with a significantly decreased level of active phagocytes (47.6%). A significantly decreased level of lymphocytes with phenotypes CD3 (92.4%), CD4 (40.4%), CD71 (62.3%) was revealed, coupled with the activation of lymphocytes with phenotypes CD16 (50.1%), CD8 (37.5%), CD19 (15.9%) and increased concentrations of pro-inflammatory IFN-γ (47.9%), IL-6 (33.3%), and TNF-α (20.1%). Elevated levels of sCD71 (56.6%), sCD62L (32.1%), sApo-1/Fas (22.1%), sFasL (10.2%), and autoantibodies to double-stranded DNA (57.1%), RNA (10.4%), and oLDL (oxidized-modified LDL) (16.3%) were recorded in residents of the Murmansk Oblast. Arctic residents showed elevated concentrations of Hp (63.3%), IgM (63.9%), IgA (42.4%), IgE (18.8%), LDL (24.9%), and a decreased level of HDL (21.1%) owing to an ApoA-I ligand deficiency (58.1%). Elevated levels of Hp in the blood are associated with increased erythrocyte aggregation frequency, T-lymphocyte activation, and increased concentration of free receptors of the extracellular pool. Increased IgM and IgA levels in the blood are attributed to the need to bind components of the extracellular receptor pool sCD71, sCD62L, sApo-1/Fas, sFasL and are associated with decreased levels lymphocyte with CD8 and CD16 phenotypes. The humoral immune response in Arctic residents is triggered when the cellular component of immunity is under strain which compounded by ineffective clearance of metabolic byproducts owing to imbalanced LDL and HDL lipid transport complexes. The immune system of Arctic residents is characterized by excessive cytotoxic activity of lymphocytes and increased concentrations of pro-inflammatory cytokines, free forms of receptors of the extracellular pool, and autoantibodies. The change in the content of transport components of the blood system is directed at maintaining homeostasis by exhibiting antioxidant, anti-inflammatory, and immunoregulatory properties.

Development of bovine IgG3-specific assays using a novel recombinant single-domain binding reagent

Cattle express three subclasses of IgG antibody - IgG1, IgG2 and IgG3. Unlike IgG1 and IgG2, IgG3 was described relatively recently and the role of this subclass in immunity is unknown. Using recombinant bovine IgG1, IgG2 and IgG3 monoclonal antibodies (mAbs), we demonstrated that only one of the commercially available anti-bovine IgG mAbs tested was able to recognize IgG3, and no mAb exclusively bound IgG3. Here, we evaluated a small ankyrin repeat protein, called Ankyron™ AZS40101, that was generated to bind to bovine IgG3. Ankyron™ AZS40101 bound specifically to IgG3 with minimal reactivity to IgG1 and IgG2. Ankyron™ AZS40101 was shown to be useful in ELISA assays as either a capture or detection reagent. Utilisation of Ankyron™ AZS40101 alongside IgG1 and IgG2 specific mAbs to detect antigen-specific IgG subclasses in the serum of cattle sequentially vaccinated with heterologous foot-and-mouth disease virus capsid antigens revealed a low-level antigen-specific IgG3 response, in addition to IgG1 and IgG2 responses. Assessment of the total IgG1, IgG2 and IgG3 levels in healthy cattle plasma samples showed that IgG3 was measurable at a mean concentration of 0.19mg/mL, although this was significantly lower than those of IgG1 (mean 3.28mg/mL) and IgG2 (mean 3.41mg/mL). Thus, Ankyron™ AZS40101 is a new reagent that provides utility for measurement of bovine IgG3 responses to infection and vaccination.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral delivery system for H9N2 vaccine to promote systemic and mucosal immune response.

Most infectious diseases are caused by pathogens that invade the body tissues through mucosal tract. Therefore, it is essential to develop effective vaccines administered through the mucosa as a first-line of defense against major infectious diseases. Oral delivery of vaccines is currently of great interest due to its potential to elicit both mucosal and systemic immune responses, high compliance rate and non-invasive nature. However, their development is limited by the challenging gastrointestinal (GI) environment, the low permeability of the mucus barrier, and the lack of effective and safe mucosal adjuvants. Currently, nanoparticle-based strategies show significant potential for improving oral vaccine delivery systems. Herein, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were developed for oral delivery of H9N2 antigen. CDP-DFNS induced the activation of macrophages, thereby enhancing antigen uptake in vitro. Additionally, CDP-DFNS/H9N2 significantly activated the dendritic cells (DCs) in Peyer's patches (PPs), and T/B cells in mesenteric lymph nodes (MLNs). Moreover, CDP-DFNS/H9N2 enhanced the HI titers and levels of H9N2-specific antibody IgG, secretory IgA (SIgA) and H9N2-specific IgA in intestinal and respiratory mucosa, as well as Th-associated cytokines. Our results indicate that CDP-DFNS could be a promising oral vaccine adjuvant delivery system.

Unravelling the role of secretory Immnuoglobulin-A in COVID-19: a multicentre study in nursing homes during the first wave

BackgroundThe function of mucosal secretory IgA (SIgA) seems to be paramount in the immune response against SARS-CoV-2 however, there are few studies addressing this issue specifically in the institutionalized older population. This study aims to determine the levels of secretory IgA against the S1 domain of the SARS-CoV-2 spike (SIgA-S1) in older people living in nursing homes (NH) and to investigate the differences in baseline characteristics, severity of COVID-19, duration of symptoms, 30-day mortality, and reinfection according to the levels of SIgA-S1.MethodsIn this multicentre longitudinal study, conducted in two NHs attended in coordination with a hospital-based Geriatric team, 305 residents (87.3 years, 74.4% female) were included. A massive collection of nasopharyngeal samples was carried out after the first wave of COVID-19 in May 2020 and an ELISA analysis of SIgA-S1 was performed on frozen samples in May 2023. Values of SIgA-S1 ≥ 57.6 U/mL (“cut-off point”) were considered “induced”. Resident medical records were reviewed to assess symptoms, comprehensive geriatric assessment (CGA), reinfection, and overall 30-day mortality.ResultsAt the time of sample collection, 274 residents (89.8%) exhibited “induced” SIgA-S1 levels (≥ 57.6 U/mL), 46 (15.1%) tested positive for PCR SARS-CoV-2, and 170 (57%) had experienced COVID-19 symptoms. “Induced” SIgA-S1 patients were more likely to be symptomatic (60.3% vs. 29%; p < 0.001) and exhibited upper respiratory tract symptoms more frequently (25.1% vs. 6.5%; p = 0.020) compared to “non-induced” patients. Patients with severe disease and duration of symptoms > 10 days had higher levels of SIgA-S1 than those with mild disease (252 vs.192.6 U/mL; p = 0.012) or duration ≤ 10 days (270.5 vs. 208.1 U/mL; p = 0.043), respectively. No significant differences were observed in age, sex, CGA, duration of symptoms, disease severity, overall 30-day-mortality, or reinfection between “induced” and “non-induced” residents.ConclusionsLevels of SIgA-S1 are associated with the duration and type of COVID-19 symptoms, along with the severity of infection. While these findings shed light on the knowledge of SIgA-S1, further interdisciplinary studies are warranted to better understand the immune response to SARS-CoV-2 infection.

A Dual-Adjuvanted Parenteral-Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS-CoV-2 in Mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual-adjuvanted (RIG-I: PUUC RNA and TLR-9: CpG DNA) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) along with SARS-CoV-2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

Hemophagocytic Lymphohistiocytosis: Clinical Characteristics and Diagnostic Prediction Model

To investigate the clinical characteristics of patients with hemophagocytic lymphohistiocytosis (HLH) and quantify the diagnostic value of various indexes in patients with elevated soluble interleukin-2 receptor (sCD25), so as to construct a diagnostic prediction model of HLH. The clinical characteristics of 121 patients with elevated sCD25 (≥2 400 U/ml) in the Third Affiliated Hospital of Sun Yat-Sen University were analyzed retrospectively. The patients were divided into HLH group and non-HLH group according to the diagnostic criteria of HLH. The patients with HLH were divided into infection group, tumor group, macrophage activation syndrome (MAS) group and unknown etiology group according to their etiology. The basic data and treatment of the patients were collected for univariate and multivariate logistic analysis to establish a diagnostic prediction model of HLH. Among the 121 enrolled patients with elevated sCD25, 68 were diagnosed as HLH. The proportion of patients using vasopressors, the incidence rate of disseminated intravascular coagulation (DIC), and the HScore in the HLH group were higher than those in the non-HLH group (P < 0.05). Hepatomegaly, splenomegaly, and hemophagocytosis were more common in HLH patients(P < 0.05). Compared with the patients in non-HLH group, patients in HLH group had lower levels of neutrophils, platelets, fibrinogen, IgG, and IgM, while the levels of triglycerides, ferritin (FER), sCD25, serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin (TBil), lactate dehydrogenase (LDH), and D-dimer were higher (P < 0.05). In subgroup analysis, the level of sCD25 in tumor group was higher than that in infection group. The level of sCD25/ferritin in tumor group was higher than that in infection group and MAS group. Compared with HLH patients in the tumor group, the procalcitonin (PCT) level, proportion of patients using vasopressors, positive rate of hemophagocytosis, and incidence rate of DIC were all higher in the infection group, and the differences were statistically significant (P < 0.05). The results of multivariate analysis showed that fever, splenomegaly, hemophagocytosis, cytopenias, IgM, M.sCD25 [multiple of sCD25 detection value relative to the diagnostic threshold (2400 U/ml)], fibrinogen, and triglycerides were independent predictive factors for HLH (P < 0.05).The diagnostic prediction model H constructed based on temperature, splenomegaly, hemophagocytosis, cytopenias, IgM, M.sCD25, fibrinogen, triglycerides showed good predictive accuracy. The optimal cutoff value of H was 39.45, the sensitivity of the model was 94.12%, the specificity was 83.02%. sCD25, sCD25/FER, PCT, hemophagocytosis, hemodynamic instability and DIC could help to distinguish the underlying etiology of HLH. The prediction model H has high discrimination and calibration, which could be used as a relatively accurate clinical diagnostic tool for HLH.

Neonatal SARS-CoV-2 mRNA Vaccination Efficacy Is Influenced by Maternal Antibodies.

Vaccination in pregnancy guards against infection. Maternal antibodies, however, can inhibit antibody production in neonates. We sought to determine the effects of maternal vaccination on neonatal immune response to a SARS-CoV-2 mRNA vaccine. We hypothesized that mRNA-lipid nanoparticles (LNP) vaccination allows for a de novo neonatal antibody response even in the presence of vertically transmitted maternal antibodies. Female mice were vaccinated with SARS-CoV-2 spike receptor binding domain (RBD) mRNA-LNPs. Mice were then bred, and 21-day-old pups were inoculated with the same mRNA-LNPs. Spike-specific IgG ELISAs were performed using mouse serum. A SARS-CoV-2 spike protein peptide library to perform peptide ELISAs characterized high affinity binding domains within the spike protein. Results were analyzed with one-way ANOVAs with Tukey's multiple comparisons tests. Compared to pups of unvaccinated dams, there were high levels of spike-specific IgG detected in the pups of vaccinated dams at 3 weeks of life (p < 0.0001). After neonatal vaccination, pups of unvaccinated dams had higher spike-specific serum IgG than pups of vaccinated dams at 12 weeks of life (p < 0.001). Antibody specificity to peptide moieties within spike RBD were similar when comparing a vaccinated dam to her pup at Week 3 of life, with different binding affinities observed in the pups by Week 15 of life. Pre-existing maternal antibodies may partially blunt the initial neonatal antibody response to mRNA-LNPs vaccination. This vaccine strategy, however, does not prohibit the subsequent development of a broad range of RBD antibody specificities that may be protective.

Altered B-cell, plasma cell and antibody immune profiles in blood of systemic mastocytosis

Systemic mastocytosis (SM) is a heterogeneous disease characterised by an expansion of KIT-mutated constitutively activated mast cells (MC) which release MC mediators that might act on the tumour microenvironment including other immune cells. Here we investigated the blood distribution of B-cell, plasma cell (PC) and antibody-isotype compartments in SM. We used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B-cells, PC and their subsets in blood of 108 SM patients - 35 bone marrow mastocytosis (BMM), 64 indolent SM (ISM), 9 aggressive SM (ASM)- vs 117 age-matched healthy donors (HD) and paired bone marrow (BM) samples of 31 SM vs 17 controls, respectively. In parallel, immunoglobulin (Ig) M, IgD, IgG, IgA and IgE plasma levels of were measured. Compared to HD, SM patients showed an increased immature B-cell production in BM (P=0.003) associated with a greater release of pre-germinal center immature (P<0.001) and naive CD5+ B-lymphocytes (P<0.001) to blood, but a pronounced decrease in PC counts of all different IgH-isotypes and subclasses (P≤0.001) together with overall increased IgM (P=0.001) and IgD (P<0.001) plasma levels. Of note, different immune profiles were found per diagnostic subtype of the disease with progressively greater counts in blood of immature B-lymphocytes together with decreased IgMD+, IgG2+, IgA1+ and IgA2+ MBC (P≤0.032) and elevated IgM (P=0.017) plasma levels in ASM cases, increased IgM (P=0.001) and IgD (P=0.001) plasma levels in ISM patients and exacerbated IgE (P<0.001) with decreased IgG (P=0.008) plasma levels in BMM cases. Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of SM patients, consistent with distinctly altered antibody-isotype profiles in plasma of BMM vs ISM vs ASM patients.

Anti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity. Four cohorts of pre-liver transplant PSC patients were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HC) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Olink® inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity. A total of 137 PSC patients (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD) and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HC) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared to PSC alone (p<0.0001 and 0.003) and HC (p<0.0001 and p<0.0001). However, anti-αvβ6 levels in PSC alone were not increased compared to HC. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity including alkaline phosphatase level (r=0.32, p=0.004), the revised Mayo PSC risk score (r=0.25, p=0.02) and liver stiffness measurement (r=0.43, p=0.008) after adjusting for age, gender, race/ethnicity and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling. Anti-αvβ6 autoantibodies identify a subset of PSC patients with concomitant IBD.

Nanospheres as the delivery vehicle: novel application of Toxoplasma gondii ribosomal protein S2 in PLGA and chitosan nanospheres against acute toxoplasmosis.

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.

B-cell and plasma cell activation in a mouse model of chronic muscle pain

Fibromyalgia (FM) is a complex chronic musculoskeletal pain disorder with an elusive pathogenesis, with a strong implication of immune interactions. We recently found that IL-5 and the adaptive immune system mediates pain outcomes in fibromyalgia (FM) patients and preclinical models of FM-like chronic widespread pain (CWP). However, there is an active debate if FM/CWP has an autoimmune etiology. Preclinical models of CWP utilize a repeated insult paradigm, which resembles a primary, then secondary response similarly observed in the antibody response in which the subsequent event causes a potentiated pain response. Recent translational studies have implicated immunoglobulins (Ig) and B-cells in FM/CWP pathophysiology. To understand if these are involved in preclinical models of CWP, we performed comprehensive B-cell phenotyping in the bone marrow, circulation, and popliteal (draining) lymph nodes in the two-hit acidic saline model of CWP. We found increased MHC class II-expressing B-cells in peripheral blood, increased activated plasma cells in peripheral blood, and increased memory B-cells in the bone marrow. Interestingly, acidic pH (4.0) injected mice have reduced levels of IgG1, independent of treatment with IL-5. We have demonstrated that the acidic saline model of CWP induces T-cell mediated activation of B-cells, increased active plasma cells, and increased memory B-cells in female mice.

Combination of Acanthocyturia and Elevated Serum IgA Level for the Diagnosis of IgA Nephropathy

Combination of Acanthocyturia and Elevated Serum IgA Level for the Diagnosis of IgA Nephropathy

Influence of Hematocrit and Storage Temperature on the Stability of Dried Blood Samples in Serological Analyses of Tetanus, Diphtheria, and Pertussis.

Dried blood spots (DBSs) enable the study of serological markers of various pathogens without the need to obtain serum/plasma through venipuncture. Sixty-four blood samples were prepared on Whatman™ 903 cards using specimens obtained by venipuncture to study the detection of serological markers of diphtheria, tetanus, and pertussis in DBSs, and their stability 4 months post-collection. An automated chemiluminescent immunoassay was used to investigate diphtheria, tetanus, and pertussis IgG levels from both DBSs and plasma samples. An optimal cut-off value for DBSs was calculated to improve the performance of diphtheria and tetanus serological markers in DBSs, achieving high sensitivity (95% and 98%, respectively) and specificity (91.7% and 92.3%, respectively). No protection against pertussis was found in the population studied. The correlation observed between the plasma and the DBSs processed after sample collection was high (0.967-0.970) for all antibodies studied except pertussis (0.753), both considering hematocrit before sample elution or not. The correlation between DBSs and plasma for diphtheria and tetanus remained strong following a 4-month delay in DBS processing at 4 °C (0.925-0.964) and -20 °C (0.924-0.966), with only a minor decrease observed for diphtheria at room temperature (0.889), while maintaining a strong correlation for tetanus (0.960). For pertussis, the correlation between DBSs and plasma was drastically reduced after delaying its processing for 4 months at any temperature. To summarize, hematocrit levels within the normal range do not affect the processing of DBSs in the study of serological markers of diphtheria, tetanus, and pertussis. The DBS stability for serological diagnosis of diphtheria and tetanus is adequate when samples are stored at -20 °C for a period of 4 months. The pertussis serological marker does not appear to remain stable after 4 months, even when the DBS is stored frozen at -20 °C.

Seroprevalence of antibodies against diphtheria, tetanus, and pertussis across various age groups during the post-COVID-19 pandemic period in Chonburi Province, Thailand.

BackgroundLimited data exists regarding population immunity against diphtheria, tetanus, and pertussis in Thailand during the post-COVID-19 pandemic period. This study aimed to evaluate the age-specific seroprevalence of anti-diphtheria toxoid (anti-DT) IgG, anti-tetanus toxoid (anti-TT) IgG, and anti-pertussis toxin (anti-PT) IgG in individuals across diverse age groups in Chonburi province, Thailand following the COVID-19 pandemic. MethodsBetween October 2022 and January 2023, a total of 657 participants from Chonburi Province, Thailand, were included in this study. The participants were categorized into 9 age groups: < 5, 5-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, and > 70 years. Analysis of anti-DT, anti-TT, and anti-PT IgG levels was conducted using commercial ELISA kits (EUROIMMUN, Lübeck, Germany). ResultsOverall, 65.4% of the population had seroprotection against diphtheria (antibody level ≥0.1 IU/mL), while 95.1% had seroprotection against tetanus (antibody level ≥0.1 IU/mL). The 31-40 years age group exhibited the lowest seroprotection for diphtheria (48.9%), and the > 70 years age group had the lowest seroprotection for tetanus (73.3%). The < 5 years age group showed the highest seropositive rate and highest geometric mean titers for anti-PT IgG. On the contrary, the majority of individuals over 11 years of age displayed anti-PT IgG levels below 40 IU/mL. ConclusionsTo prevent diphtheria and pertussis outbreaks in Chonburi province, implementing catch-up vaccination is necessary. Targeted interventions should be deployed to enhance vaccination coverage among the susceptible population.

Stability of SARS-CoV-2 antibody in serum under various usage and storage conditions.

We investigated the effect of two preanalytical variables, temperature change and freezing-thawing of serum samples, on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG levels. Serum samples were collected from patients who had coronavirus disease 2019 (COVID-19) prior to vaccination. Six serum samples were included, two each with high positivity (HP), low positivity (LP), and a level of close-to-detection limit (CDL) for SARS-CoV-2 IgG. Each of these six samples was divided into three tubes and placed in refrigerators at 4-8 °C, -20 °C, and -70 °C; removed from the storage temperature once per day for 20 consecutive days; and assayed for SARS-CoV-2 IgG level. The coefficient of variation of all the remaining serum samples were within 95% except for CDL-1 serum at -70 °C, HP-2 serum at 4-8 °C, HP-2 serum at -20 °C, and HP-2 serum at -70 °C. The levels increased significantly when the temperature in the samples with CDL was reduced. The values in samples with LP at -20 °C and -70 °C were significantly higher than those at 4-8°C. In the case of samples with HP, the values of samples at -20 °C were higher than those in samples at 4-8 °C. There was no positive-negative change during any of the freeze-thaw cycles. Antibody value in the samples at 4-8 °C remained stable throughout the 20 freeze-thaw cycles. The antibody value of the samples at -20 °C and -70 °C tended to elevate.

Parathyroid Hormone and Osteocalcin as Criteria for Osteoporosis in Patients with Celiac Disease

Background: Osteoporosis is a disease that affects the entire skeletal system. It is characterized by the deterioration of the fine structural structure of the bone and the decline in bone mass, which ultimately leads to an increase in the bone's susceptibility to fracture. Celiac disease, often known as wheat allergy, is a single condition with numerous names. Celiac disease is a chronic autoimmune disorder that mostly affects the small intestine. It occurs when patients develop an intolerance to gluten, a protein found in foods including wheat, rye, and barley. Aim of the study: The objective of our study is to track the levels of osteocalcin and parathyroid hormone in the blood serum of patients diagnosed with celiac disease in Wasit Governorate, Iraq. We will be using Human Anti-Deamidated Gliadin Peptide IgG and IgA to diagnose celiac disease and evaluate the progress of bone health. Materials and methods: This study examined a total of 80 samples, consisting of 50 samples from individuals with celiac disease. The sample group included 19 males and 31 women. There are 30 control samples, with an equal number of samples for each sexes. Utilized an Enzyme-linked immunosorbent assay (ELISA) kit to quantify the levels of osteocalcin, parathyroid hormone, and Human Anti-Deamidated Gliadin Peptide IgG and IgA. Results: The study revealed that individuals with celiac disease had significantly higher levels of osteocalcin, parathyroid hormone, and Human Anti-Deamidated Gliadin Peptide IgG and IgA compared to the control group, with a statistical significance of p≤(0.05). Conclusion: The examined parameters serve as indicators of the development of health risks to the body and bone health in individuals with celiac disease.

Monitoring humoral responses against three SARS-CoV-2 vaccines in a university population from Chihuahua, Mexico.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has spread worldwide since 2019. Survey of the antibodies against SARS-CoV-2 is one of the most important measures of immunity since it can give an idea on the effectiveness of administered vaccines and the serologic status of individuals. We determined the concentrations of blood IgM and IgG against three SARS-CoV-2 proteins in vaccinated teachers and students among a university population from Chihuahua, Mexico. Humoral response surveillance against the 3C-like proteinase (3CLpro), nuclear protein (NP), and receptor binding domain (RBD) of SARS-CoV-2 was carried out. A total of 239 samples were analyzed: 67 from teachers who were vaccinated with CanSino and 172 from students (27.9% were vaccinated with AstraZeneca, 32.6% with Sinovac, 24.4% with Pfizer-BioNTech, 15.1% with other vaccines). Significant differences in the levels of IgG were observed between serum from individuals prior to vaccination (preimmunization serum) and from those that were vaccinated with CanSino. However, samples from asymptomatic individuals did not show differences between the preimmunization and post-immunization serum. The three vaccinated groups (AstraZeneca, Pfizer and Sinovac) did not show significant differences in anti-RBD IgG antibody titers compared to the positive control group, except for a Pfizer non-COVID-19 subgroup where the level of antibodies in the Pfizer group was 1.7 times higher. Neither vaccine group showed significant differences between those individuals who previously had COVID-19 and uninfected individuals. These results provide a picture of the situation at the time when in-person classes resumed.