Serum IgM Levels Research Articles

Oral immunizations with Bacillus subtilis spores displaying VP19 protein provide protection against Singapore grouper iridovirus (SGIV) infection in grouper.

Disease caused by Singapore grouper iridovirus (SGIV) results in major economic losses in the global grouper aquaculture industry. Vaccination is considered to be the most effective way to protect grouper from SGIV. In this study, the spores of Bacillus subtilis (B.subtilis) WB600 were utilized as the vehicle that the VP19 protein was displayed on the spores surface. To further investigate the effect of oral vaccination, the grouper were orally immunized with B.s-CotC-19 spores. After challenged, the survival rate of grouper orally vaccinated with B.s-CotC-19 spores was 34.5% and the relative percent survival (RPS) was 28.7% compared to the PBS group. Moreover, the viral load in the tissues of the B.s-CotC-19 group was significantly lower than that of the PBS group. The histopathological sections of head kidney and liver tissue from the B.s-CotC-19 group showed significantly less histopathology compared to the PBS group. In addition, the specific IgM levels in serum in the B.s-CotC-19 group was higher than those in the PBS group. In the hindgut tissue, the immune-related gene expression detected by quantitative real-time PCR (qRT-PCR) exhibited an increasing trend in different degrees in the B.s-CotC-19 group, suggesting that the innate and adaptive immune responses were activated. These results indicated that the oral administration of recombinant B.subtilis spores was effective for preventing SGIV infection. This study provided a feasible strategy for the controlling of fish virus diseases.

Sub-chronic exposure of Oreochromis niloticus to environmentally relevant concentrations of smaller microplastics: Accumulation and toxico-physiological responses

This study assesses the accumulation and toxic effects of environmentally relevant concentrations (0.01, 0.1 and 1 mg/L) of polystyrene MPs (1 µm) in Oreochromis niloticus (Nile tilapia) for 14 days. The results showed that 1 µm PS-MPs accumulated in the intestine, gills, liver, spleen, muscle, gonad and brain. RBC, Hb and HCT showed a significant decline, while WBC and PLT showed a significant increase after the exposure. Glucose, total protein, A/G ratio, SGOT, SGPT and ALP showed significant increments in 0.1 and 1 mg/L of PS-MPs treated groups. The increase in cortisol level and upregulation of HSP70 gene expression in response to MPs exposure indicate MPs-mediated stress in tilapia. MPs-induced oxidative stress is evident from reduced SOD activity, increased MDA levels and upregulated P53 gene expression. The immune response was enhanced by inducing respiratory burst activity, MPO activity and serum TNF-α and IgM levels. MPs exposure also led to down-regulation of CYP1A gene and decreased AChE activity, GNRH and vitellogenin levels, indicating the toxicity of MPs on the cellular detoxification mechanism, nervous and reproductive systems. The present study highlights the tissue accumulation of PS-MP and its effects on hematological, biochemical, immunological and physiological responses in tilapia with low environmentally relevant concentrations.

Anti- SARS-CoV-2 IgG and IgM Levels in Iraqi General Population.

Acquired immunity plays an important role in the prevention of viral infections. SARS-CoV-2 is an infection that leads to a pandemic. The development of specific anti-SARSCoV- 2 antibodies may play a vital role in disease prevention and control. Thus IgG antibody screening in the general population provides information on the immunological status of the community. To clarify the SARS-CoV-2 immune status in the general population. A cross-sectional study was conducted in Kirkuk province during the period from 15 May 2022 to 11 September 2022. The samples were collected from voluntary subjects and informed consent was taken from each participant before their enrolment in the study. SARS-CoV-2 IgG, SARSCoV- 2 IgM, 25-OH Vitamin D, Vitamin B12, and Folate were determined using the Electrochemiluminescence Immunoassay (eCLIA) technique with the instrument NIPIGON-Robot R1Automated ECL Analyzer (Canada). The overall IgG mean concentration was 37.75 ± 23.18 COI, with a median of 39.99 COI and a range of 0.25 - 87.23 COI. Additionally, 93% of tested samples were with concentrations of more than 1 COI. The highest frequency (18.2%) was for the IgG concentration of 51 to 60 COI, while the lowest frequency (1.3%) was for the concentration of 81 - 90 COI. The IgG was significantly higher (P = 0.046) in males (39.87 ± 24.04 COI) than that in females (35.12 ± 21.89 COI). The IgM overall concentration was 0.569 ± 0.456 COI, with a median of 0.489 COI and a range of 0.17 - 6.40 COI. The mean serum level of folic acid concentration was 9.03 ± 5.72 ng/ml, with a median of 7.476 ng/ml and a range of 0.60 - 20.00 ng/ml. The mean serum concentration of vitamin B12 was 462.65 ± 349.18 pg/ml, with a median of 353 pg/ml and a range of 13.05 - 2000 pg/ml. The mean serum concentration of vitamin D was 18.29 ± 18.42 ng/ml with a median of 12.44 ng/ml and a range of 3 - 100 ng/ml. IgG and IgM serum levels did not show a significant correlation with serum levels of folic acid, vitamin D, and vitamin B12. However, there was a significant correlation between folic acid and vitamin D (r = 0.197; P = 0.012); vitamin B12 and vitamin D (r = 0.253, P = 0.001). While there was a non-significant correlation between folic acid and vitamin D serum levels (r = 0.129, P = 0.10). General population IgG antibody concentration reflects a high rate of herd immunity. Folic acid was with a mean value of about half of the upper normal limit and only 17.7% were with low values. Vitamin B12, only 6.3% of the population had values lower than normal. However, the range of vitamin B12 was wide. While vitamin D values were lower than the normal limit at 82.6%. However, a large scale well designed was warranted to evaluate COVID-19 national immune response.

THE INCIDENCE, CLINICAL APPLICATION AND PROGNOSTIC SIGNIFICANCE OF MYD88 AND CXCR4 MUTATION IN CHINESE PATIENTS WITH LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTRöM MACROGLOBULINEMIA

Introduction: Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, B-cell lymphoma with highly prevalent somatic mutations including MYD88, and CXCR4. The mutation rates of LPL/WM in China and the direct comparison among different deletion means are still not clear. Methods: 387 patients with LPL/WM were included in this study. Tumor cells were collected from 357 un-sorted BM 28 PB and 2 lymph nodes (FFPE). MYD88L265P mutation were detected by Sanger sequencing (FGS), NGS, allele-specific quantitative polymerase chain reaction (ASPCR), and droplet digital polymerase chain reaction (ddPCR). CXCR4 mutation were detected by Sanger sequencing, NGS, and ASPCR. Results: 386 patients were assessed for MYD88L265P mutation, of whom 263 were tested by FGS, 235 by NGS, 311 for AS-PCR, 118 for ddPCR. The MYD88L265P mutation was found in 88.6% of the patients. ASPCR and ddPCR had the highest sensitivity of 97.1% and 96.8%. FGS and NGS failed to detected the mutation in low tumor load. A high false-negative rate (FNR) for MYD88 by FGS and NGS was observed in patients with tumor load less than 10% (FNR: 35.5% and 20%). There was no significant difference in the MYD88 mutation rate detected by ddPCR and ASPCR among patients with different tumor load groups (p = 0.794). MYD88 mutation was detected in a high incidence of 88.5% in less than 1% infiltrated WM tumor cells specimens by ddPCR and ASPCR. CXCR4 mutation testing was performed in 358 patients of LPL/WM, comprising 301 with FGS, 236 with NGS, and 311 with ASPCR. Overall, 31.2% patients were identified as having the CXCR4 mutation. NGS exhibited the highest sensitivity among the three detection means. MYD88 wild-type patients had a significantly lower Hb levels (median 79 g/L vs. 90 g/L, p = 0.015), lower proportion of males (54.5% vs. 51.8%, p = 0.012) and a significantly higher proportion elevated β2-MG (84.2% vs. 65.6%, p = 0.021), and LDH (30.2% vs. 11.9%, p = 0.001). However, there were no significant differences in either PFS or OS between MYD88L265P wild-type and MYD88L265P mutation group (p = 0.35, p = 0.42). Patients with CXCR4 mutation tended to be older (median 64 vs. 60, p < 0.001) and displayed lower hemoglobin level (median 81 g/L vs. 93 g/L, p = 0.008), higher serum IgM level (median 36.1 g/L vs. 31.6 g/L, p < 0.001), and higher baseline BM involvement (by FCM, median 15.1% vs. 7.1%, p < 0.001) compared with CXCR4 wild-type patients. Notably, CXCR4 mutation group had significantly worse survival compared with the wild-type group (p = 0.03, p = 0.02). The research was funded by: National Nature Science Foundation of China (81970187, 82170193, 81920108006, and 81900203) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2022-I2M-1-022, 2021-I2M-C&T-B-081) Keywords: diagnostic and prognostic biomarkers, indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Persistent SARS-CoV-2 PCR Positivity Despite Anti-viral Treatment in Immunodeficient Patients

PurposeCOVID-19 infection in immunodeficient individuals can result in chronically poor health, persistent or relapsing SARS-CoV-2 PCR positivity, and long-term infectious potential. While clinical trials have demonstrated promising outcomes using anti-SARS-CoV-2 medicines in immunocompetent hosts, their ability to achieve sustained viral clearance in immunodeficient patients remains unknown. We therefore aimed to study long-term virological outcomes in patients treated at our centre.MethodsWe followed up immunocompromised inpatients treated with casirivimab-imdevimab (Ronapreve) between September and December 2021, and immunocompromised patients who received sotrovimab, molnupiravir, nirmatrelvir/ritonavir (Paxlovid), or no treatment from December 2021 to March 2022. Nasopharyngeal swab and sputum samples were obtained either in hospital or in the community until sustained viral clearance, defined as 3 consecutive negative PCR samples, was achieved. Positive samples were sequenced and analysed for mutations of interest.ResultsWe observed sustained viral clearance in 71 of 103 patients, none of whom died. Of the 32/103 patients where sustained clearance was not confirmed, 6 died (between 2 and 34 days from treatment). Notably, we observed 25 cases of sputum positivity despite negative nasopharyngeal swab samples, as well as recurrence of SARS-CoV-2 positivity following a negative sample in 12 cases. Patients were then divided into those who cleared within 28 days and those with PCR positivity beyond 28 days. We noted lower B cell counts in the group with persistent PCR positivity (mean (SD) 0.06 (0.10) ×109/L vs 0.22 (0.28) ×109/L, p = 0.015) as well as lower IgA (median (IQR) 0.00 (0.00–0.15) g/L vs 0.40 (0.00–0.95) g/L, p = 0.001) and IgM (median (IQR) 0.05 (0.00–0.28) g/L vs 0.35 (0.10–1.10) g/L, p = 0.005). No differences were seen in CD4+ or CD8+ T cell counts. Antiviral treatment did not impact risk of persistent PCR positivity.ConclusionPersistent SARS-CoV-2 PCR positivity is common among immunodeficient individuals, especially those with antibody deficiencies, regardless of anti-viral treatment. Peripheral B cell count and serum IgA and IgM levels are predictors of viral persistence.

Multiple Intestinal Atresia with Combined Immunodeficiency, a New Gene Arises

We present here a single case report of a 2-day-old female born to a 29-year-old G4P3→4 Swartzentruber Amish mother at 35 weeks gestation that presented with abdominal distension and failure to pass meconium.Family history was positive for a cousin born with multiple intestinal atresia (MIA) and combined immunodeficiency (CID) who died in his first month of life. A primary immune deficiency targeted gene panel was done, covering TTC7A, in addition to 206 other genes, with no known mutations identified.An exploratory laparotomy was performed on DOL4 with MIA observed, as well as malrotation without volvulus. Repair of pyloric atresia and multiple small bowel resections and anastomosis were performed. She was kept NPO with TPN and NG suctioning of gastric contents for bowel rest.Immunologic profiling revealed low CD3+ cells (578/µL), very low CD8+ T cells (23/µL), low CD4+ T cells (485/µL), normal NK and B cell counts, low levels of serum IgM (< 10 mg/dL) with normal levels of IgG (likely maternal) and IgA. Mitogen stimulation testing was normal. Sanger sequencing showed a homozygous c.4867 T>G (p.Tyr1623Asp) mutation in PIK4A confirming the diagnosis of Gastrointestinal Defects and Immunodeficiency Syndrome 2 (GIDID2). Despite surgery, the patient continued to have large volume NG output without return of bowel function. Other treatment options, including long term TPN, potential small bowel and liver transplants, and HSCT were discussed, but the family elected for hospice given the poor prognosis. She passed away on DOL 28. PI4KIIIα, encoded by PI4KA, catalyzes the conversion of phosphatidyl inositol to phosphatidyl inositol-4-phosphate while using TTC7A as a scaffolding protein. This process is critical for development of enterocyte polarity and actomyosin contractility in multiple cell types. PI4KA mutations have only recently been implicated in causing MIA with CID and can be missed in many genetic screens. GIDID2 is a devastating disease in which intestinal surgery provides only an immediate mechanical fix, without improving mortality. Further research on the molecular mechanisms that govern GIDID2 is critically needed to identify new treatment modalities. Furthermore, awareness of PI4KA mutations in newborns with MIA with CID is critical, particularly in Amish populations.

Calculated Globulin Is Clinically Useful as a Screening Test for Antibody Deficiency in Turkish Adult Patients

Introduction: Heterogeneous clinical features of antibody deficiency (AD) may cause diagnostic delays. Calculated globulin (CG) (total protein minus albumin) has been proposed as a screening test to prevent morbidity due to diagnostic delays in AD. Our aim was to validate CG as a screening test for AD in Turkish adult patients by comparing its role with gamma globulin analysis in protein electrophoresis. Methods: Fifty serum samples were randomly collected for each level of CG from 15 to 25 g/L and tested for serum IgG, IgA, IgM levels and protein electrophoresis. Cut-off values predicting low IgG levels were calculated for electrophoretically determined gamma globulin and CG. Additionally, the data of 47 patients followed up in our clinic with a diagnosis of primary antibody deficiency (PAD) were retrospectively analyzed. Results: A total of 550 adult patients were included in the study. The CG value predicting patients with IgG <6 g/L as a screening test was determined as <20 g/L with 83.8% sensitivity and 74.9% specificity. The gamma globulin value which predicted patients with the same IgG value of 89.0% sensitivity and 89.4% specificity was determined as <7 g/L. In the retrospective analysis, 37 of 47 patients (78.7%) with PAD had a CG value of <20 g/L at the time of the diagnosis and all 13 patients (100%) whose gamma globulin values were measured at the time of the diagnosis had a gamma globulin value of <7 g/L. Conclusion: The determined CG cut-off value of <20 g/L can be used as a screening test in Turkish adult patients.

Five-Year Safety of Ofatumumab in People Living With Relapsing Multiple Sclerosis (P8-3.004)

Five-Year Safety of Ofatumumab in People Living With Relapsing Multiple Sclerosis (P8-3.004)

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors. A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303). Povetacicept was compared to wild-type (WT) TACI-Fc and related molecules in vitro and in vivo. Povetacicept inhibited APRIL and BAFF more effectively than all evaluated forms of WT TACI-Fc and selective APRIL and BAFF inhibitors in cell-based reporter assays and primary human B cell assays, mediating potent suppression of B cell proliferation, differentiation, and immunoglobulin (Ig) secretion. In mouse immunization models, povetacicept significantly reduced serum immunoglobulin titers and antibody-secreting cells more effectively than anti-CD20 monoclonal antibodies, WT TACI-Fc, or APRIL and BAFF inhibitors. In the NZB × NZW mouse lupus nephritis model, povetacicept significantly enhanced survival and suppressed proteinuria, anti-double-stranded DNA antibody titers, blood urea nitrogen, glomerulonephritis, and renal immunoglobulin deposition. In the bm12 mouse lupus model, povetacicept significantly reduced splenic plasmablasts, follicular helper T cells, and germinal center B cells. In non-human primates, povetacicept was well tolerated, exhibited high serum exposure, and significantly decreased serum IgM, IgA, and IgG levels after a single dose. Enhanced APRIL and BAFF inhibition by povetacicept led to greater inhibition of B cell populations critical for autoantibody production compared to WT TACI-Fc and CD20-, APRIL-, or BAFF-selective inhibitors. Potent, dual inhibition by povetacicept has the potential to significantly improve clinical outcomes in autoantibody-related autoimmune diseases.

Anti-CD20 antibodies and bendamustine attenuate humoral immunity to COVID-19 vaccination in patients with B-cell non-Hodgkin lymphoma

Serologic responses of COVID-19 vaccine are impaired in patients with B-cell lymphoma, especially those who had recently been treated with anti-CD20 monoclonal antibodies. However, it is still unclear whether those patients develop an immune response following vaccination. We investigated the efficacy of vaccination against SARS-CoV-2 in 171 patients with B-cell non-Hodgkin lymphoma (B-NHL) who received two doses of an mRNA-based COVID-19 vaccine and we compared the efficacy of vaccination to that in 166 healthy controls. Antibody titers were measured 3 months after administration of the second vaccine dose. Patients with B-NHL showed a significantly lower seroconversion rate and a lower median antibody titer than those in healthy controls. The antibody titers showed correlations with the period from the last anti-CD20 antibody treatment to vaccination, the period from the last bendamustine treatment to vaccination and serum IgM level. The serologic response rates and median antibody titers were significantly different between diffuse large B-cell lymphoma (DLBCL) patients in whom anti-CD20 antibody treatment was completed within 9 months before vaccination and follicular lymphoma (FL) patients in whom anti-CD20 antibody treatment was completed within 15 months before vaccination. Moreover, the serologic response rates and median antibody titers were significantly different among FL patients in whom bendamustine treatment was completed within 33 months before vaccination. We demonstrated that B-NHL patients who were recently treated with anti-CD20 antibodies and bendamustine had a diminished humoral response to COVID-19 vaccination. UMIN 000,045,267.

Characterization of lymphocyte subsets and intestinal short-chain fatty acids in benzene-induced immunosuppressive mice.

Exposure to benzene causes immunosuppression, but the mechanism has not been clarified. In this study, mice were subcutaneously injected with different concentrations (0, 6, 30 and 150 mg/kg) of benzene for four weeks. The lymphocytes of bone marrow (BM), spleen and peripheral blood (PB) and the level of short-chain fatty acids (SCFAs) in mouse intestine were measured. The results showed that benzene exposure led to a reduction in CD3+ and CD8+ lymphocytes in mouse BM, spleen and PB, and CD4+ lymphocytes were increased in mouse spleen but decreased in mouse BM and PB after 150 mg/kg benzene exposure. In addition, Pro-B lymphocytes were reduced in mouse BM in the 6 mg/kg group. Besides, the levels of IgA, IgG, IgM, IL-2, IL-4, IL-6, IL-17a, TNF-α and IFN-γ in mouse serum were reduced after benzene exposure. Furthermore, the levels of acetic, propionic, butyric and hexanoic acid were reduced in mouse intestine, and the AKT-mTOR signaling pathway was activated in mouse BM cells after benzene exposure. Our results demonstrate that benzene induced immunosuppression in mice, and the B lymphocytes in BM are more sensible to benzene-induced toxicity. The reduction in mouse intestinal SCFAs as well as the activation of AKT-mTOR signaling may be related to the occurrence of benzene immunosuppression. Our study provides new insight for further mechanistic research on benzene-induced immunotoxicity.

Fermented Bamboo Fiber Improves Productive Performance by Regulating Gut Microbiota and Inhibiting Chronic Inflammation of Sows and Piglets during Late Gestation and Lactation.

Sows exhibit metabolic syndrome and significant changes in intestinal microbiota during late gestation and lactation, affecting sow performance and piglet health. Dietary fiber (DF) is widely applied to improve sow performance by modulating gut microbiota and their by-products. Here, 60 sows were randomly allocated to groups, including CON (8% wheat bran), FBF-1 (1% fermented bamboo fiber), FBF-2 (2.5% fermented bamboo fiber), and FBF-3 (4% fermented bamboo fiber) from day 80 of gestation (G80d) to the end of lactation (L21d). Compared with CON, the FBF-3 diet decreased lactation backfat loss, increased average daily feed intake (ADFI) during lactation, and the weight gain of piglets, while supplementation of FBF increased fecal water content and reduced the rate of constipation in sows. Further, the yield and quality of milk of sows in FBF groups were improved. The FBF-3 diet significantly reduced markers of intestinal permeability (diamine oxidase and endotoxin) and systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha) in sow serum during lactation, while it increased the anti-inflammatory marker (IL-10). Similarly, the piglets in the FBF-2 and FBF-3 groups had lower levels of IL-6 and higher levels of IgG, IgM, and insulin-like growth factor in serum. In addition, sows fed the 4% FBF diet had higher levels of acetate, propionate, butyrate, and total short-chain fatty acids (SCFAs) in feces than CON, and total SCFAs were promoted in piglets from the FBF-3 group. Spearman correlation analysis showed that immunity, inflammation, and intestinal microbiota are closely related to sow performance, which can affect piglet growth. The potential mechanism could be that FBF promoted the enrichment of beneficial genera such as Lachnospira, Lachnospiracea_XPB1014_Group, and Roseburia and the production of SCFAs in the sow's intestine, and reduced the relative abundance of harmful bacteria such as Fusobacterium, Sutterellaceae, and Sutterella. Meanwhile, the intake of FBF by sows affected the gut microbial composition of their offspring piglets, significantly increasing the relative abundance of beneficial bacteria Alistipes and Lachnoclostridium and decreasing the relative abundance of pathogenic bacteria Trueperella among colonic microorganisms. IMPORTANCE Dietary fiber is widely applied in the nutrition of sows due to its potential value in improving performance and intestinal health. Fermented bamboo fiber, rich in dietary fiber, has not been fully evaluated to be used in sow diets. Sows mobilize body reserves during gestation and lactation due to nutrients being prioritized for lactation purposes while feeding piglets, which generally leads to metabolism and immunity undergoing drastic changes. The main manifestations are increased inflammation and intestinal permeability and disturbed intestinal flora, which ultimately reduces the ADFI and milk quality, thus affecting the growth of piglets. The study described here is the first attempt to provide FBF for sows in late gestation and lactation can reverse this process. The 4% FBF was initially explored to have the most significantly beneficial effect. It provides a potentially effective method for dietary modification to control the gut microbiota and its metabolites to improve sow and piglet health. Moreover, the sow-piglet model offers a reference for investigating the impact of dietary fiber on the intestinal health of human mothers and infants.

Screening for maternal cytomegalovirus infection during pregnancy and pregnancy outcome in patients with liver disease: an observational study

BackgroundCytomegalovirus (CMV) infection among pregnant females could induce CMV hepatitis with possible changes in liver stiffness measurement (LSM) which could be reversibly increased during normal pregnancies, particularly in the third trimester. This study aimed to detect the prevalence of CMV infection among pregnant females with and without chronic liver disease and to evaluate the effects of CMV infection on LSM and pregnancy outcomes in comparison to non-CMV-infected pregnant females.MethodsThis is an observational prospective study that included 201 pregnant ladies presented to the liver disease with pregnancy clinic, Cairo University from March 2018 to April 2019. We assessed the laboratory results, abdominal ultrasonography, LSM using ARFI elastography, and pregnancy outcomes.ResultsTwo hundred and one pregnant ladies were divided into ; group 1: pregnant ladies with normal pregnancy (n = 128), group 2: pregnant ladies with chronic liver diseases not related to pregnancy (n = 35), and group 3: pregnant ladies with pregnancy-related liver diseases (n = 38). Positive CMV serology (either/or, +ve CMV-IgM, IgG) was detected in 106/201 patients (52.74%), and fifteen of them had an active infection (IgG +, IgM+, PCR+). Pregnant females with chronic liver diseases not related to pregnancy had significantly higher serum levels of CMV IgM, IgG, and PCR. Moreover, LSM had a significant correlation with CMV IgG and CM_PCR in normal pregnant ladies. Maternal mortality occurred only in pregnant females with chronic liver diseases in 5.7% (2/35).ConclusionMaternal CMV infection carries a significant risk to pregnant females with chronic liver disease. Routine CMV screening for women planning to be pregnant, especially those with chronic liver disease could help to avoid bad maternal and fetal outcomes.

Functionally impaired antibody response to BNT162b2 booster vaccination in CVID IgG responders

Although previous studies described the production of IgG antibodies in a subgroup of patients with common variable immunodeficiency (CVID) following messenger RNA vaccinations with BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (CVID responders), the functionality of these antibodies in terms of avidity as measured by the dissociation rate constant (kdis) and the antibody response to booster immunization has not been studied. We sought to analyze in CVID responders and healthy individuals, the avidity of anti-SARS-CoV-2 serum antibodies and their neutralization capacity as measured by surrogate virus-neutralizing antibodies in addition to IgG-, IgM-, and IgA-antibody levels and the response of circulating (peripheral blood) follicular T-helper cells after a third vaccination with BNT162b2 SARS-CoV-2 messenger RNA vaccine. Binding IgG, IgA, and IgM serum levels were analyzed by ELISA in patients with CVID responding to the primary vaccination (CVID responders, n= 10) and healthy controls (n= 41). The binding avidity of anti-spike antibodies was investigated using biolayer interferometry in combination with biotin-labeled receptor-binding-domain of SARS-CoV-2 spike protein and streptavidin-labeled sensors. Antigen-specific recall T-cell responses were assessed by measuring activation-induced markers by flow cytometry. After the third vaccination with BNT162b2, IgG-, IgM-, and IgA-antibody levels, surrogate virus-neutralizing antibody levels, and antibody avidity were lower in CVID responders than in healthy controls. In contrast, anti-SARS-CoV-2 spike protein avidity was comparable in CVID responders and healthy individuals following primary vaccination. Follicular T-helper cell response to booster vaccination in CVID responders was significantly reduced when compared with that in healthy individuals. Impaired affinity maturation during booster response provides new insight into CVID pathophysiology.

Ophiopogonin D attenuates the progression of murine systemic lupus erythematosus by reducing B cell numbers.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune abnormalities leading to multi-organ damage. The activation of autoreactive B cell differentiation will lead to the production of pathogenic autoantibodies, contributing to the development of SLE. However, the effects of Ophiopogonin D (OP-D) on B cell activation and autoantibody production as well as renal injury in the pathogenesis of SLE remain unclear. MRL/lpr mice, one of the most commonly used animal models of SLE, were intragastrically administered with 5 mg/kg/d OP-D at 17 weeks of age for 3 weeks. The survival rates of mice in each group were monitored for 6 weeks until 23 weeks of age. Proteinuria and serum creatinine levels were measured. Serum levels of immunoglobulin (Ig)G, IgM, and anti-dsDNA autoantibodies were detected by enzyme-linked immunosorbent assay. Numbers of CD19+ B cells in the blood, spleen and bone marrow and numbers of splenic germinal center (GC) B cells were calculated by using flow cytometry. OP-D treatment prolonged survival in MRL/lpr mice. OP-D treatment reduced proteinuria and serum creatinine levels as well as mitigated renal pathological alternation in MRL/lpr mice. Furthermore, serum levels of IgG, IgM, and anti-dsDNA autoantibodies were reduced by OP-D treatment. OP-D lessened not only CD19+ B cells in the spleen and bone marrow but also plasma cells that secreted anti-dsDNA autoantibodies, IgG and IgM in the spleen and bone marrow. OP-D ameliorated the progression of SLE by inhibiting the secretion of autoantibodies though reducing B cell numbers.

CHARACTERISTICS OF THE IMMUNE STATUS IN PATIENTS WITH DECOMPENSATION OF LIVER CIRRHOSIS

Liver cirrhosis continues to be an acute problem of modern medicine due to the high rates of its prevalence and mortality. The high mortality rate is caused by the development of the number of life–threatening complications in decompensated forms of liver cirrhosis – hepatorenal syndrome, infections and varicose bleeding. Hepatorenal syndrome and infections are the result of immunological shifts occurring during decompensation of liver cirrhosis. Currently available literature data do not allow us to create a complete picture of the functional state of various links of adaptive immunity with decompensated liver cirrhosis. The aim of the research was to study the characteristic features of adaptive immunity in patients with decompensated liver cirrhosis. Material and methods. The prospective cohort study included 136 patients with decompensated liver cirrhosis, who received inpatient treatment in the hepatological department of the multidisciplinary hospital. The cohort of examined patients was divided into two groups, one of which included patients with liver cirrhosis of viral origin (n = 78), the other – patients with alcoholic liver cirrhosis (n = 58). In addition to the generally accepted standard methods, the patient examination program included immunological tests: identification of T- and B-lymphocytes, immunoregulatory and activated subpopulations of T-lymphocytes by the method of immunophenotyping peripheral blood mononuclear cells using monoclonal antibodies. The serum levels of immunoglobulins IgM, IgG, IgA, circulating immune complexes were determined by immunoturbidimetric method. Results. The study of indicators of the humoral link of adaptive immunity revealed an increase in the number of B cells, an increase in IgM, IgG, IgA and circulating immune complexes in patients with decompensated liver cirrhosis. The cellular link of adaptive immunity was characterized by an increase in the relative content of T helper cells, activated T cells against the background of a decrease in the number of immature T cells and T regulatory cells. Conclusions. The distinctive features of adaptive immunity in patients with decompensated liver cirrhosis are simultaneous activation of both humoral and cellular components, which, apparently, supports the systemic inflammatory process and the associated progressive liver fibrosis.

Pharmacokinetics and anti-ulcerogenic effects of Zuojin gastric floating bio-adhesive pellets in rats with acetic acid-induced gastric ulcer

Introduction: Zuojin pills(ZP) have been shown to be effective in the treatment of gastric ulcer (GU); however, the efficacy of Zuojin gastric floating bio-adhesive pellets(ZFP) in GU treatment is yet to be evaluated. Methods: The pharmacokinetics(PK) and protective effects of ZFP against acetic acid-induced GU was examined using rat models. Mass spectrometry(MS) analysis was performed using a TSQ LC-MS system. A total of 50male Sprague-Dawley(SD) rats were randomly assigned to five groups: normal, acetic acid-induced, positive control (rabeprazole, 2 mg/kg/day), ZP (500 mg/kg/day), and ZFP (500 mg/kg/day) groups, to elucidate the anti-ulcerogenic effect of ZFP. Results: ZFP prolonged the residence time of the drug (MRT, 10.88 ± 0.93 h; T1/2, 42.83 ± 2.56 h) in rats and promote the effective absorption of the drug with obvious sustained-release properties. Compared with the control group, ZFP treatment for 7 d significantly increased the weight of the rats, significantly reduced ulcer index, increased gastric tissue Superoxide dismutase(SOD) activity, reduced gastric tissue Malondialdehyde(MDA) content, and increased serum IgA, IgM, IgG, and Interleukin-2(IL-2) levels. Additionally, histopathological analysis showed that ZFP treatment reduced inflammatory cell infiltration to mainly the mucosal layer, anda small amount of fibrous scar proliferative repair was observed in the mucosal defect area and the underlying inflammatory granulation tissue. Conclusion: These results indicated that ZFP prolonged the residence time of the drug in rats with sustained-release properties and had an obvious protective effect against acetic acid-induced GU in rats.

Multimodal Imaging Characteristics and Risk Factors Analysis of Waldenström Macroglobulinemia Retinopathy

To summarize the multimodal imaging features and analyze the risk factors of Waldenström macroglobulinemia retinopathy (WMR). Retrospective, cross-sectional study. Patients diagnosed with Waldenström macroglobulinemia and underwent ophthalmic examination in Peking Union Medical College Hospital in the last decade were included. Multimodal imaging characteristics of WMR were summarized. Univariate and multivariate logistic regression analysis of WMR and potential systemic and ocular factors was performed. A total of 50 WM patients were included in this study, and 28 patients had WMR in at least one eye. WMR was found to have worse LogMAR visual acuity (VA) (0.52±0.54 vs. 0.21±0.18, p=0.009), and was characterized by tortuous retinal vessels, extensive retinal hemorrhage, and distinctive shape of macular edema, etc. In univariate analysis, the presence of WMR was significantly associated with the mean VA (LogMAR), serum RBC counts, serum PLT counts, HGB level, serum M protein, serum IgM level, and LDH (with p<0.05). In multivariate analysis, WMR was significantly correlated with M protein (adjusted OR=1.127, 95% CI 1.052-1.209, p= 0.001) and serum IgM (adjusted OR=1.059, 95% CI 1.023-1.095, p= 0.001) with the predicted AUC of 0.820 and 0.859, respectively. The optimal cut-off values were 26.2g/L for M protein, and 51.0g/L for IgM, which accounts for a sensitivity of 95.4% and 95.4%, and specificity of 64.3% and 60.7%. Retinopathy of WM has specific characteristics in ophthalmic examinations. Serum IgM levels and M protein are good predictors of WMR, which could attach important value of fundus examinations for WM patients.

Immunization effect of recombinant Lactobacillus casei displaying Aeromonas veronii Aha1 with an LTB adjuvant in carp

Aeromonas veronii is an important aquatic zoonotic, which elicits a range of diseases, such as haemorrhagic septicemia. To develop an effective oral vaccine against Aeromonas veronii infection in carp, the Aeromonas veronii adhesion (Aha1) gene was used as a target molecule to attach to intestinal epithelial cells. Two anchored recombinant. Lactic acid bacteria strains (LC-pPG-Aha1 1038 bp and LC-pPG-Aha1-LTB 1383 bp) were constructed by fusing them with the E. coli intolerant enterotoxin B subunit (LTB) gene and using Lactobacillus casei as antigen delivery vector to evaluate immune effects of these in carp. Western blotting and immunofluorescence were used to confirm that protein expression was successful. Additionally, levels of specific IgM in serum and the activities of ACP, AKP, SOD, LYS, C3, C4, and lectin enzymes-were assessed. Cytokines IL-10, IL-1β, TNF-α, IgZ1, and IgZ2 were measured in the liver, spleen, kidney, intestines, and gills tissue by qRT-PCR, which showed an increasing trend compared with the control group (P < 0.05). A colonization assay showed that the two L. casei recombinants colonized the middle and hind intestines of immunized fish. When immunized carp were experimentally challenged with Aeromonas veronii the relative percentage protection of LC-pPG-Aha1 was 53.57%, and LC-pPG-Aha1-LTB was 60.71%. In conclusion, these results demonstrate that Aha1 is a promising candidate antigen when it is displayed on lactic acid bacteria (Lc-pPG-Aha1 and Lc-pPG-Aha1-LTB) seems promising for a mucosal therapeutic approach. We plan to investigate the molecular mechanism of the L. casei recombinant in regulating the intestinal tissue of carp in future studies.

Immune Response Evaluation in Commercial Turkeys Affected with Clostridial Dermatitis.

Clostridial dermatitis (CD), caused by Clostridium septicum and Clostridium perfringens, is an economically important emerging disease of turkeys characterized by sudden deaths and necrotic dermatitis. Immune responses in CD-affected commercial turkeys are poorly understood. In the present study, C. septicum was isolated from CD-affected commercial turkeys during a recent outbreak, and the tissues (skin, muscle, and spleen) were collected and analyzed for immune gene expression, along with samples from clinically healthy birds. The results showed that CD-affected turkeys had significantly higher levels of IL-1β, IL-6, IFNγ, and iNOS transcripts in the skin, muscle, and spleen tissues compared to healthy birds. Affected turkeys also had a significantly elevated transcription of toll-like receptor (TLR21) gene in the skin and spleen tissues, suggesting a role for this receptor in the immune recognition. The expression of IL-4 and IL-13 genes in the spleen and muscle was also significantly higher in the affected birds. Additional birds from the same affected and healthy farms examined for serology revealed that the CD-affected turkeys had significantly higher levels of serum IgM and IgY antibodies. Furthermore, in vitro stimulation of MQ-NCSU macrophages with C. septicum led to a significant transcriptional upregulation of IL-1β and IFNγ genes, while the IL-10 gene expression was downregulated. The surface expression of MHC-II protein and cellular production of nitric oxide were also significantly increased in the C. septicum-stimulated macrophages, indicating cellular activation. Collectively, our findings suggest that the host responses in CD-affected turkeys involve a robust inflammatory response as well as a response mediated by IL4/IL-13 cytokines that may aid in antibody-mediated immunity.