Serum IgA Levels Research Articles

Comparison of Immunoglobulins Status In Splenectomized And Non-Splenectomized Patients With Major Beta-Thalassemia

Background: Thalassemia is one of the most prevalent genetic disorders globally, and infections are one of the major causes of death in these patients. Various studies have attributed the increased susceptibility to bacterial infections in thalassemia patients to changes in their immunological status. Objectives: This research aimed to measure serum levels of immunoglobulins (Igs) in Thalassemia Major (TM) patients and in the control group. Methods: The study included forty TM patients (20 splenectomized and 20 non-splenectomized) and 20 healthy participants (the control group). Three groups were matched for age and gender. Mean serum levels of immunoglobulins (IgG, IgA and IgM) were measured for all individuals by ELISA. P<0.05 was considered the significance level. Results: Increased serum IgG and IgA levels and significantly reduced serum IgM levels were observed in the splenectomized patients compared to the non-splenectomized ones. A comparison of the study groups revealed that serum IgG and IgA levels in the splenectomized patients and the mean serum IgM and IgG levels in the non-splenectomized patients were higher than those of the healthy participants. The mean serum IgM levels in the splenectomized patients and the mean serum IgG levels in the non-splenectomized patients were lower than those of the control group. Conclusions: The results showed that splenectomy could change the immunological status of thalassemia patients. Nevertheless, the exact mechanism for this change was not clear. Studying the serum levels of immunoglobulins might be useful in determining the severity of infections in TM patients.

Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial.

Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia. This is a prospective cohort study. This study was conducted at our hospital. We analyzed stroke patients with dysphagia. A total of 120 stroke patients with dysphagia were randomly divided into a routine group and a test group, with 60 cases in each group. Routine swallowing training was performed in the routine group, and the test group was stimulated with vitamin C acid. The water swallow test (WST) and video fluoroscopic swallowing study (VFSS) were used to compare the rehabilitation of dysphagia in the two groups. Nourishment State Index was evaluated by BMI, serum albumin, total serum protein and hemoglobin. Immune Function Index was evaluated by IgA, IgM and IgG. Compared with the control group, the WST level of patients treated with vitamin C acid stimulation intervention were significantly reduced, and the VFSS score were significantly increased. Serum levels of hemoglobin, albumin, total protein, IgA, IgM and IgG in the vitamin C acid stimulation group were remarkably increased than those in the control group. Vitamin C acid stimulation exhibits a good application effect in patients with dysphagia after stroke. Moreover, vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote postoperative recovery of patients. Therefore, we believe that vitamin C stimulation therapy can be widely used in stroke rehabilitation management. Vitamin C acid stimulation significantly improves rehabilitation of stroke patients with dysphagia and ameliorates the nutritional status and immune function of patients.

Extramucosal Formation and Prognostic Value of Secretory Antibodies in Rheumatoid Arthritis.

To investigate levels and possible extramucosal formation of secretory Ig, including anti-citrullinated protein antibodies (ACPAs), in rheumatoid arthritis (RA). Three patient groups were studied: 1) ACPA-positive patients with musculoskeletal pain without clinical arthritis, 2) patients with recent-onset RA, and 3) patients with established RA. In baseline serum samples (groups 1 and 2) and paired synovial fluid samples (group 3), we analyzed total secretory IgA, total secretory IgM, free secretory component (SC), and SC-containing ACPA. Extramucosal formation of SC-containing ACPA was investigated by preincubating RA sera and affinity-purified ACPA with recombinant free SC. Compared to healthy controls, serum levels of total secretory IgA and total secretory IgM were increased both in patients with early RA and at-risk patients (P < 0.05). Patients with early RA with elevated total secretory Ig had significantly higher disease activity during the 3-year follow-up period compared to those without increased levels. At-risk patients who developed arthritis during follow-up (39 of 82) had higher baseline total secretory IgA levels compared to those who did not (P = 0.041). In established RA, total secretory IgA and total secretory IgM levels were higher in serum than in synovial fluid (P < 0.0001), but SC-containing ACPAs adjusted for total secretory Ig concentration were higher in synovial fluid (P < 0.0001). Preincubation with recombinant free SC yielded increased SC-containing ACPA reactivity in sera as well as in affinity-purified IgA and IgM ACPA preparations. Circulating secretory Ig are elevated before and at RA onset. In the presence of free SC, secretory Ig may form outside the mucosa, and SC-containing ACPAs are enriched in RA joints. These findings shed important new light on the mucosal connection in RA development.

Effects of synbiotic on growth, digestibility, immune and antioxidant performance in broilers

The overuse of in-feed antibiotics has been associated with serious issues, including the developing of antibiotic-resistant pathogens and causing drug residues in poultry products. To date, many countries have restricted the use of growth-promoting antibiotics in food animals, resulting in the increased need for effective alternatives to in-feed antibiotic. Synbiotics, which are composed of probiotics and prebiotics, have been shown to act synergistically when applied simultaneously. Thus, this study investigated the effects of a synbiotic, composed of microencapsulated Lactobacillus plantarum (MLP) and fructooligosaccharide (FOS), on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus in broilers. A total of 168 newly hatched male broilers were randomly allotted to three dietary groups (n = 7): (1) a corn-soybean meal basal diet (CON); (2) basal diet + synbiotic (SYN); and (3) basal diet + aureomycin (ANT). Compared with the CON, chickens had greater average daily gain and digestibility of calcium and phosphorus in the SYN group (P < 0.05). In the SYN and ANT group, serum IgA, IgG, and IL-10 levels were higher, while the serum TNF-α, IL-2, and IL-6 levels were reduced (P < 0.05) compared to CON. Compared with CON, the level of serum malondialdehyde was lower (P < 0.05) and SOD level was higher (P < 0.05) in either SYN or ANT group. No significant differences in populations of Escherichia coli were seen in chickens among the three groups, whereas, the populations of Lactobacillus were higher (P < 0.05) in chickens in the SYN group compared with those in CON and ANT groups. Taken together, the addition of SYN, consisting of MLP and FOS, had benefits on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus, indicating its potential to serve as a substitute for antibiotics in broiler feeding.

Deficiencia de IgA y comorbilidades autoinmunes en la artritis idiopática juvenil

Objectives(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentre cohort of patients with juvenile idiopathic arthritis (JIA), and (2) to assess whether patients with JIA and IgAD have additional autoimmune disorders more frequently than patients with JIA and normal serum levels of IgA. MethodsRetrospective chart review of a cohort of patients with JIA managed in the paediatric rheumatology units of 2hospitals in Madrid, Spain. ResultsThis study included 193 patients, 123 (64%) female. The median age at disease onset was 5.6 years (IQR 2.5–9.7) and the median duration of followup was 5.1 years (IQR 2.2–8.1). The 3most common categories of JIA based on the ILAR classification were oligoarticular (53%), poliartritis RF-negative (20%) and enthesitis-related arthritis (10%). Serum IgA levels were available in 172/193 (89%); 25/172 (15%) had selective (<7mg/dl, n=8) or partial (7-69mg/dl, n=17) IgAD. All patients underwent periodic ophthalmic examinations. Eighteen children (9%) had anterior uveitis, which was chronic in 15 and acute in 3. Serum levels of anti-transglutaminase IgA, or IgG in IgAD were obtained in 135/193 (70%). Four children (3%) were diagnosed with CD either by intestinal biopsy (n=3) or by the combination of characteristic clinical, serological and genetic features (n=1); 2of them had IgAD (OR=6.4; 95% CI, 0.9–47.6; p=.12). Only 1 of these 153 patients (0.7%) had hyperthyrotropinaemia with positive anti-thyroid antibodies and required replacement therapy. ConclusionPatients with JIA frequently present autoimmune comorbidities. IgAD does not seem to increase their prevalence, with the possible exception of CD.

Analysis of Serum IgG1 to Predict Progression and Therapeutic Effect in Patients with Multiple Myeloma.

Objective The correlation between laboratory indicators and clinical treatment effects and the prognosis of multiple myeloma remains poorly understood. Therefore, our study investigated whether serum IgG subclasses could be employed as potential indicators contributed to evaluate the therapeutic effect and prognosis of patients with multiple myeloma. Patients and Methods. Records of patients with multiple myeloma were initially diagnosed at the First Affiliated Hospital of Soochow University, China, from August 1, 2017, to February 28, 2020. The assessment abilities of serological indicators for therapeutic effect were evaluated in patients compared with healthy controls. Results In 560 study patients with multiple myeloma, serum IgA, IgG, IgM, κ-LC, and λ-LC increased by15%, 33.04%, 1.96%, 27.50%, and 26.43%, respectively. Further analysis found that IgG1, IgG2, IgG3, and IgG4 were over the upper limit of the reference range with 26.38%, 6.09%, 8.12%, and 4.64%, respectively. κ-LC and λ-LC were found in the urine in 65.13% and 29.70%, respectively. In peripheral blood, the proportion of CD3+CD4+, CD3−CD19+ cells, and CD4+/CD8+ decreased, whereas CD3+CD8+ cells and CD16+/CD56+ increased, and the associated cytokines IL-2, IL-4, IL-6, TNF-α, and IFN-γ were upregulated in patients when compared with healthy controls. Furthermore, the serum levels of IgA, IgG, IgG1, IgG2, IgG3, and IgG4 gradually decreased in patients before, during, and after treatment. Similar results were found in serum and urine κ-LC and λ-LC. Conclusion Serum IgG1 level could serve as the potential indicator for evaluating the therapeutic effect for patients with multiple myeloma. κ-LC and λ-LC also have the potential to be prognostic indicators. More studies are warranted to explore these serological indicators for personalized therapy in the future.

Novel Synthetic Lipopeptides as Potential Mucosal Adjuvants Enhanced SARS-CoV-2 rRBD-Induced Immune Response.

As TLR2 agonists, several lipopeptides had been proved to be candidate vaccine adjuvants. In our previous study, lipopeptides mimicking N-terminal structures of the bacterial lipoproteins were also able to promote antigen-specific immune response. However, the structure-activity relationship of lipopeptides as TLR2 agonists is still unclear. Here, 23 synthetic lipopeptides with the same lipid moiety but different peptide sequences were synthesized, and their TLR2 activities in vitro and mucosal adjuvant effects to OVA were evaluated. LP1-14, LP1-30, LP1-34 and LP2-2 exhibited significantly lower cytotoxicity and stronger TLR2 activity compared with Pam2CSK4, the latter being one of the most potent TLR2 agonists. LP1-34 and LP2-2 assisted OVA to induce more profound specific IgG in sera or sIgA in BALF than Pam2CSK4. Furthermore, the possibility of LP1-34, LP2-2 and Pam2CSK4 as the mucosal adjuvant for the SARS-CoV-2 recombinant RBD (rRBD) was investigated. Intranasally immunized with rRBD plus either the novel lipopeptide or Pam2CSK4 significantly increased the levels of specific serum and respiratory mucosal IgG and IgA, while rRBD alone failed to induce specific immune response due to its low immunogenicity. The novel lipopeptides, especially LP2-2, significantly increased levels of rRBD-induced SARS-CoV-2 neutralizing antibody in sera, BALF and nasal wash. Finally, Support vector machine (SVM) results suggested that charged residues in lipopeptides might be beneficial to the agonist activity, while lipophilic residues might adversely affect the agonistic activity. Figuring out the relationship between peptide sequence in the lipopeptide and its TLR2 activity may lay the foundation for the rational design of novel lipopeptide adjuvant for COVID-19 vaccine.

In Vivo Recovery of Bacteriophages and Their Effects on Clostridium perfringens-Infected Broiler Chickens.

The objectives of this study were to recover bacteriophages (BPs) from the intestinal digesta of BP-fed broilers and to evaluate the antibacterial effects of encapsulated or powdered BPs in broiler chickens challenged with Clostridium perfringens. Day-old broiler chicks (n = 320/experiment) were randomly assigned to 32 pens (n = 10 broilers/pen) and allocated to one of four dietary groups: (1) unchallenged group (NEG); (2) C. perfringens-challenged group (POS); (3) POS group fed a diet supplemented with powdered BPs; and (4) POS group fed a diet supplemented with encapsulated BPs. On days 21, 22, and 23 post-hatch, all chickens except NEG were orally inoculated twice a day with 2 mL C. perfringens (1.0 × 108 cfu/mL). Varying BP levels were detected in gut digesta at all ages and were numerically or significantly higher in the encapsulated BP group than in the powdered BP group. Dietary powder or encapsulated BPs reversed the C. perfringens-mediated increase in crypt depth. In addition, villus height to crypt depth ratio was elevated in the NEG and BP-treated/challenged groups compared with that in the POS group. C. perfringens counts in the cecum were significantly lower in the BP-fed chickens than in the POS group. The encapsulated BP-supplemented diet-fed chickens had the highest serum IgA levels. Collectively, our results suggest that dietary BP remains viable in intestinal digesta upon ingestion and can inhibit cecal C. perfringens counts.

Let-7a Targeting TNFAPI3 Promotes Vascular Endothelial Cell Apoptosis of Pediatric Patients with Henoch-Schönlein Purpura via NF-κB Signaling Pathway.

Objective We aimed at exploring the role of let-7a in the pathogenesis of pediatric Henoch–Schönlein purpura (HSP) and its related mechanism. Methods Fifty-five pediatric HSP patients and 20 paired healthy controls were included. The expressions of let-7a and TNFAIP3 were detected by RT-qPCR or/and western blot. Vessel fibrinoid necrosis was evaluated in skin tissues by PTAH staining. The serum IgA level was measured by ELISA. Cells were transfected with let-7a inhibitor and/or TNFAIP3 siRNA, accompanied by pretreatment with NF-κB inhibitor PDTC or not. After being cultured in HSP serum, the changes in cell viability, cell apoptosis, apoptosis-related proteins, and NF-κB pathway-related proteins were detected by CCK8, flow cytometry, and western blot. Results The let-7a expression level was positively correlated with the serum IgA level and severity degree of vascular fibrinoid necrosis in HSP patients. Let-7a expression was significantly increased, whereas cell viability and TNFAIP3 expression were obviously decreased 48 h after HUVECs were incubated with HSP serum. Let-7a knockdown upregulated the cell viability, whereas it reduced the apoptotic ratio, apoptosis protein expressions (Bax/Bcl2 ratio, cleaved-caspase 3), and NF-κB pathway activation (reflected by reduced P65 nuclear translocation and p-IκBα expression) in HUVECs (all p < 0.05). The changes induced by let-7a knockdown were obviously reversed by TNFAIP3 siRNA transfection (p < 0.05). Besides, PDTC treatment remarkably diminished the anti-apoptosis effect of let-7a knockdown and pro-apoptosis effect of TNFAIP3 siRNA on HUVECs induced by HSP serum. Conclusions Let-7a knockdown significantly suppressed vascular endothelial cell apoptosis induced by HSP serum by targeting TNFAPI3 via NF-κB signaling pathway. Our findings provided a potential therapeutic target for the treatment of HSP.

Evaluation of immune response and haematological parameters in infected male albino rats by giardiasis.

The present work aimed to study the effects of Giardia lamblia infection on immunological and haematological studies and to evaluate immunoglobulins and some cytokines. Fifty male albino rats were divided into six groups. The control group includes 20 rats and the infected group includes 30 rats. All the estimations were checked all over five checkpoints (CP) (7, 14, 21, 28 and 35days post-infection). Serum levels of IgA, IgG, IgM and IgE. Cytokines INF-γ, TNF-alpha, IL-4, IL-10 and haematological parameters were determined. Cyst and trophozoite were counted. A considerable increase in the level of immunoglobulins and cytokines in all infected groups compared with the control group was documented. Furthermore, a significant decrease in red blood corpuscles, haemoglobin and mean corpuscular haemoglobin concentration levels was observed, whereas substantial increases in mean corpuscular volume, mean corpuscular haemoglobin and platelets were observed. Moreover, infected rats had a substantial rise in WBCs, lymphocytes and eosinophil counts compared with the control group, whereas neutrophils and monocytes had a significant decrease. The number of trophozoites and cysts was significantly increased in infected groups before diminishing after day 28. The current results showed that Th1 and Th2 immune responses, which are characterized by the production of TNF-α, IFN-γ, IL-4 and IL-10, are important for protection against Giardia infections and also verified the balance between these cytokines and the timing of their production was crucial in G.lamblia immune response.

Evaluation of immunoglobulin M and A level in individuals with HIV-TB co-infection in NAUTH, Nnewi

This study evaluated the serum concentrations of Immunoglobulin M and Immunoglobulin A in individuals with TB, HIV and HIV-TB co-infection in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi South East, Nigeria. A total of 80 participants (males=44; females=36), with a mean age of 35.83±7.3 were randomly recruited by convenient sampling technique from patients attending TB-DOTS and HIV Clinics in NAUTH and grouped as: TB positive individuals (Group I), HIV-TB co-infection (Group II), HIV positives (Group III), and control (Group IV). 5mls of venous blood samples were collected from each participants using plain containers for estimation of immunoglobulin A and M classes by Immuno-turbidimetric Method. The results obtained showed that mean serum levels of IgM (78.14±42.41 and IgA (374.45±15.69) were significantly increased in participants with HIV-TB co-infection when compared with TB (49.21±3.67) and (315.41±52.79), HIV (41.91±25.97) and (342.23±92.67 and control groups (55.82±35.36) and (322.66±71.34) at p&amp;#60;0.05 respectively. There were significant increases in the mean serum IgM (p=0.048), IgA (p=0.000) and age (p=0.001) when group I participants were compared with group II individuals respectively, while IgM showed significant increase (p=0.013) in group II than in group III only. Furthermore, participants in group II showed significantly increased mean serum IgA levels compared to control (p=0.005), whereas significant negative correlations were seen in age and gender in various groups studied (p&amp;#60;0.05). Thus, evaluation of these antibodies may be used alongside other systemic markers and parameters to aid in predicting disease severity and progression and also monitoring response to treatment. This approach could further complement the current TB management especially in HIV-TB co-infection.

Effects of substituting soybean meal with corn on immune function and gene expression of gut TLR4 pathway of growing goats.

BackgroundProtein malnutrition remains a severe problem in ruminant production and can increase susceptibility to infection, especially during the growth stage. This study aimed to explore substituting soybean meal with corn on activation of the TLR pathway and potential impact on immune response bias towards Type 1 or Type 2 using growing female goats as experimental animals.MethodsTwenty-four Xiangdong black goats (initial BW = 19.83 ± 0.53 kg, about 8 ± 0.3 months old) were selected and randomly divided into the corn-soybean meal basal diet group (CON, 10.77% protein) and replacing soybean meal with 100% of corn group (CRS, 5.52% protein). EDTA whole blood and serum samples were collected prior to slaughter for determinations of blood cell counts, anti-inflammatory cytokines and antibodies. The duodenum, jejunum, ileum and colon tissues were collected after formal trial to study the effect of CRS diet on the expression of TLR4 pathway.ResultsOur results showed CRS diet did not induce a significant change in immune function, as evidenced by the observations that white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), monocyte (Mon), eosinophil (Eos), interleukin-4 (IL-4), IL-5, IL-13, immunoglobin G (IgG), IgA, and IgM levels in serum were similar between the two groups. RT-PCR results showed the expression of tumor necrosis factor-α (TNF-α) (P < 0.01) and interferon-β (IFN-β) (P < 0.01) were up-regulated in the colon of goats in the CRS group. No differences in the expression of myeloid differentiation factor 88 (MyD88) adaptor-like protein (TIRAP), IL-1 receptor–associated kinase 1 (IRAK1), TNF receptor related factor 6 (TRAF6), NF-kappa B (NF-κB), mitogen-activated protein kinase 1 (MAPK1) or activator protein-1 (AP-1) in the TLR4/MyD88 dependent pathway were observed between the two groups for any of the tested tissue. However, the expression of NF-κB activator (TANK) binding kinase 1 (TBK1) in TLR4/MyD88 independent pathway was up-regulated in the duodenum and colon (P < 0.01), and the expression of interferon regulatory factor-3 (IRF3) was up-regulated (P < 0.01) in colon.ConclusionsOur results suggested that the CRS diet failed to induce a significant change in innate immunity and adaptive immunity in growing goats. However, the up-regulated TBK1 and IRF3 in the colon from the CRS goats suggests that the CRS diet may induce the expression of Th1-type proinflammatory cytokines and inflammatory response through a TLR4-MyD88-independent pathway, and the colon may be the easiest targeted section in the intestinal tract.

POS-109 INTERIM RESULTS OF PHASE 1 AND 2 TRIALS TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND CLINICAL ACTIVITY OF BION-1301 IN PATIENTS WITH IgA NEPHROPATHY

IgA nephropathy (IgAN) is an autoimmune disease with no approved treatments. A critical step in IgAN pathogenesis is the production of galactose-deficient IgA1 (Gd-IgA1) leading to the generation of anti-Gd-IgA1 autoantibodies and the formation of immune complexes that result in kidney inflammation and damage. A Proliferation-Inducing Ligand (APRIL), a soluble factor that regulates B cell differentiation, proliferation and survival of plasma cells, and IgA class-switching is elevated in patients with IgAN. IgAN patients with high plasma APRIL levels are reported as having higher levels of Gd-IgA1 and proteinuria and lower estimated glomerular filtration rates compared to those with lower plasma APRIL levels. BION-1301 is a novel humanized blocking antibody targeting APRIL that has been evaluated in a Phase 1 study of healthy volunteers (HV). In that study, BION-1301 was well-tolerated with no serious adverse events (SAEs), a pharmacokinetic (PK) half life >30 days and demonstrated dose-dependent pharmacodynamic (PD) effects characterized by durable reductions in serum levels of free April (fAPRIL), IgA and Gd-IgA1, IgM, and to a lesser extent IgG. Here we present interim results from Part 3 of the Phase 1 and the Phase 2 Open-Label Extension (OLE) trials that characterize the safety, PK and PD profile, and preliminary efficacy of BION-1301 in patients with IgAN. The Phase 1 study (NCT03945318) comprises 3 parts. Parts 1 and 2 assessed single- and multiple ascending doses of BION-1301 in HV from 10mg to 1350mg and 50mg to 450mg once every 2 weeks for one month, respectively. Part 3 is an ongoing, open-label, two cohort design in approximately 20 IgAN patients with BION-1301 at 450mg once every 2 weeks for a total of 12 weeks. Key eligibility criteria for Part 3 include: (1) biopsy-verified diagnosis of IgAN within the past 10 years,(2) urine protein ≥0.5 g/24h or baseline UPCR ≥0.5 g/g, and (3) stable/optimized dose of ACE-I/ARB (or intolerant). Patients completing Part 3 are eligible to enroll in the Phase 2 OLE study (NCT04684745) to receive BION-1301 for an additional 2 years. To evaluate PK and PD effects of BION-1301, serum levels of BION-1301, fAPRIL, antidrug antibodies (ADA), neutralizing antibodies (NAbs), and Gd-IgA1 were quantitated using ELISA-based immunoassays. Serum levels of IgA, IgG, and IgM were measured by immunoturbidimetry. UPCR was assessed from 24-hour urine collections. BION-1301 has been well tolerated in IgAN patients receiving a 450mg IV dose every two weeks for 12+ weeks with no SAEs or treatment related AE’s. Consistent with PD responses reported in HVs, durable reductions in serum levels of fAPRIL and immunoglobulins were observed in IgAN patients. Clinically meaningful reductions in proteinuria were seen as early as 12 weeks and were associated with the reduction in Gd-IgA1 levels. Additional data from patients receiving long-term treatment will be updated. This abstract was also submitted for the 58thERA-EDTA Congress. BION-1301 offers disease modifying potential by directly targeting the underlying multi-hit immune pathogenesis of IgAN, which is not addressed with the current standard of care treatment. Promising early biomarker and clinical activity responses support the continued development of BION-1301 in IgAN.

РОЛЬ ИММУНОЛОГИЧЕСКИХ ФАКТОРОВ В НЕБЛАГОПРИЯТНОМ ИСХОДЕ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНИ ЛЕГКИХ

Aim. The aim of the research was to study the role of immunological mechanisms in the unfavorable outcome of chronic obstructive pulmonary disease (COPD). Material and methods. The research included 116 patients hospitalized in 2005-2006 in the pulmonology department of patients with the exacerbation of mild and moderate COPD. Research protocol: general clinical and special (immunological) methods of examination were performed in patients with COPD. Instrumental research methods included: spirography, ECG, EchoCG, fibrobronchoscopy, chest X-ray. After diagnostic bronchoscopy, bronchoalveolar fluid (BAF) was taken for cytological and immunological examination. On the first and second days of inpatient treatment, patients underwent immunological studies: immunophenotyping of mononuclear cells (MNC), assessment of phagocytic activity of leukocytes (latex test, nitroblue tetrazolium (NBT) test) in blood and BAF, determination of the content of immunoglobulins in blood serum and BAF, study of cytokine levels in blood serum, BAF and MNC culture supernatant under conditions of their spontaneous production and activation in the mitogen-stimulated (phytohemagglutinin "Difco" 5 mg/ml) proliferation. Statistical data processing was carried out using the Statistica 10.0 program. In 2020, the long-term survival of COPD patients was assessed. The cohort of patients was divided into two groups. Survivors were included in the first group (n=44), and patients who died by 2020 were included in the other group (n=72). The retrospective comparison of the studied indicators was determined at the time of COPD exacerbation in 2005- 2006 in these patient groups. Results and discussion. In the surviving patients, the BAF cytogram was distinguished by the higher macrophage content and the increased number of NBT-positive cells in this population with the reduced neutrophil content in both blood and BAF. The deceased had elevated levels of IgM and IgA in the blood serum and BAF. The results of the study of cytokine production in MNC cultures in vitro indicate that the ratio of IFN-γ/IL-4 in the conditions of spontaneous cytokine production was higher in the deceased compared with the indicators of the surviving patients. This fact indicates the polarization of the immune response of the deceased in the direction of the cell type mediated by Th1 cells, which is confirmed by the peculiarities of the BAF cytokine profile in the deceased – the significant increase in the value of IFN-γ/IL-4 relative to the indicators in the survivors. Conclusion. The unfavorable outcome of COPD is associated with the increase in the number of neutrophil cells in BAF, in the blood, with the predominance of Th1-type activation of adaptive immunity at the local level and activation of both cellular and humoral mechanisms of adaptive immunity at the systemic level. The increased activity of innate immunity in COPD exacerbation, manifested by the increase in the number and metabolic activity of macrophages, is associated with the long-term survival of patients.

Implications potentielles du système IgA-pIgR dans la fibrose pulmonaire idiopathique

Idiopathic pulmonary fibrosis (IPF) is a lethal respiratory disease characterized by the excessive deposition of extracellular matrix in the alveolar zones. The bronchiolar epithelium has been implicated in the development of this disease and is capable of secreting IgA into the airway lumen thanks to its expression of the polymeric immunoglobulin receptor. Several elements indicate a dysregulation of this system, such as raised serum IgA levels in IPF patients and the pro-fibrotic effect of IgA on several key cell types. Our work aims at studying the underlying mechanisms so as to better understand the role of IgA mucosal immunity in this disease.

Vaccination of mice with hybrid protein containing Exotoxin S and PcrV with adjuvants alum and MPL protects Pseudomonas aeruginosa infections

Pseudomonas aeruginosa as a common pathogen causing urinary tract infections (UTIs) has been resistant to different antibiotics and developing an effective vaccine can be an alternative strategy. In the present study, the immunogenicity and protection efficacy of formulations composed of a hybrid protein composed of P. aeruginosa V-antigen (PcrV) and exoenzyme S (ExoS) with alum and MPL were evaluated. The hybrid protein could increase the specific systemic and mucosal immune responses, as well as cellular responses as compared with control groups. Combining of alum or MPL adjuvant with the hybrid protein significantly improved the levels of IgG1, serum IgA, mucosal IgG, and IL-17 as compared to the ExoS.PcrV alone. After bladder challenge with a P. aeruginosa strain, the bacterial loads of bladder and kidneys were significantly decreased in mice received ExoS.PcrV admixed with alum and ExoS.PcrV admixed with MPL than controls. The present study indicated that immunization of mice with a hybrid protein composed of ExoS and PcrV could induce multifactorial immune responses and opsonize the bacteria and decrease the viable bacterial cells. Because P. aeruginosa have caused therapeutic challenges worldwide, our study proposed ExoS.PcrV + alum and ExoS.PcrV + MPL as promising candidates for the prevention of infections caused by P. aeruginosa.

DOP51 Loss of PTPN23 in the intestinal epithelium results in epithelial hyperproliferation and lethal diarrhea in a microbiota dependent manner

Abstract Background Protein tyrosine phosphtase non-receptor type 23 (PTPN23) plays a critical role in regulating epidermal growth factor (EGF) receptor signaling and its loss has been associated with aberrant cell proliferation and promotes onset of epithelial cancers. However, the role of PTPN23 in the intestinal epithelium has not been investigated yet. Here, we investigated how PTPN23 deletion in intestinal epithelial cells (IEC) affects intestinal homeostasis. Methods To study the role of PTPN23 in the intestinal epithelium, we crossed mice with a LoxP flanked PTPN23 gene (PTPN23fl/fl mice) to mice expressing the CreERT construct under the villin promoter (PTPN23-VilCreERT mice). PTPN23 was deleted in IEC in these mice by tamoxifen-injections on five consecutive days. PTPN23 fl/fl mice injected with tamoxifen served as control. Results PTPN23 deletion in IEC resulted in drastic loss of weight starting around 10-14days after the first tamoxifen injection, eventually leading to death within 3–5 weeks due to severe wasting disease with severe diarrhea. Histology revealed massive hyper-proliferation of the colonic epithelium accompanied with elevated immune cell infiltration. In line with previous reports on the function of PTPN23, we observed highly elevated levels of EGF receptor, possibly accounting for the massive epithelial hyper-proliferation and aberrant water secretion/defective water resorption in these mice. Furthermore, we observed bacterial translocation to the spleen and the liver, indicating defective anti-bacterial defense in the intestinal epithelium of PTPN23-VilCreERT mice. In line with this, 16S sequencing revealed significant differences in the intestinal microbiome with an overgrowth of bacteria that have been reported to be heavily coated with IgA. PTPN23-VilCreERT mice showed reduced apical presence of the poly Ig receptor, a receptor that transports IgA from the lamina propria through IEC into the gut lumen. Notably, while serum IgA levels were normal, its levels in the stool were reduced, confirming defective transport of IgA into the gut lumen. In addition, autophagy was significantly reduced in PTPN23-VilCreERT mice when compared to their littermates. Of interest, antibiotic treatment was sufficient to prevent epithelial hyper-proliferation, diarrhea and death in PTPN23VilCreERT mice, indicating that this drastic phenotype was microbiota-dependent and likely the result of defects in bacterial handling. Conclusion Our results demonstrate that PTPN23 is indispensible for normal IEC function and its loss renders the intestinal epithelium unable to cope with invading bacteria. This uncovers a novel, so far unknown role of PTPN23 for regulating pathways involved in bacterial handling.

Memory B cells and serum immunoglobulins are associated with disease severity and mortality in patients with COVID-19

Purpose of the studyThe aim of this study was to investigate the relationship of B cell-mediated immunity with disease severity and mortality in patients with COVID-19.Study designIn this retrospective cohort...

Age and Primary Vaccination Background Influence the Plasma Cell Response to Pertussis Booster Vaccination.

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. Here, 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. Participants were divided over four age cohorts. We compared longitudinal kinetics within each cohort and between the different cohorts. Changes in the B-cell compartment were correlated to numbers of vaccine-specific B- and plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days postvaccination was the most prominent cellular change in all age groups and was most pronounced for more mature IgG1+ plasma cells. Plasma cell responses were stronger in individuals primed with whole-cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ and IgA1+ plasma cell expansion correlated with FHA-, Prn-, or PT- specific serum IgG or IgA levels. Our study indicates plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and primary vaccination backgrounds.

Selenium-Enriched Yeast Relieves Hexavalent Chromium Toxicity by Inhibiting NF-κB Signaling Pathway in Broiler Spleens.

Simple SummaryHexavalent chromium is a common environmental pollution. It has been reported that hexavalent chromium threatens the health of humans and animals, so it is necessary to develop new, effective mitigation methods. Selenium is an indispensable micronutrient recently shown to be able to resist the toxicity of heavy metals. Selenium-enriched yeast has a high content of total selenium, which has the advantages of a high absorption rate and safety. Potassium dichromate and selenium-enriched yeast were used to construct single hexavalent chromium and combined selenium/hexavalent-chromium-exposed broiler models. Additionally, the ability to relieve the hexavalent chromium toxicity of selenium along with the molecular mechanisms focusing on inflammation induced by the NF-κB signaling pathway was investigated in this study. Histopathological assessment, serum biochemical tests, oxidative stress kits, enzyme-linked immunosorbent assay, quantitative real-time PCR, and Western blotting were used to detect indicators. We found that the oxidative stress induced by hexavalent chromium triggers NF-κB pathway-driven inflammatory responses in the broiler spleen and further reduces the immune function of broilers. Selenium-enriched yeast protects the spleen from the toxicity of hexavalent chromium exposure through inhibiting the NF-κB signaling pathway.This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr6+)-induced toxicity. Potassium dichromate (K2Cr2O7) and selenium-enriched yeast (SeY) were used to construct the single Cr6+ and combined Se/Cr6+ exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr6+ group, and Cr6+ group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr6+ were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr6+ group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr6+; however, these changes were mitigated by Se/Cr6+ exposure. Importantly, Cr6+ exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr6+group. Furthermore, Cr6+ significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Cr6+group than in the Cr6+ group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr6+ groups, while they were downregulated in Se/Cr6+ group compared to that in Cr6+ group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr6+ exposure, but the SeY supplement relived the expression levels mediated by Cr6+ exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr6+, and we speculate that the NF-κB signaling pathway is one of its mechanisms.