Total IgA Concentrations Research Articles

Immunoadsorption as a method of antibody donation during the COVID-19 pandemic.

Initial therapeutic efforts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included the use of plasma from convalescent donors containing anti-SARS-CoV-2 antibodies. High-neutralizing antibody titres are required for therapeutic efficacy. This study aims to show that immunoadsorption followed by tangential flow filtration can be used to obtain antibody concentrates with high-neutralizing capacities. Eligible donors (n = 10, five males and three females) underwent immunoadsorption using adsorber columns specific for human antibodies. Glycine-washed out eluates of 1.5 L volume were further concentrated by tangential flow filtration using 30 kDa ultrafiltration membranes. The same membranes were applied for diafiltrations to exchange residual glycine for 0.9% normal saline. Antibody concentrates were obtained within 8 h from the start of donation and had 4.58 ± 1.95, 3.28 ± 1.28 and 2.02 ± 0.92 times higher total IgG, IgA and IgM concentrations, 3.29 ± 1.62 and 3.74 ± 0.6 times higher SARS-CoV-2 N and S antibody concentrations and 3.85 ± 1.71 times higher SARS-CoV-2 S-specific IgG concentrations compared to the donors' peripheral blood. The specific SARS-CoV-2 virus neutralization capacities increased in all but one concentrate. All antibody concentrates (50-70 mL final volume) passed microbiological tests, were free of hazardous glycine levels and could be stored at -80°C and 4°C for 1 year with 20 ± 3% antibody loss. Immunoadsorption followed by tangential flow filtration is a feasible procedure to collect IgG, IgA and IgM as well as SARS-CoV-2 N- and S-specific antibody concentrates of low volume, free of albumin and coagulation factors. Whether these concentrates can be used as passive immunisation in infected patients remains to be elucidated.

Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597). Icelandic population of adults aged 40 years or older. 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. The prediction model will require external validation. This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. International Myeloma Foundation and the European Research Council.

Major low-energy trauma results in non-specific immunoglobulin generation without evidence for specific autoantibody production: A prospective cohort study.

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.

Total serum IgA levels and HLA-DQB1*02:01 allelic status.

Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and issignificantly associated with Celiac Disease (CD), which recognizes a specific background ofhuman leukocyte antigens (HLA) predisposition (including HLA-DQB1*02:01 allele). A numberof studies investigated the role of HLA in IgAD etiopathogenesis: HLA-DQB1*02 alleles areincluded in the main haplotypes linked to this primary immunodeficiency. In this preliminarystudy, we investigated the potential impact of HLA-DQB1*02:01 allelic status on total serum IgAlevels: 108 serum samples from the bone marrow donors' registry wereanalyzed for total IgA concentration with respect to the HLA-DQB1*02:01 status. Although totalserum IgA levels between HLA-DQB1*02:01 carriers and HLA-DQB1*02:01 negative donorswere not different, we observed a statistically significant difference (p=0.0118) in total serum IgAlevels among donors with low IgA concentration (<80mg/dL) in the sub-analysis between HLA-DQB1*02:01 positive group (including both homozygous and heterozygous carriers) compared toHLA-DQB1*02:01 negative donors. Our results might suggest a role of HLA-DQB1*02:01 allelicvariant in the determination of total serum IgA levels, at least in patients affected with IgAdeficiency and/or otherwise predisposed to it; however, larger and more standardized studies areneeded to confirm this speculation.

#5639 TARGETING BAFF AND APRIL IN IGA-NEPHROPATHY

Abstract Background and Aims B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are critical factors in the differentiation and longevity maintenance of the B-cells pool thereby mediating humoral immunity. BAFF and APRIL are involved in initiating B-cells to become self-reactive and elevated levels of these cytokines are detected in the sera of patients with systemic autoimmune diseases. The aim of the study was to estimate role of APRIL and BAFF in IgA-nephropathy (IgAN) patients and to determine the appropriate IgAN treatment based on the assessment of BAFF and APRIL dynamics in IgAN patients’ sera after 6 months of different treatments. Method The 52 IgAN patients aged 32,0 (27,0; 36,0) y.o., male/female ratio as 34/18 despite using of renin-angiotensin-aldosterone system inhibitors (RAASIs) for 6 months with PU 1,8 (1,0; 1,9) g/day and estimated glomerular filtration rate (eGFR) 78 (61; 103) ml/min were divided into 3 treatment groups: 1 group (n = 20) – 200 mg hydroxychloroquine (HCQ) twice a day, 2 group (n = 20) – received glucocorticoids (GC) regimen Pozzi protocol, 3 group (n = 12) – received (RAASIs) in maximal tolerated dose. The control group included age- and sex-matched healthy donors (n = 10). The number of B-cells in peripheral blood was identified by flow cytometry method. The concentrations of total IgM, IgG, IgA, IgE, APRIL and BAFF were determined by ELISA method using commercial kits. Statistical analysis was done using Statistica 10.0. Results Despite the absence of statistically significant differences in the number of B-lymphocytes the increased levels of total IgM, IgA and IgE (p = 0,001) as well as APRIL (5336 (3574; 5965) pg/ml vs 4543 (4518 ÷ 4755) pg/ml (p = 0,05) and BAFF 378 (191; 541) vs 336 (257; 424) pg/ml (p = 0,07) were established in sera of IgAN patients as compared to control group, respectively. The initial APRIL level was correlated with the degree of tubular atrophy with interstitial fibrosis (R = 0,40, p = 0,05) and serum IgG level (R = 0,35, p = 0,05) in IgAN patients. After 6 months of treatment proteinuria was significantly reduced in HCQ (p = 0,03) and GC (p = 0,02) groups while kidney function was stable in all patients. The dynamic of immunological parameters is presented in the Table 1. It was established that HCQ treatment in IgAN patients decreased the production of IgM (p = 0,01) and IgG (p = 0,02) as well as serum concentration of the APRIL factor (p = 0,05) what correlated with the tendency to eGFR increase (R = –0,46, p = 0,06) as well as with clinical effect of therapy improvement of (R = –0,45, p = 0,04). There were no statistical changes in the level of the BAFF factor in patients with HCQ. After GC treatment a decrease in the synthesis of serum IgA (p = 0,01) as well as trend to decline of B-cells number (p = 0,07) were determined, while in patients treated with RAASIs a significant increase in IgE production (p = 0,05) and tendency in elevation in BAFF levels (p = 0,06) were observed. Conclusion Immunological changes may be the determining factors in the choice of treatment in IgAN patients.

Natural autoimmunity in oligoarticular juvenile idiopathic arthritis

BackgroundOligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive immunity. Considering their major immunoregulatory role in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis.MethodsSeventy children with persistent oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄)2 fragments and the hapten TriNitroPhenol (TNP) as well as the total concentration of serum IgM and IgA were measured by in-house enzyme-immunoassays. Kolmogorov–Smirnov normality test, Kruskal–Wallis H and Mann–Whitney tests were used to assess data distribution, and significant differences of non-parametric data between groups of the study. Backward regression analysis was used to analyze the effect of multiple factors (age, gender, disease activity, anti-nuclear antibody positivity, presence of uveitis) on continuous dependent variables (activities and activity/ concentration ratios of IgM and IgA NAbs).ResultsThe ratios of IgA anti-TNP, anti-actin and anti-F(ab΄)2 levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and of healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed that the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels.ConclusuionsOur findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA.

Study of Colostrum Composition in Lactating Women with Anemia

Background: Colostrum is a pre-milk substance, thick lemon yellow coloured viscous mammary secretion, that is produced immediately after birth, during the first 1-5days of the lactation. Pregnancy induced Anaemia (PIA) is the most common complication of pregnancy in the India. PIA is defined as blood hemoglobin level of less than 11 gm % (WHO). In India, ICMR defines anaemia as hemoglobin less than 10 gm %. it is commonly due to maternal malnutrition resulting in deficiencies of iron, anti anemic factors, folic acid and vitamin B12. Maternal nutritional status has been found to influence the composition of milk, leading to conditions which alters the total proteins, calcium and IgA concentration of the colostrum. Aim and. Objectives: The aim of this study is to compare the composition of following biochemical parameters (total proteins, triglycerides, immunoglobulin A, lactose and calcium) in colostrum of normal pregnancy and pregnancy with anaemia patients, in primigravida, to find out whether there are any significant changes. Materials and Methods: We included a total of 60 lactating women from the postnatal wards of Owaisi hospital /princess Esra hospital, Hyderabad after obtaining their consent. Out of which 30 were Controls (Group A) and 30 lactating anemic women (Group B). Approximately 5ml of colostrum was collected from a single breast within 24 hours of delivery from each subject into sterile storage vials and stored at –20°C and were analyzed within two weeks. The following parameters were analyzed in each sample of colostrum, total proteins, triglycerides, Ig A, lactose and calcium.Statistical Analysis: The data was analysed using SPSS software version 17.0 descriptive results are expressed as mean and SD of various parameters in both the groups. p value less than 0.05 was considered as significant and value above 0.05 was considered as non-significant.Discussion &amp; Conclusion: Colostrum is a dynamic, multi-faceted fluid containing nutrients and bioactive factors needed for infant health and development. Nevertheless, knowledge of human milk composition is increasing, leading to greater understanding of the role of human milk in infant health and development, which can be extremely beneficial for preventive and protective aspects of peadiatrics and neonatology.Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Therefore, neonates who are effected and deprived of essential components of colostrum due to anaemia during pregnancy should be provided with the necessary supplements and protection from infections.

Genetic characteristics of colostrum refractive index and its use as a proxy for the concentration of immunoglobulins in Holstein cattle

BackgroundColostral concentration of immunoglobulins (Ig) is crucial for the passive transfer of antibodies from the cow to the new-born calf. Direct determination of Ig by the gold standard radial immunodiffusion method is demanding in terms of time and costs. For this reason, a refractometer is commonly used at the farm level for an indirect estimation of colostrum quality, which is given as the Ig concentration. In this study, colostrum samples were collected from 548 Italian Holstein cows within 6 h of calving. The refractive index (BRIX, %) of these samples was assessed using a portable optical refractometer, as well as the concentration of total protein, IgG, IgA, and IgM by radial immunodiffusion. A four-trait animal model was used to estimate genetic parameters for BRIX and the different immunoglobulin isotypes. A receiver operating characteristic analysis was carried out to evaluate the BRIX diagnostic accuracy.ResultsColostral BRIX was moderately heritable (0.26) and its genetic and phenotypic correlations with IgG (0.91, 0.78), IgA (0.57, 0.57), and IgM (0.71, 0.61) were all positive and of similar order, although the genetic correlations were generally higher than the phenotypic correlations. Low-quality colostrum samples, defined as those with an IgG concentration lower than 50 g/L, were accurately identified by the refractive index on the BRIX scale, with an area under the curve of 0.90.ConclusionsThe use of a refractometer is recommended on dairy farms to produce a proxy for colostral Ig concentration. BRIX is a useful phenotyping tool that can be used in cattle to improve the quality of colostrum for first feeding of calves through both traditional genetic and genomic strategies. Improving colostrum quality will reduce the incidence of failure of passive transfer of immunity in young stock.

Oesophageal secretions reveal local food-specific antibody responses in eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) is associated with elevated IgG4 in oesophageal tissue and serum. Previously, we showed brush-collected oesophageal secretions of EoE patients contained food antigen-specific antibodies IgA and IgG4. It is unknown whether other food-specific antibodies are present along the surface of the oesophagus in EoE. To identify whether immunoglobulins other than IgG4 and food-specific antibodies are elevated along the oesophageal mucosal surface in oesophageal secretions in EoE patients METHODS: Concentrations of total IgA, IgG1, IgG2, IgG3, IgG4, IgM and IgE were measured in oesophageal secretions from patients with active (n= 19) and inactive EoE (n= 9), and non-EoE controls (n= 10). Food-specific antibodies were measured using beads coupled to protein components from dairy, wheat and egg. Total immunoglobulin and cytokine and chemokine concentrations were measured in serum, saliva and oesophageal secretions of four patients with active EoE. Oesophageal secretions have a unique immune profile. Patients with active EoE had elevated IgG2, IgG4 and IgM concentrations in oesophageal secretions compared to those with inactive EoE. Food-specific IgG1, IgG2, IgG4 and IgM were significantly increased in patients with active EoE compared to inactive EoE and non-EoE patients. Furthermore, active patients with a known dairy trigger display higher dairy-specific IgG1, IgG2, IgG4, IgM, IgA and IgE. There is a distinct localised profile of immunoglobulins and food-specific antibodies found within oesophageal secretions in EoE. These findings expand our knowledge about the currently identified immune responses in EoE and suggest possible roles for multiple immunoglobulins and food-specific antibodies in the pathophysiology of EoE.

Dietary supplementation of sulfur amino acids improves intestinal immunity to Eimeria in broilers treated with anti-interleukin-10 antibody.

Oral antibody to interleukin-10 (anti-IL-10) enhances the intestinal immune defense against Eimeria. The sulfur amino acids methionine and cysteine (M+C) play essential roles in inducing and maintaining protective immune responses during intestinal infections. Hence, increased dietary M+C may support the anti-IL-10-induced intestinal immunity to Eimeria. Broilers (n = 640) were arranged in a 2 × 2 × 2 factorial design with 2 levels of each of the 3 main factors: dietary standardized ileal digestible (SID) M+C levels (0.6% or 0.8%), dietary anti-IL-10 supplementation (with or without), and coccidiosis challenge (control or challenge). Briefly, the broilers were supplied with either 0.6% or 0.8% SID M+C, each with or without anti-IL-10 (300 μg/kg), from d 10 to 21. On d 14, broilers from each diet were gavaged with either PBS or Eimeria. The resulting Eimeria infection induced fecal oocyst shedding and intestinal lesions. Broilers fed 0.8% SID M+C (main effects, P ≤ 0.05) had decreased feed-to-gain ratio, increased duodenum and cecum luminal anti-Eimeria IgA titers, and decreased fecal oocyst counts, when compared to 0.6% SID M+C. The supplementation of anti-IL-10 (main effects, P ≤ 0.05) increased cecum luminal total IgA concentration and decreased cecum lesions. Interactions (P ≤ 0.05) were detected for growth performance and cecum luminal IFN-γ. Briefly, the highest body weight gain and feed intake were reached in PBS-gavaged broilers fed 0.8% SID M+C with no anti-IL-10 and in Eimeria-challenged broilers fed 0.8% SID M+C with anti-IL-10. In Eimeria-infected broilers, anti-IL-10 increased intestinal luminal IFN-γ and body weight gain only at 0.8% SID M+C. Collectively, anti-IL-10 increased intestinal luminal IFN-γ levels, decreased cecum lesions and restored growth only when fed with adequate amounts of sulfur amino acids. Our findings underscore the importance of providing sufficient essential nutrients to support the anti-IL-10 induced immunity against coccidiosis.

Assessment of M-protein quantification using capillary electrophoresis and immunosubtraction-based integration in clinical samples with low M-protein concentrations

ObjectivesQuantification of monoclonal protein (M-protein) by serum protein electrophoresis (SPE) is indispensable for diagnosing and monitoring monoclonal gammopathies. However, quantification of small and beta migrating M-proteins is challenging because of overlapping non-immunoglobulin and/or polyclonal immunoglobulin protein fractions. We compared a new integration method based on immunosubtraction (IS-CE) using capillary zone electrophoresis (CZE) against the routine method, which includes a combination of perpendicular drop (0.4%), corrected perpendicular drop (1%) and tangent skimming (98.5%). Design & methodsThe proposed method of M-protein quantification involves calculating the difference in area under the curve between the SPE and a class-specific IS-CE trace. We analyzed the difference in estimated M-protein concentrations obtained with the new method and routine integration methods using 913 samples. For IgA M-proteins at < 10 g/L, the estimated M-protein concentrations were compared with the total IgA concentration. ResultsThe median M-protein concentration of 913 consecutive samples was 6.2 g/L (IQR 2.1–14.3 g/L). The median and median % difference between the two integration methods was 0.68 g/L (IQR 0.01–1.55 g/L) and 10.9% (IQR 0.18–38.7%), showing a larger estimated M-protein concentration with the new method. More than 25% difference was observed in 38% of the samples and was associated with lower total protein concentration, lower M-protein concentration, IgA and IgM heavy chain isotypes, and beta- or beta-gamma migration. When 161 samples with IgA M-protein < 10 g/L were compared against total IgA concentration, the median bias of the new method was smaller compared to that of the existing method (-0.95 g/L vs. −1.3 g/L, P < 0.0001). ConclusionsThe use of IS based integration using CZE and IS-CE is promising especially for small and beta migrating M-proteins.

Recurrence of IgA nephropathy after kidney transplantation: experience from the Swiss transplant cohort study

BackgroundRecurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in about 30% of patients. The relevance of recurrence for the long-term graft survival is expected to increase, since graft survival continues to improve.MethodsIn a nested study within the Swiss Transplant Cohort Study the incidence of IgAN recurrence, predictive factors, graft function and graft and patient survival were evaluated. Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex were measured using ELISA-based immunologic assays.ResultsBetween May 2008 and December 2016, 28 women and 133 men received their kidney allograft for end-stage kidney disease due to IgAN in Switzerland. Over a median follow-up time of 7 years after transplantation, 43 out of 161 patients (26.7%) developed an IgAN recurrence, of which six (13.9%) had an allograft failure afterwards and further four patients (9.3%) died. During the same follow-up period, 6 out of 118 patients (5%) each experienced allograft failure or died without prior IgAN recurrence. After 11 years the risk for IgAN recurrence was 27.7% (95%-CI: 20.6–35.3%). Renal function was similar in patients with and without recurrence up to 7 years after transplantation, but worsened thereafter in patients with recurrence (eGFR median (interquartile range) at 8 years: 49 ml/min/1.73m2 (29–68) vs. 60 ml/min/1.73m2 (38–78)). Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex within the first year posttransplant showed no significant effect on the recurrence of IgAN. Younger recipients and women had a higher risk of recurrence, but the latter only in the short term.ConclusionsOur study showed a recurrence risk of 28% at 11 years after transplantation, which is consistent with previous literature. However, the predictive value of known biomarkers, such as serum Gd-IgA1 and IgA-IgG IC, for IgAN recurrence could not be confirmed.

Gender dimorphism in IgA subclasses in T2-high asthma

Immunoglobulin A (Chan in J Allergy Clin Immunol 134:1394–14014e4, 2014), the second most abundant immunoglobulin in serum, plays an important role in mucosal homeostasis. In human serum, there are two subclasses of IgA, IgA1 (≅ 90%) and IgA2 (≅ 10%), transcribed from two distinct heavy chain constant regions. This study evaluated the serum concentrations of total IgA, IgA1, and IgA2, and total IgG, IgG1, IgG2, IgG3, and IgG4 in T2-high asthmatics compared to healthy controls and the presence of gender-related variations of immunoglobulins. Total IgA levels were increased in asthmatics compared to controls. Even more marked was the increase in total IgA in male asthmatics compared to healthy male donors. IgA1 were increased only in male, but not in female asthmatics, compared to controls. Concentrations of IgG2, but not IgG1, IgG3, and IgG4, were reduced in asthmatics compared to controls. IgG4 levels were reduced in female compared to male asthmatics. In female asthmatics, IgA and IgA1 levels were increased in postmenopause compared to premenopause. IgA concentrations were augmented in mild, but not severe asthmatics. A positive correlation was found between IgA levels and the age of patients and an inverse correlation between serum concentrations of IgA2 and IgE in asthmatics. A positive correlation between total IgA or IgA2 and IgG2 was found in asthmatics. These results highlight a gender dimorphism in IgA subclasses in male and female T2-high asthmatics. More adequate consideration of immunological gender disparity in asthma may open new opportunities in personalized medicine by optimizing diagnosis and targeted therapy.

Effects of Age and Dietary Factors on the Blood Beta-Hydroxybutyric Acid, Metabolites, Immunoglobulins, and Hormones of Goats.

The study was aimed to examine the effects of age and dietary beta-hydroxybutyric acid (BHBA) on blood BHBA and blood health indicators in goat kids. Thirty male goats of five ages (1, 2, 3, 6, and 12 months old) were selected for blood sampling to determine the influence of age. Another 64 goat kids (half males and half females) were weaned at 1 month old and fed with starter diets with control, low, medium, and high BHBA doses (0, 3, 6, and 9 g/animal/day, respectively). Six goats per treatment were selected for blood analysis at 2 and 3 months of age. There were significant effects (p < 0.01) of ages on the blood parameters of goat kids. The 6- and 12-month-old goats showed significantly lower blood total protein, globulin, BHBA, IgA, and IgM concentrations than did young goats, while they had a higher albumin-to-globulin ratio than young goats. The blood glucose decreased (p < 0.01) and IgG increased over time (p < 0.01). In blood, growth hormone (GH) and insulin-like growth factor I (IGF-I) were lower (p < 0.01) at 1- and 3-month-old goats than 12-month-old goats. The high dietary BHBA improved (p < 0.05) the ratio of albumin to globulin of 2-month-old kids compared with control. The blood GH and IGF-I were lower (p < 0.01) in the medium BHBA dose at 2 months of age than control. These results suggested that age greatly impacted blood composition, especially around weaning, and dietary BHBA showed beneficial regulating effects on blood total protein level in young goats.

The Effects of Exercise on Breastmilk Composition and Supply

ObjectiveThe objective of this brief literature review was to identify and summarize the research on exercise’s effects on breastmilk composition and supply and report the implications of these findings.MethodAn online database search was conducted; sixteen articles met the inclusion criteria and were included within the review.ResultsBreastfeeding mothers were observed to have higher total milk volume, IgA, and lactic acid concentrations after maximal exercising. Exercising does not seem to affect lipid or major micronutrient content in breastmilk. These changes in supply and composition do not seem to affect lactation performance or infant acceptance.ConclusionDue to the limited evidence available, further research needs to be conducted to draw stronger conclusions on how exercise affects breastmilk composition and supply. Research is also warranted to clarify exercise/physical activity guidelines for women who are breastfeeding.

Genome-wide association studies for immunoglobulin concentrations in colostrum and serum in Chinese Holstein

BackgroundThe early death and health problems of calves caused substantial economic losses in the dairy industry. As the immune system of neonates has not been fully developed, the absorption of maternal immunoglobulin (Ig) from colostrum is essential in protecting newborn calves against common disease organisms in their early life. The overwhelming majority of Ig in bovine whey is transported from the serum. Therefore, Ig concentration in the colostrum and serum of dairy cows are critical traits when estimating the potential disease resistance of its offspring.ResultsColostrum, blood, and hair follicle samples were collected from 588 Chinese Holstein cows within 24 h after calving. The concentration of total IgG, IgG1, IgG2, IgA and IgM in both colostrum and serum were detected via ELISA methods. With GCTA software, genome-wide association studies (GWASs) were performed with 91,620 SNPs genotyped by GeneSeek 150 K (140,668 SNPs) chips. As a result, 1, 5, 1 and 29 significant SNPs were detected associated with the concentrations of colostrum IgG1, IgG2, IgA IgM, and serum IgG2 at the genome-wide level (P < 3.08E–6); 11, 2, 13, 2, 12, 8, 2, 27, 1 and 4 SNPs were found significantly associated with total IgG, IgG1, IgG2, IgA and IgM in colostrum and serum at the suggestive level (P < 6.15E–5). Such SNPs located in or proximate to (±1 Mb) 423 genes, which were functionally implicated in biological processes and pathways, such as immune response, B cell activation, inflammatory response and NF-kappaB signaling pathways. By combining the biological functions and the known QTL data for immune traits in bovine, 14 promising candidate functional genes were identified for immunoglobulin concentrations in colostrum and serum in dairy cattle, they were FGFR4, FGFR2, NCF1, IKBKG, SORBS3, IGHV1S18, KIT, PTGS2, BAX, GRB2, TAOK1, ICAM1, TGFB1 and RAC3.ConclusionsIn this study, we identified 14 candidate genes related to concentrations of immunoglobulins in colostrum and serum in dairy cattle by performing GWASs. Our findings provide a groundwork for unraveling the key genes and causal mutations affecting immunoglobulin concentrations in colostrum and important information for genetic improvement of such traits in dairy cattle.

Immunological parameters examination of the oral fluid in normal and pathological conditions: sensitivity analysis of microorganisms in modern therapeutic practice in vitro

Inflammation of the mucosal immune system is a common occurrence (saliva). The masticatory process and salivary enzymes destroy antigenic material that enters the mouth cavity, yet it can still activate immunological responses. Many soluble components are secreted by epithelial cells or incorporated into oral cavity fluids. Defensins, histatins, lysozyme, and lactoferrin all have antibacterial action. They appear to work synergistically with secretory IgA. The objectives of this study is to examine the immunological parameters (concentration of total IgA and secretory IgA) of the oral fluid of the examined individuals in normal and pathological conditions; and to identify the sensitivity/resistance of microorganisms-the main representatives of the oral microflora to antimicrobial drugs widely used in modern therapeutic practice (antibiotics) in vitro. To achieve the study's goals, 65 individuals aged 18 to 50 were evaluated. To measure secretory IgA in oral fluid, we used a solid-phase immunoassay and a ZAO Vector Best sIgA ELISA BEST strip. The "secretory IgA-ELISA" reagent collection is designed to quantify secretory IgA in body fluids using enzyme-linked immunosorbent assay. The enzyme-linked immunosorbent assay measures secretory IgA. The t-test was used to assess the significance of differences across indicator groups. Results indicated that amount of total IgA in oral fluid is significantly lower in people with dental and periodontal problems than in people who are healthy. This indicates a decrease in oral cavity resistance and an increase in carious/periodontal processes. Caries and/or periodontal disease have been linked to lgA deficiency. The results showed that staphylococci and streptococci dominated the oral cavity microbiota in the comparison groups. In addition to this, Neisseria and Veillonella were found. Streptococci accounted for 57 percent of all microorganisms planted in this biotope. Enterobacteria accounted for up to 15%, whereas Neisseria accounted for about 4% and 2%. The decrease in sIgA levels in periodontitis patients' saliva indicates a lack of local mucous membrane protection, increasing the risk of caries and periodontitis. The lower sIgA levels in the mouth make tooth tissue more susceptible to caries-causing microbe adherence than in healthy people.

IgA Vasculitis with Nephritis in Adults: Histological and Clinical Assessment.

Patients with IgA vasculitis (IgAV), an immune complex-mediated disease, may exhibit kidney involvement—IgAV with nephritis (IgAVN). The kidney-biopsy histopathologic features of IgAVN are similar to those of IgA nephropathy, but little is known about histopathologic disease severity based on the interval between purpura onset and diagnostic kidney biopsy. We assessed kidney histopathology and clinical and laboratory data in a cohort of adult patients with IgAVN (n = 110). The cases were grouped based on the interval between the onset of purpura and kidney biopsy: Group 1 (G1, <1 month, n = 14), Group 2 (G2, 1–6 months, n = 58), and Group 3 (G3, >6 months, n = 38). Glomerular leukocytes were more common in G1 than in the other groups (p = 0.0008). The proportion of neutrophils among peripheral-blood leukocytes was the highest in the patients biopsied within a month after onset of purpura (G1: 71 ± 8%). In the patients with an interval >6 months, the neutrophil proportion was lower, 60%. Moreover, the glomerular mesangial proliferation score correlated with the serum total IgA concentration (p = 0.0056). In conclusion, IgAVN patients biopsied <1 month from purpura onset showed an elevated percentage of blood neutrophils and glomerular leukocytes, consistent with an acute-onset inflammatory reaction. In all IgAVN patients, the mesangial proliferation score correlated with the serum IgA level.

Natural Infection of Dairy Cows with Bovine Leukemia Virus Affects Immunoglobulin Levels in Saliva and Serum but Not Milk.

Bovine leukemia virus (BLV) is a retroviral infection that disrupts the immune function of infected animals. It is widespread among U.S. dairy cattle. In this pilot study, the average total IgA and IgM concentrations in milk, saliva, and serum samples from BLV ELISA-positive (ELISA+) dairy cows were compared against samples from BLV ELISA-negative (ELISA−) cows using the Kruskal–Wallis test (with ties). The results from ELISA+ cows were also stratified by lymphocyte count (LC) and proviral load (PVL). In milk and saliva from ELISA+ cows, the average total IgA and IgM concentrations were decreased compared to ELISA− cows, although this was only statistically significant for saliva IgM in cows with low PVL (p = 0.0424). Numerically, the average total IgA concentrations were 33.6% lower in milk and 23.7% lower in saliva, and the average total IgM concentrations were 42.4% lower in milk and 15.5% lower in saliva. No significant differences were observed in the total serum IgA concentrations, regardless of PVL and LC. The total serum IgM from ELISA+ cows was significantly decreased (p = 0.0223), with the largest decreases occurring in the highest PVL and LC subgroups. This pilot study is a first step in investigating the impact of BLV on mucosal immunity and will require further exploration in each of the various stages of disease progression.

Decreased Virus-Neutralizing Antibodies Against Equine Herpesvirus type 1 In Nasal Secretions of Horses After 12-hour Transportation

This study evaluated the effects of 12-hour transportation on immune responses to equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4). Possible replication of EHV-1 and EHV-4 was monitored by real-time PCR of nasal swabs and peripheral blood mononuclear cells (PBMCs), and changes in systemic and mucosal antibodies were investigated. Six healthy Thoroughbreds with transport experience were transported in commercial trucks, repeating the same three-hour route four times. Blood samples for cortisol measurement were taken before departure and every three hours. Nasal swabs, PBMCs, nasal wash and serum samples were collected before departure, at unloading, two and six days after arrival. Cortisol concentration increased significantly after three and six hours of transport (P < 0.05), confirming acute transport stress. However, no evidence of viral replication or lytic infection was observed, and serum virus neutralization (VN) titers for EHV-1 and EHV-4 were unchanged, except for one horse that showed a four-fold decrease in titer against EHV-1 after transportation. Urea and total IgA concentration in nasal washes increased significantly after transportation (P < 0.05), while total IgA/protein ratio was unchanged. A transient, ≥4-fold decrease in VN titers for EHV-1 in nasal wash concentrates was observed in four out of six horses after transportation (geometric mean titer declined from 202 to 57, P < 0.05), suggesting suppression of VN capacity in the nasal mucosa may contribute to susceptibility to EHV-1 after transportation. VN antibodies against EHV-4 in nasal secretion were not detected at any timepoint.