Immunoglobulin G Concentrations Research Articles

81 Effects of udder quarter location on colostrum yield, nutrients, and immunoglobulin G in beef heifers

Abstract We hypothesized that colostrum total nutrients and immunoglobulin G (IgG) would not be affected by side of the udder, but that they would be greater in the rear versus the front half of the udder due to difference in volume of colostrum produced. Complete colostrum yield was collected individually from each quarter pre-suckling [40.5 ± 21.0 min (SD)] from fall-calving crossbred beef heifers (body weight = 472 ± 34 kg; body condition score (= 5.3 ± 0.4) that were either individually-fed 100% (control; n = 12) or 70% (nutrient restricted; n = 12) of NASEM metabolizable energy and metabolizable protein requirements from d 160 of gestation to calving. Analysis of colostrum lactose, protein, triglycerides, and free glucose was performed using colorimetric assays on a UV-visible light microplate reader. Colostrum IgG was analyzed using a commercially available ELISA kit. Quarter yield, nutrient or IgG concentration, and total nutrients or IgG were analyzed using the mixed procedure of SAS with fixed effects of udder location, nutritional plane, and their interaction in the model. Nutritional plane was not part of the current objective, but was included to account for variation in colostrum yield due to nutrient restriction, as we have previously reported. Separate statistical comparisons were made between the front and rear quarters and between the right and left quarters of the udder, with each quarter considered a sampling unit within each experimental unit (half) for both analyses. The interaction of udder location × nutritional plane did not affect (P ≥ 0.11) any variable. Nutrient restriction decreased (P ≤ 0.03) colostrum yield, total lactose, and total free glucose compared with controls. Front quarters produced less volume (P < 0.001; 36.2% of total); total lactose, protein, and free glucose (P ≤ 0.02; 34.3 to 43.3%); and total IgG (P < 0.001; 33.7%) than rear quarters. Front quarters tended to produce less (P = 0.07; 43.3%) total triglycerides than rear quarters. Lactose concentration was 10.5% greater (P = 0.05) in front compared with rear quarters, but other nutrient or IgG concentrations were not affected (P ≥ 0.18). Udder side did not affect total volume (P = 0.78), total nutrients (P ≥ 0.36), or total IgG (P = 0.79). The left side represented 50.7% of the total volume and 50.1 to 53.4% of total nutrients and IgG produced. Concentration of nutrients and IgG also were not affected (P ≥ 0.31) by udder side. In conclusion, colostrum did not differ between udder sides, but, relative to front quarters, rear quarters produced greater nutrient and IgG yield due to greater colostrum volume with minimal differences in nutrient or IgG concentrations.

PSIII-11 Impacts of late gestational in utero heat stress on small intestine dynamics of neonatal dairy calves

Abstract Late gestation heat stress in dairy cows has been shown to negatively affect offspring growth and development. In utero heat stressed calves have altered small intestine morphology and an impaired ability to absorb colostral immunoglobulin G (IgG). Thus, the objective of this study was to characterize potential cellular and molecular alterations in the small intestine of neonatal in utero heat stressed calves. In the last ~56 d of gestation pregnant dams were either heat stressed (shade; n = 41) or cooled (shade, fans, soakers; n = 41) resulting in heifers that were in utero heat stressed (IUHS, n = 15) or in utero cooled (IUCL, n = 15). Heifers were fed 3.78 L of high-quality colostrum within 2 h of birth. Apparent efficiency of absorption (AEA) of IgG was calculated by measuring IgG content fed in colostrum and in 24 h serum. Within 4.6 ± 2.3 h of birth a subset of calves (n = 8/treatment) not fed colostrum were euthanized to collect samples from the ileum. Tissue for histological analysis was placed in 10% neutral buffered formalin before being dehydrated, embedded in paraffin, cut into 5 μm thicknesses, and mounted to glass slides. The TUNEL method was used to identify apoptotic cells using the Keyence BZ-X800 Microscope. Tissue for gene expression analysis was snap-frozen and kept at -80°C before RNA extraction and cDNA synthesis. The transcript abundance of endosomal (FCGRT, DAB2, MAMDC4), tight junction (ZO1, ZO2, ZO3, OCLN, CLDN1), and heat shock (HSP90, HSF1) related genes were measured by qPCR using the CFX96 Real-Time PCR detection System (BIO-RAD). Data were analyzed using PROC MIXED or PROC GLIMMIX depending on the response variable. TUNEL results are expressed as the proportion of positive cells to total cells. Quantitative PCR data were analyzed by assessing the estimates of the model relative to the geometric mean of 3 reference genes (ACTB, GADPH, RSP9; ΔΔCT). The concentration of colostrum IgG fed to calves was not different (136.1 vs. 122.5 g/L; IUHS vs. IUCL, respectively; P = 0.32), but AEA of IgG was reduced in IUHS relative to IUCL calves (23.5 vs. 33.3%; P < 0.01). The proportion of apoptotic cells within the villi of the ileum was increased in IUHS calves compared with IUCL (2.11 vs. 1.57%; P < 0.01). Ileum gene transcript abundance of DAB2 and MAMDC4 were increased (P < 0.01), while FCGRT transcripts tended to increase in IUHS calves (P = 0.08). All tight junction and heat shock-related gene transcripts were increased within the ileum of IUHS calves (P ≤ 0.02) with the exceptions of CLDN1 and HSP90, which were not different between treatments (P ≥ 0.22).These results suggest that exposure to heat stress in utero impact small intestine integrity after birth and affect key IgG transporters, providing insight into underlying mechanisms responsible for reduced IgG absorption in IUHS calves.

The Effects of Microbial Additive Supplementation on Growth Performance, Blood Metabolites, Fecal Microflora, and Carcass Characteristics of Growing-Finishing Pigs.

This study aimed to assess the effects of microbial additives that produce antimicrobial and digestive enzymes on the growth performance, blood metabolites, fecal microflora, and carcass characteristics of growing-finishing pigs. A total of 180 growing-finishing pigs (Landrace × Yorkshire × Duroc; mixed sex; 14 weeks of age; 58.0 ± 1.00 kg) were then assigned to one of three groups with three repetitions (20 pigs) per treatment for 60 days of adaptation and 7 days of collection. Dietary treatments included 0, 0.5, and 1.0% microbial additives in the basal diet. For growth performance, no significant differences in the initial and final weights were observed among the dietary microbial additive treatments, except for the average daily feed intake, average daily gain, and feed efficiency. In terms of blood metabolites and fecal microflora, immunoglobulin G (IgG), blood urea nitrogen, blood glucose, and fecal lactic acid bacteria count increased linearly, and fecal E. coli counts decreased linearly with increasing levels of microbial additives but not growth hormones and Salmonella. Carcass quality grade was improved by the microbial additive. In addition, carcass characteristics were not influenced by dietary microbial additives. In conclusion, dietary supplementation with 1.0% microbial additive improved average daily gain, feed efficiency, IgG content, and fecal microflora in growing-finishing pigs.

Association between serum IgG concentrations and the incidence of infections in patients with chronic lymphocytic leukemia and secondary immunodeficiency under treatment with Privigen.

To investigate the association between serum immunoglobulin G (IgG) concentrations and the incidence of infections in patients with chronic lymphocytic leukemia (CLL) and secondary immunodeficiency receiving treatment with Privigen. Data was analyzed from a non-interventional study conducted in 31 centers in Germany and 1 in Austria. Adult CLL patients with hypogammaglobulinemia and recurrent infections were allowed to enter the study upon signing informed consent, if a prior decision for treatment with Privigen had been made. All infections requiring an antimicrobial treatment were subject to analysis. Patients were stratified according to their mean post-baseline serum IgG trough levels in a group with lower IgG trough levels (≤ 5.0 g/L), and a group with higher IgG trough levels (> 5.0 g/L). Overall, 89 patients and 840 treatment cycles were analyzed. Up to 11 treatment cycles (average duration 29 days) were documented in each patient. In the group with higher IgG trough levels (> 5.0 g/L, N = 72), significantly fewer infections were observed than in the group with lower IgG trough levels (≤ 5.0 g/L, N = 17), including fewer severe and serious infections. The Privigen dosage was a major determinant of the post-baseline serum IgG levels. Overall tolerability of Privigen was assessed as very good or good in 91% of patients. This analysis confirms the association of serum IgG trough levels with the incidence of infections and highlights the importance of careful monitoring of IgG levels during treatment of secondary immunodeficiencies in CLL patients.

Evaluation of serum concentrations of total protein and gamma-globulin as an indicator of serum immunoglobulin G concentration in dairy calves

The aim of this study was to evaluate precision of estimating serum immunoglobulin G (IgG) concentration from total protein (TP) or gamma-globulin (γGLB) concentration as an alternative approach, and to compare morbidity of pre-weaned dairy calves differing in serum γGLB concentration. In trial 1, blood was sampled from 129 Holstein calves in the first week after birth, and serum concentrations of TP, γGLB, and IgG were measured. Spearman's correlation coefficient (rs) between serum IgG and TP concentrations was 0.89, and rs between serum IgG and γGLB concentrations was 0.96. Absolute residual (observed – predicted) serum IgG concentrations were smaller when estimated by serum γGLB concentration than by serum TP concentration, and differences in the absolute residuals were smaller for calves fed colostrum replacer (1.68 vs. 4.29 g/L) than those fed whole colostrum (2.41 vs. 3.48 g/L). In trial 2, blood was sampled from 740 Holstein heifer calves during the first week of age, and serum γGLB concentration was measured. The calves were divided into 4 categories based on their serum γGLB concentration; ≥ 1.0 g/dL (Excellent), 0.7 ≤ γGLB <1.0 g/dL (Good), 0.4 ≤ γGLB <0.7 g/dL (Fair) and <0.4 g/dL (Poor). Morbidity for diarrhea and respiratory disease in pre-weaned dairy calves was determined for the first 28 and 56 d of age, and compared among the 4 categories based on serum γGLB concentration. Calves with serum γGLB concentration higher than 0.7 g/dL (Good and Excellent) had less diarrhea during the first 28 d of age than those with lower serum γGLB concentration (Fair and Poor). Calves with serum γGLB concentration higher than 1.0 g/dL (Excellent) had less respiratory diseases for the first 56 d of age than those with lower serum γGLB concentration (Good, Fair, and Poor). These results suggest that serum IgG concentration can be estimated more precisely from concentration of γGLB than TP particularly for calves fed colostrum replacer, and that γGLB concentrations in the first week of age are associated with morbidity of calves. Transfer of passive immunity in dairy calves can be assessed effectively by serum γGLB concentration.

Lot-to-lot immunogenicity consistency of the respiratory syncytial virus prefusion F protein vaccine in older adults

BackgroundPrevious phase 3 studies showed that the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) is well tolerated and efficacious in preventing RSV-associated lower respiratory tract disease in adults ≥ 60 years of age. This study evaluated lot-to-lot immunogenicity consistency, reactogenicity, and safety of three RSVPreF3 OA lots. MethodsThis phase 3, multicenter, double-blind study randomized (1:1:1) participants ≥ 60 years of age to receive one of three RSVPreF3 OA lots. Serum RSVPreF3-binding immunoglobulin G (IgG) concentration was assessed at baseline and 30 days post-vaccination. Lot-to-lot consistency was demonstrated if the two-sided 95 % confidence intervals (CIs) of the RSVPreF3-binding IgG geometric mean concentration (GMC) ratios between each lot pair at 30 days post-vaccination were within 0.67 and 1.50. Solicited adverse events (AEs) within four days, unsolicited AEs within 30 days, and serious AEs (SAEs) and potential immune-mediated diseases within six months post-vaccination were recorded. ResultsA total of 757 participants received RSVPreF3 OA, of whom 708 were included in the per-protocol set (234, 237, and 237 participants for each lot). Lot-to-lot consistency was demonstrated: GMC ratios were 1.06 (95 % CI: 0.94–1.21), 0.92 (0.81–1.04), and 0.87 (0.77–0.99) between the lot pairs (lot 1/2; 1/3; 2/3). For the three lots, the RSVPreF3-binding IgG concentration increased 11.84-, 11.29-, and 12.46-fold post-vaccination compared to baseline. The reporting rates of solicited and unsolicited AEs, SAEs, and potential immune-mediated diseases were balanced between lots. Twenty-one participants reported SAEs; one of these–a case of atrial fibrillation–was considered by the investigator as vaccine-related. SAEs with a fatal outcome were reported for four participants; none of which were considered by the investigator as vaccine-related. ConclusionThis study demonstrated lot-to-lot immunogenicity consistency of three RSVPreF3 OA vaccine lots and indicated that the vaccine had an acceptable safety profile.ClinicalTrials.gov: NCT05059301.

A Phase Three Study of the Safety and Immunogenicity of a Four-dose Series of 20-valent Pneumococcal Conjugate Vaccine in Healthy Infants.

The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions. Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13. A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.

Beyond Birth: Pioneering Insights into Colostrum Quality Variation among Bitches with Different Types of Parturition.

This study deals with the immunological quality of canine colostrum in relation to the different parturition modes in bitches. It included four groups of bitches, who underwent vaginal parturition (VP), emergency cesarean section (EM-CS), elective cesarean section (EL-CS), or elective cesarean section with aglepristone injection 24 h prior to surgery (EL-A). Colostrum samples from 40 bitches of 18 breeds were taken immediately after the birth of the first puppy or directly after surgery, and four hours later. The concentrations of immunoglobulin G (IgG) and IgA were measured using ELISA tests. The initial IgG concentration was 18.3 ± 10.2 g/L, and the IgA concentration was 13.7 ± 5.8 g/L, respectively. Significantly lower IgG and IgA concentrations were observed in the EL-CS group compared to other groups. The administration of aglepristone led to an increase in IgG and IgA concentrations. Despite the lower immunoglobulin levels with EL-CS, the survival rate of the puppies was not affected. The study shows that immunoglobulin concentrations in colostrum vary between bitches, with the type of birth significantly influencing the levels. Progesterone withdrawal before birth could play a decisive role in increasing IgG and IgA concentrations in the mammary glands of the bitches.

An engineered immunomodulatory IgG1 Fc suppresses autoimmune inflammation through pathways shared with i.v. immunoglobulin.

Immunoglobulin G (IgG) antibodies in the form of high-dose intravenous immunoglobulin (IVIG) exert immunomodulatory activity and are used in this capacity to treat inflammatory and autoimmune diseases. Reductionist approaches have revealed that terminal sialylation of the single asparagine-linked (N-linked) glycan at position 297 of the IgG1 Fc bestows antiinflammatory activity, which can be recapitulated by introduction of an F241A point mutation in the IgG1 Fc (FcF241A). Here, we examined the antiinflammatory activity of CHO-K1 cell-produced FcF241A in vivo in models of autoimmune inflammation and found it to be independent of sialylation. Intriguingly, sialylation markedly improved the half-life and bioavailability of FcF241A via impaired interaction with the asialoglycoprotein receptor ASGPR. Further, FcF241A suppressed inflammation through the same molecular pathways as IVIG and sialylated IgG1 Fc and required the C-type lectin SIGN-R1 in vivo. This contrasted with FcAbdeg (efgartigimod), an engineered IgG1 Fc with enhanced neonatal Fc receptor (FcRn) binding, which reduced total serum IgG concentrations, independent of SIGN-R1. When coadministered, FcF241A and FcAbdeg exhibited combinatorial antiinflammatory activity. Together, these results demonstrated that the antiinflammatory activity of FcF241A requires SIGN-R1, similarly to that of high-dose IVIG and sialylated IgG1, and can be used in combination with other antiinflammatory therapeutics that rely on divergent pathways, including FcAbdeg.

Intramammary administration of lipopolysaccharides at parturition enhances immunoglobulin concentration in goat colostrum

In newborn ruminants, transfer of passive immunity is essential to obtain protection against pathogens. This study aimed to increase the permeability of the blood-milk barrier using intramammary lipopolysaccharides (LPS) in goats at parturition to modulate colostrum composition. Twenty multiparous Majorera dairy goats were randomly allocated in one of the two experimental groups. The LPS group (n = 10) received an intramammary administration (IA) of saline (2 mL) containing 50 µg of LPS from Escherichia coli (O55:B5) in each half udder at parturition. The control group (n = 10) received an IA of saline (2 mL). Rectal temperature (RT) was recorded, and a blood sample was collected at parturition (before IA). In addition, RT was measured, and blood and colostrum/milk samples were collected on day (d) 0.125 (3 hours), 0.5 (12 hours), 1, 2, 4, 7, 15 and 30 relative to the IA. Goat plasma immunoglobulin G (IgG) and M (IgM) and serum β-hydroxybutyrate, glucose, calcium, free fatty acids, lactate dehydrogenase and total protein concentrations were determined. Colostrum and milk yields as well as chemical composition, somatic cell count (SCC), IgG and IgM concentrations were measured. The MIXED procedure (SAS 9.4) was used, and the model included the IA, time, and the interaction between both fixed effects. Statistical significance was set as P < 0.05. Goats from the LPS group showed higher RT on d 0.125, 0.5 and 4 relative to the IA compared to the control group (PIA×Time = 0.007). Goat serum biochemical variables and plasma IgG and IgM concentrations were not affected by the IA. Colostrum and milk yield as well as chemical composition were not affected by the IA, except for milk lactose percentage that was lower in the LPS group compared to the control group (4.3 ± 0.08 and 4.6 ± 0.08%, respectively PIA = 0.026). Colostrum SCC was higher in the LPS group than in the control group (3.5 ± 0.09 and 3.1 ± 0.09 cells × 106/mL, respectively; PIA = 0.011). Similarly, milk SCC increased in the LPS group compared to the control group (PIA = 0.004). The LPS group showed higher IgG (PIA = 0.044) and IgM (PIA = 0.037) concentrations on colostrum than the control group (31.9 ± 4.8 and 19.0 ± 4.8 mg/mL, 0.8 ± 0.08 and 0.5 ± 0.08 mg/mL, respectively). No differences in milk IgG and IgM concentrations between groups were observed. In conclusion, the IA of LPS at parturition increases RT, SCC and IgG and IgM concentrations in colostrum without affecting either yield or chemical composition.

Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci

Streptococcus pneumoniae (pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. This study characterises the immunoglobulin G (IgG) repertoire recognising pneumococci from birth to 24 months old (mo) in a prospectively-sampled cohort of 63 children using a panproteome array. IgG levels are highest at birth, due to transplacental transmission of maternal antibodies. The subsequent emergence of responses to individual antigens exhibit distinct kinetics across the cohort. Stable differences in the strength of individuals’ responses, correlating with maternal IgG concentrations, are established by 6 mo. By 12 mo, children develop unique antibody profiles that are boosted by re-exposure. However, some proteins only stimulate substantial responses in adults. Integrating genomic data on nasopharyngeal colonisation demonstrates rare pneumococcal antigens can elicit strong IgG levels post-exposure. Quantifying such responses to the diverse core loci (DCL) proteins is complicated by cross-immunity between variants. In particular, the conserved N terminus of DCL protein zinc metalloprotease B provokes the strongest early IgG responses. DCL proteins’ ability to inhibit mucosal immunity likely explains continued pneumococcal carriage despite hosts’ polyvalent antibody repertoire. Yet higher IgG levels are associated with reduced incidence, and severity, of pneumonia, demonstrating the importance of the heterogeneity in response strength and kinetics across antigens and individuals.

Population pharmacokinetics of immunoglobulin G after intravenous, subcutaneous, or hyaluronidase-facilitated subcutaneous administration in immunoglobulin-naive patients with primary immunodeficiencies

Immunoglobulin G (IgG) replacement therapy is the standard of care for patients with primary immunodeficiencies with antibody deficiencies. Intravenous (IVIG), subcutaneous (SCIG), and hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) therapies differ in their pharmacokinetic (PK) profiles, administration routes, and dosing regimens. Information on use of subcutaneous therapy in IgG treatment-naive patients is limited. This study used population pharmacokinetic (popPK) model-based simulations to characterize IgG PKs in IgG-naive patients with varying disease severity across several IVIG, SCIG, and fSCIG dosing regimens. An integrated popPK model, developed and validated using data from eight clinical trials, was utilized to simulate scenarios that varied by therapy, loading regimen, maintenance dose (equivalent to 400, 600, or 800 mg/kg every 4 weeks [Q4W]), and baseline endogenous total IgG concentration (1.5 or 4.0 g/L). Simulations were performed for age groups of 2–<6, 6–<12, 12–<18, and ≥18 years. Steady-state serum trough IgG concentrations (Cmin,ss), proportion of patients achieving Cmin,ss ≥ 7 g/L, and days taken to reach this threshold were summarized. SCIG provided greater mean Cmin,ss values than IVIG and fSCIG for any scenario. Across all therapies, Cmin,ss tended to increase with age, dose, and endogenous concentration. Although the findings are model-based and not a summarization of real-world observations, doses ≥ 800 mg/kg Q4W with corresponding loading regimens are likely to be clinically appropriate for achieving target IgG concentrations in treatment-naive patients in a timely manner, especially at low endogenous starting concentrations. Therapy-specific dose adjustment based on baseline endogenous IgG concentration, clinical status, and patient characteristics may be warranted.

Effect of bovine colostrum liposomes on the bioavailability of immunoglobulin G and their immunoregulatory function in immunosuppressed BALB/c mice.

Bovine colostrum (BC) has high nutritional value; however, the low bioavailability of immune active substances in BC may affect their immunoregulatory function. Our previous studies indicated that encapsulating bovine colostrum with liposomes could enable the sustained release of immunoglobulin G in vitro; however, the effect of bovine colostrum liposomes (BCLs) on the bioavailability of immunoglobulins in vivo is still unknown. In addition, the immunoregulatory function of BCLs on immunosuppressed mice is still unclear. Therefore, our current study aimed to explore the effect of BCLs on the bioavailability of immunoglobulins, and further explore their immunoregulatory effect on immunosuppressed BALB/c mice. Through metabolic cage experiments, it was shown that BCLs decreased the urine and fecal concentrations of IgG and exhibited a higher bioavailability of IgG in mice than BC (about 2-fold). In addition, by establishing an immunosuppressed animal model, it was found that BCLs could increase the body weight, spleen weight, and thymus weight in immunosuppressed BALB/c mice, which further restored the serum levels of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Through histology analysis, it was suggested that BCLs restored the structure of jejunal epithelial cells, which was accompanied by an improvement in intestinal cytokine levels (IL-4, IL-10, TNF-α, and IFN-γ). Finally, BCLs increased serum and intestine concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in immunosuppressed BALB/c mice, which further indicated that BCLs had a sustained-release effect for immunoglobulin G in vivo. Our current research will provide a basis for understanding the role of BCLs on the bioavailability of IgG and their immunoregulatory effect on immunosuppressed mice, which might further provide some reference for the application of BCLs.

Determination of minimum individual cow colostral immunoglobulin G concentration required to provide adequate total immunoglobulin G mass in pooled colostrum fed to Jersey calves.

Quantify the minimum individual cow colostral immunoglobulin G (IgG) concentration required for pooling to achieve adequate transfer of passive immunity in calves. 201 Jersey cows. Colostrum was collected from 28 pools and heat treated before being fed to calves or stored. Parity, total number of cows contributing to the pool, individual cow colostral volume contributions, and total volume of each colostrum pool were recorded. Colostrum IgG concentrations in individual and pooled (pre- and post-heat treatment) samples were analyzed by radial immunodiffusion and Brix refractometry. Colostral IgG concentration of ≥ 50g/L was considered the current recommended dairy industry standard for acceptable colostrum quality. Multivariable models were performed to determine factors affecting pooled colostral IgG concentrations. The minimum colostral IgG concentration required for pooling to achieve the recommended total mass of at least 200g IgG to be fed to a calf was calculated. Total pool volume and the number of cows contributing to the pool were significant factors affecting IgG concentration. Colostrum pools from ≤ 7 cows, with a minimum pool IgG concentration of 70.4 g/L (22.9% Brix) or colostrum pool volume ≤ 40 L, with a minimum pool IgG concentration of 66.2 g/L (21.8% Brix) achieved the recommended total mass of at least 200g IgG in 4L of colostrum. When feeding pooled colostrum, IgG concentrations higher than the industry standard of 50 g/L is recommended to reduce the risk of failure of transfer of passive immunity in calves.

Difructose Anhydride and Passive Immunity Effects on Passive Immune Transfer and Performance of Feeding Difructose Anhydride to Neonatal Calves.

The objective of this study was to assess the potential effects of supplementing difructose anyhdride III (DFAIII) during the first days of life on the absorption of immunoglobulin G (IgG) and growth performance of calves early in life fed colostrum with a high IgG concentration. Sixty-six healthy new-born Holstein calves were randomly assigned to three treatments consisting of no supplementation (control), supplementation of 12 g/d (DFA12), or 36 g/d (DFA36) of DFAIII during the first 7 d of life via colostrum and milk replacer (MR). Calves were separated from dams at birth and bottle-fed colostrum in two meals, each targeting 2.5 L within the first 18 h of birth. Colostrum had been previously collected from other dams (and preserved frozen) within the first 2 h of calving and had a Brix value ≥32%. Daily consumption of starter concentrate and MR (and colostrum on the first day) were individually monitored. Calves were body weighed using an electronic scale at birth and on a weekly basis thereafter until the end of study at 42 d of age. A sample of colostrum fed to each calf and a blood sample from the jugular vein of the calves were collected at 12 and 24 h of life to determine the IgG concentration. The mean colostrum IgG concentration fed in the current study was 110 ± 33.7 g/L (mean ± SD). No differences in animal performance were found among the treatments. Calves on all treatments consumed the same amount of colostrum with a similar concentration of IgG, and thus the amount of IgG consumed was also similar. Serum IgG concentrations were greater at 24 than at 12 h but did not differ among treatments. However, the apparent efficiency of absorption of colostral immunoglobulins was greater in DFA12 and DFA36 at 12 h of life than in control calves, with no differences observed at 24 h. Even when feeding high-quality colostrum, in terms of IgG concentration, supplementation with difructose anhydride III may pose an additional advantage in promoting the passive transfer of immunoglobulins in neonatal Holstein calves during the first 12 h of life.

An Optofluidic System for Monitoring Fluorescently Activated Protein Biomarkers

AbstractThe ability to monitor protein biomarkers at clinically relevant concentrations is a powerful approach that provides insights into health status. The synergistic combination of microfluidics and photonics (optofluidic) has emerged as a new means to achieve this capability for detection and manipulation of biological samples. Here in this work, we demonstrate an optofluidic device which integrates the detection and the particle‐focusing components to facilitate on‐chip measurement of protein levels. With this design, we use a laser‐induced fluorescence technique for the direct measurement of protein levels on magnetic bead complexes tagged with fluorescein isothiocyanate (FITC) fluorophore. The developed system was employed for the detection of human immunoglobulin G (IgG) as a model protein within a range of 0–20 μg/mL, showing an ability to resolve the fluorescence signal from different IgG concentrations down to 5.4 nM (0.81 μg/mL). The selectivity in detecting specific IgG target was tested by comparing the fluorescence signal levels from other interfering proteins such as bovine serum albumin (BSA) and human IgM. Although our system was designed for detecting IgG protein, this optofluidic device can be a powerful platform for the rapid detection of a diverse range of biomarkers, including viral pathogens retaining adequate signal sensitivity and selectivity.

Effect of glutamine on the systemic innate immune response in broiler chickens challenged with Salmonella pullorum

BackgroundThe objective of this study was to evaluate the effects of glutamine on the growth performance and systemic innate immune response in broiler chickens challenged with Salmonella pullorum. A total of 600 one-day-old Arbor Acres broiler chickens were assigned randomly to 6 dietary treatments with 10 replicates for a 21-day feeding experiment. The experimental treatments were as follows: the control treatment (birds fed the basal diet), the Gln1 treatment, and the Gln 2 treatment (birds fed the basal diet supplemented with 0.5%, and 1.0% Glutamine, respectively). At 3 d of age, half of the birds from each treatment were challenged oral gavage with 2.0 × 104 CFU/mL of S. pullorum suspension (1.0 mL per bird) or an equivalent amount of sterile saline alone, which served as a control.ResultsThe results showed that S. pullorum infection had adverse effects on the average daily feed intake, average daily gain, and feed conversion ratio of broiler chickens compared with those of the CON treatment on d 7, decreased the spleen and bursa of fabricius relative weights (except on d 21), serum immunoglobulin A (IgA),immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations, and spleen melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology gene 2 (LGP2) mRNA expression levels, and increased the mRNA expression levels of spleen Nodinitib-1 (NOD1), Toll-like receptors 2,4 (TLR2, TLR4), DNA-dependent activator of IFN-regulatory factors (DAI), mitochondrial antiviral-signaling protein (MAVS), P50, P65, and RelB on d 4, 7, 14, and 21.Supplementation with Gln improved the relative weights of the spleen and bursa of Fabricius (except on d 21), increased the serum IgA, IgG, and IgM concentrations and the mRNA expression levels of spleen MDA5 and LGP2, and decreased the mRNA expression levels of spleen NOD1, TLR2, TLR4, DAI, MAVS, P50, P65, and RelB of S. pullorum-challenged broiler chickens.ConclusionThese results indicate that Gln might stimulate the systemic innate immune responses of the spleen in broiler chickens challenged with S. pullorum.

Association between TORCH infection and lupus anticoagulant antibody in pregnant women with recurrent abortion.

Abortion is a medical condition that describes pregnancy loss due to various causes including TORCH infections (toxoplasmosis, others (syphilis and hepatitis B), rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV) infection). TORCH infections may pass to the fetus that has low immunity to fight the disease, besides; the complications are much higher during the early stages of pregnancy which may involve abortion. Therefore, investigating the possible factors that could be associated with TORCH infection including the clotting factor lupus anticoagulant antibody is vital. In this study, TORCH antibodies in 33 pregnant women were assessed and then lupus anticoagulant antibodies were tested using Diagnostica Stago STart 4 Hemostasis Analyzer. The serum concentration of immunoglobulin M (IgM) and immunoglobulin G (IgG) for toxoplasma, rubella and CMV were quantitatively determined with Cobas e411. The serum concentration of IgG for rubella and CMV increased in the blood were 90.9% and 66.6% of pregnant women respectively, while toxoplasma results showed an increasing level of IgG in 24.4% of patients. IgM levels for toxoplasma, rubella and CMV are elevated in 6.1%, 3.03% and 24.2% of patients respectively. Lupus anticoagulant antibody is increased in the blood of 72.7% of pregnant women. It was concluded that only rubella and CMV infections cause the increase of lupus anticoagulant antibodies in the tested pregnant women, not toxoplasmosis.

Associations of serostatus upon arrival with clinical respiratory disease, lung consolidation and growth in veal calves

Respiratory tract infections remain a major problem during calf rearing, especially among milk (formula) fed veal. Preconditioning of calves through appropriate colostrum management and vaccination could be helpful to address this issue. The objective of this study was to investigate whether the presence of serum antibodies against major respiratory tract pathogens (Bovine Respiratory Syncytial virus, Parainfluenza 3 virus, Bovine coronavirus, Mycoplasmopsis bovis, Histophilus somni, Pasteurella multocida and Mannheimia haemolytica) and total serum immunoglobulin G (IgG) concentration in calves upon arrival at the veal facility were associated with the occurrence of clinical bovine respiratory disease (BRD) or lung consolidation in the first 3 weeks, as assessed by both the Wisconsin BRD scorecard (based on 5 clinical signs: cough, rectal temperature, ear position, nasal-and ocular discharge) and by quick thoracic ultrasound scanning (qTUS). Additionally, the association between calves' serostatus production parameters were explored. A prospective cohort study was conducted among 442 male dairy calves on a large veal calf facility in Belgium. Both clinical scoring and qTUS were performed on all calves at 4 key moments in the production cycle: arrival at the facility, initiation of first metaphylactic antimicrobial treatment at peak incidence of BRD (wk 1), end of the first metaphylactic treatment (short-term evaluation) and at wk 10 (long-term evaluation). Mixed effects logit regression models were fitted to quantify relationships. The outcomes of interest were clinical respiratory disease (Wisconsin BRD scorecard positive), lung consolidation (≥1cm or ≥ 3cm), average daily weight gain and cold carcass weight. In the first week of production, incidence of lung consolidation (≥1cm) quickly increased from 14.9% upon arrival to 43.0% at the peak of the BRD incidence, while clinical BRD increased from 3.6% to 16.1%. The main finding of this study was that calves who were seropositive for bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV) at arrival had reduced odds of developing lung consolidation at the peak of the outbreak, 0.58 OR (95% CI: 0.38 - 0.89) and 0.37 OR (95% CI: 0.20 - 0.69), respectively. No relationships between serum IgG concentration at arrival and the development of lung consolidations or clinical respiratory disease were found. Nevertheless, on average, throughout the first 10 weeks of the fattening cycle, calves with failed transfer of passive immunity (FPT, serum IgG < 7.5 g/L) gained 40 g/day (95% CI: 10-70g/day) less weight (ADG). Hence, ensuring that calves have a positive serostatus for these respiratory tract pathogens before entering the facility may help lower the incidence of lung consolidations, subsequently reducing treatment incidence and the adverse effects on primary economic outcomes.

Immunomodulation of Antibody Glycosylation through the Placental Transfer

Establishing an immune balance between the mother and fetus during gestation is crucial, with the placenta acting as the epicenter of immune tolerance. The placental transfer of antibodies, mainly immunoglobulin G (IgG), is critical in protecting the developing fetus from infections. This review looks at how immunomodulation of antibody glycosylation occurs during placental transfer and how it affects fetal health. The passage of maternal IgG antibodies through the placental layers, including the syncytiotrophoblast, stroma, and fetal endothelium, is discussed. The effect of IgG subclass, glycosylation, concentration, maternal infections, and antigen specificity on antibody transfer efficiency is investigated. FcRn-mediated IgG transport, influenced by pH-dependent binding, is essential for placental transfer. Additionally, this review delves into the impact of glycosylation patterns on antibody functionality, considering both protective and pathological effects. Factors affecting the transfer of protective antibodies, such as maternal vaccination, are discussed along with reducing harmful antibodies. This in-depth examination of placental antibody transfer and glycosylation provides insights into improving neonatal immunity and mitigating the effects of maternal autoimmune and alloimmune conditions.