Truncation of the Murine Neonatal Fc Receptor Cytoplasmic Tail Does Not Alter IgG Metabolism or Transport In Vivo.

The neonatal Fc receptor (FcRn) is involved in IgG metabolism and transport in placental mammals. However, whether FcRn is responsible for IgG transfer from maternal serum to colostrum/milk is controversial. Interestingly, large domestic animals, such as cows, pigs, sheep, and horses, in which passive IgG transfer is exclusively completed via colostrum/milk, all express an FcRn α-chain that is shorter in the cytoplasmic tail (CYT) than its counterparts in humans and rodents. To address whether the length variation has any functional significance, we performed in vitro experiments using the Transwell system with the MDCK cell line stably transfected with various FcRn constructs; these clearly suggested that truncation of the CYT tail caused a polar change in IgG transfer. However, we observed no evidence supporting functional changes in IgG in vivo using mice in which the FcRn CYT was precisely truncated. These data suggest that the length variation in FcRn is not functionally associated with passive IgG transfer routes in mammals.

Altered maternal immune networks are associated with adverse child neurodevelopment: Impact of alcohol consumption during pregnancy.

Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a "pathway to pathology". In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-É£, IL-10, TNF-ß, TNF-α, and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.

Effect of maternal pregnancy-induced hypertension on neonatal immunity.

OBJECTIVE: To explore the effect of pregnancy-induced hypertension (PIH) on immune system of neonate. Materials and Methods Sixty neonates whose mothers suffered from PIH were selected and divided into preeclampsia group (n=28) and gestational hyperten sion (GH) group (n=32) according to severity of mother's condition. Thirty neonates having healthy mothers were enrolled as control group. The base clinical characteristics of neonates were collected and umbilical vein blood was drawn to detect the distribution of lymphocyte antigen, immune globulin, and complement level. RESULTS: The gestational week, birth weight, head circumference, and one minute Apgar score of both PIH groups were lower than those of control group, and preeclampsia group was lower than GH group (p < 0.05). There was significant difference between preeclampsia group and control group in blood, routine and blood glucose levels Concerning blood glucose levels, both PIH groups were lower than control group, and preeclampsia group was lower than GH group (p < 0.05). Content of IgG and complement C4 of GH group was lower than those of control group; IgG level of preeclampsia group was also lower than GH group (p < 0.05). CONCLUSIONS: PIH of pregnant mother affects the immunity of neonate, and more severe PIH will more negatively affect immunity of neonate.

The evolutionary dynamics of timing of maternal immunity: evaluating the role of age-specific mortality.

If a female survives an infection, she can transfer antibodies against that particular pathogen to any future offspring she produces. The resulting protection of offspring for a period after their birth is termed maternal immunity. Because infection in newborns is associated with high mortality, the duration of this protection is expected to be under strong selection. Evolutionary modelling structured around a trade-off between fertility and duration of maternal immunity has indicated selection for longer duration of maternal immunity for hosts with longer lifespans. Here, we use a new modelling framework to extend this analysis to consider characteristics of pathogens (and hosts) in further detail. Importantly, given the challenges in characterizing trade-offs linked to immune function empirically, our model makes no assumptions about costs of longer lasting maternal immunity. Rather, a key component of this analysis is variation in mortality over age. We found that the optimal duration of maternal immunity is shaped by the shifting balance of the burden of infection between young and old individuals. As age of infection depends on characteristics of both the host and the pathogen, both affect the evolution of duration of maternal immunity. Our analysis provides additional support for selection for longer duration of maternal immunity in long-lived hosts, even in the absence of explicit costs linked to duration of maternal immunity. Further, the scope of our results provides explanations for exceptions to the general correlation between duration of maternal immunity and lifespan, as we found that both pathogen characteristics and trans-generational effects can lead to important shifts in fitness linked to maternal immunity. Finally, our analysis points to new directions for quantifying the trade-offs that drive the development of the immune system.

Colostrum composition of Santa Inês sheep and passive transfer of immunity to lambs.

This study aimed to analyze the chemical composition and the IgG concentration of the colostrum, transitional milk, and mature milk of Santa Inês ewes as well as the transfer of passive immunity to lambs. Thirty-two pregnant ewes and 38 lambs were used. Ewes were milked immediately after lambing and at 12, 24, 36 h and 10 d postpartum. Colostrum was provided to the lambs at 40±15 min (mean±SE) after birth and then at 30-min intervals for obtaining the intake closest to 10% of body weight, and transitional milk was provided ad libitum. Blood from the lambs was collected 36 h after birth for measuring the serum concentrations of IgG, total protein, albumin, and gamma-globulin. The production was lower in primiparous than in multiparous ewes with body condition score (BCS)<2.75, but did not differ between primiparous and multiparous with BCS≥2.75 (interaction parity and BCS). The IgG concentration and fat, protein, lactose, and defatted dry extract percentages were not affected by the BCS of the ewe at lambing or by the parity. The total solids percentage in the colostrum was higher in ewes with BCS<2.75 (interaction BCS and time). The production and the protein, total solid, and defatted dry extract percentages showed quadratic behavior, the fat percentage decreased linearly, and the lactose percentage increased linearly with time postpartum. The IgG concentration in the colostrum was not correlated with the ewe's weight or BCS at the time of lambing. Moreover, the parity, the BCS, the ewe's type of gestation, and the lamb's sex did not influence the serum concentrations of IgG, total protein, albumin, and gamma-globulin in lambs. Adequate passive immune transfer (PIT) was observed in lambs for which the IgG intake was higher than 30 g. Failure in PIT was observed in 39.5% of lambs when considering a serum IgG concentration lower than 15 mg/mL and in 21% when considering a serum total protein concentration lower than 45 mg/mL. The mean apparent efficiency of absorption was 38.10%, with values between 0.02% and 98.80%. The serum IgG concentration was correlated with the total protein concentration (according to the enzymatic colorimetric method), the gamma-globulin concentration, and the absorption efficiency. The extreme variation on apparent efficiency of absorption may have an effect on the success of PIT. Lambs should consume at least 30 g of IgG in the first 24 h of life to ensure adequate PIT.

Schmallenberg virus antibody persistence in adult cattle after natural infection and decay of maternal antibodies in calves.

BACKGROUND: Schmallenberg virus (SBV) has swept through the major part of Europe in the period 2011-2013. A vaccine against SBV has been developed and may be a possible preventive instrument against infection. Presently, there is no data available to refute the assumption that natural SBV infection results in long-term immunity. In that respect, it is of interest to know how long (protecting) virus-neutralizing antibodies are present in naturally infected animals. New-born calves acquire passive immunity from their dams by ingestion and absorption of antibodies present in colostrum, which can block the production of serum antibodies when vaccine is administered to calves with maternally derived antibodies. In that respect, it is useful to know how long it takes for maternal antibodies against SBV to disappear in young animals born from infected dams. RESULTS: Longitudinal whole-herd serological monitoring using virus neutralization test (VNT) indicated that 80% of adult dairy cows still had measurable antibodies against SBV at least 24 months after the estimated introduction of the virus into the herd. Median 2Log VNT titer of the adult dairy cows (≥1 year) dropped from 8.6 to 5.6 in a period of 17 months. Median 2Log VNT maternal antibodies titers of calves sampled within 30 days after birth was 8. Calves lost their maternally-derived antibodies after 5-6 months. There was a definite positive relationship between the VNT titer of the dam and the VNT titer of the corresponding calf (age ≤ 30 days) of dam-calf combinations sampled on the same day: the higher the VNT titer of the dam, the higher the VNT titer (maternal antibodies) of the calf. CONCLUSIONS: Our field data support the assumption that natural SBV infection in adult cows results in persistence of specific antibodies for at least two years. Based on the observed decay of maternally-derived antibodies in calves, it is presumed safe to vaccinate calves against SBV at an age of approximately 6 months.

Specific and non-specific immunity of piglets from sows fed diets containing specific fatty acids in field conditions.

The transfer of passive immunity from sows to piglets is important and it is the first immune protection of the new born piglet. Improving sows immunity by adding immuno-stimulating product in sows diet can positively affect colostrum composition and transfer of immune molecules to piglets. The aim of the current study is to evaluate the benefit of a different solution, made of specific fatty acids from marine origin that have been used in human medicine for decades, for sows and piglets. Two trials were conducted in commercial farm, involving 240 sows at different periods of the year. Sows were divided in a control group, without supplementation, and a test group, supplemented with the feed additive from the 90th day of gestation to weaning. Sows body condition, piglets viability and growth were recorded. Milk immunoglobulin content was measured, as well as Aujeszky antibodies in sows and piglets blood as marker of specific immunity, and blood bactericidal activity, complement activity and lysozyme as markers of non specific immunity. No effect of the product was observed on piglets zootechnical criteria and specific immunity parameters but significant improvement of piglet non specific immunity, was observed. No difference was observed neither in the piglets blood PRRSV and PCV2 antibodies and viruses nor in Aujeszky antibodies. Blood complement activity seems to be an accurate indicator of immuno-stimulating additive efficiency. Giving alkyl-glycerol fatty acids to sows in late gestation and lactation can improve the passive immunity transfer to piglets.

Maternal immune stimulation during pregnancy affects adaptive immunity in offspring to promote development of TH17 cells.

Behavioral abnormalities in offspring of murine dams that receive immune stimulation with (poly)I:C during pregnancy are well-documented. In this prenatal model, (poly)I:C-induced maternal cytokines, particularly IL-6, appear involved in the etiology of the behavioral abnormalities. While much has been published on the abnormal behaviors of offspring in this model, much less is known about how maternal immune stimulation affects the adaptive immune system of the offspring, and its possible role in the observed pathophysiology. In the present study, pregnant dams were stimulated with (poly)I:C at E12, and 24h later cytokine levels were measured in maternal sera and amniotic fluids. Lymphocytes from offspring were also analyzed for T Helper (TH) cell subsets. The results demonstrate that lymphocytes from offspring of pregnant dams stimulated with (poly)I:C develop into TH17 cells upon in vitro activation. This preferential TH17 cell differentiation occurs in offspring of pregnant dams with an immunological "memory" phenotype, but not in offspring of immunologically "naive" dams. Comparable levels of IL-6 were found in the sera of immune and naïve pregnant dams, however, there was a disparity between levels of IL-6 in maternal sera and amniotic fluids of (poly)I:C-injected dams. In matings between IL-6 KO dams (IL-6-/-) and wild-type males (IL-6+/+) there was no IL-6 in sera from (poly)I:C-injected dams, but there were high levels of IL-6 in their amniotic fluids. Analysis of supernatants of cultured placental cell preparations from these IL-6 KO dams confirmed that the IL-6 was produced from the fetal (IL-6+/-) component, and heterozygous IL-6+/- offspring could also produce IL-6.

Maternal antibody transfer to broiler progeny varies among strains and is affected by grain source and cage density.

Two experiments were conducted to examine the effects of broiler breeder dietary grain source and cage density on maternal antibody (MatAb) transfer to progeny in 2 genetic strains (A and B). Broiler breeders were assigned to 16 litter floor pens and fed either corn- or wheat-based diets. Breeders were administered 4 live vaccines against Newcastle disease virus (NDV). At 23 wk of age, pullets and cocks, which reflected the full BW distribution from each treatment, were moved to a cage breeder house and placed at 1 or 2 hens/cage. Breeders were artificially inseminated at 44 wk (experiment 1) and 52 wk of age (experiment 2). Eggs were collected for 8 d, incubated, and placed in individual pedigree bags at d 19 of incubation. Blood samples from 5 chicks per treatment combination were collected at hatch in both experiments. Spleen and bursa were collected from the same chicks for histomorphometry analyses in experiment 2. In the second experiment, 12 chicks per treatment were placed in cages. Progeny were provided diets based on the same grain (corn or wheat) as their parents. Serum samples were collected at 5, 9, and 13 d of age and analyzed for anti-NDV MatAb. Data were analyzed as a 2 × 2 × 2 factorial design considering strain, dietary grain source, and cage density as main factors. Interaction effects were observed in breeders and progeny. Experiment 1 showed that strain A chicks had lower levels of MatAb when hens were housed at 2 hens/cage rather than 1 hen/cage. The MatAb levels of strain B chickens were not affected by cage density in either experiment. Experiment 2 demonstrated similar effects of cage density on MatAb levels and the area of bursa follicles for both strains. Progeny of breeders fed corn-based diets had smaller spleen white pulp only when hens were housed at 2 hens/cage compared with 1 hen/cage. The results of these experiments suggest that breeder strain and cage-density conditions affected MatAb transfer to progeny and embryo development of spleen and bursa.

Administration of RRR-α-tocopherol to pregnant mares stimulates maternal IgG and IgM production in colostrum and enhances vitamin E and IgM status in foals.

This study assessed the effect of a vitamin E supplement given to pregnant mares on immunoglobulins (Ig) levels in foals. In addition, the fatty acid (FA) content and composition of the mares' milk was assessed. Milk α-tocopherol concentrations were compared between pregnant Danish Warmblood mares (n = 17) given a daily oral supplement of 2500 international units (IU) RRR-α-tocopherol in the last 4 weeks of pregnancy and a group of unsupplemented mares (n = 17) receiving 170-320 IU vitamin E daily originating from the feed. Milk α-tocopherol was higher in supplemented mares (36.7, 12.4 and 9.8 µmol/l respectively) in relation to control mares (13.1, 6.4 and 5.8 µmol/l on days 1, 2 and 3 respectively; p < 0.001). Milk IgG was higher on days 2 and 3 post-partum (PP) in supplemented mares (1.03 and 0.73 mg/ml respectively) in relation to control mares (0.79 and 0.56 mg/ml respectively; p < 0.05). Milk IgM was higher on days 2 and 3 post-partum (PP) in supplemented mares (0.19 and 0.17 mg/ml) in relation to control mares (0.13 and 0.11 mg/ml respectively; p < 0.05). Plasma α-tocopherol in foals was higher from supplemented mares on days 1, 2 and 3 (5.7, 14.8 and 19.2 µmol/l respectively) in relation to foals from control mares (3.6, 6.1 and 7.6 respectively; p < 0.001). Foal plasma IgM was higher from supplemented mares on day 3 (0.50 mg/ml) in relation to foals from control mares (0.32 mg/ml; p < 0.001). The total FA content in milk was highest on day 1 (21.6 g FA/kg milk) in relation to days 2 and 3 (13.6 and 13.5 g FA/kg milk respectively; p < 0.001). In conclusion, a daily oral supplement of 2500 IU RRR-α-tocopherol increased α-tocopherol content in mare milk and foal plasma, IgG and IgM in mare milk and IgM in foal plasma.

Evaluation of passive transfer in captive greater kudu (Tragelaphus strepsiceros).

Failure of passive transfer (FPT) in captive greater kudu (Tragelaphus strepsiceros) calves can lead to increased morbidity and mortality. In this retrospective study, serum samples from neonatal kudu calves were tested for immunoglobulin using different tests validated for domestic ruminants, including measurement of gamma globulin (GG) measured by protein electrophoresis, total solids (TS) measured by calibrated refractometry, total protein (TP) and globulins measured by colorimetry, gamma glutamyltransferase (GGT), and the zinc sulfate turbidity test (ZSTT). In a logistic regression model, TP, TS, globulins, and the natural log transform of GGT were the only significant parameters associated with FPT. Various historic parameters related to the dam, as well as calf weight, sex, glucose, and packed cell volume, were not significant. Based on the results, FPT in greater kudu is defined as GG of < 0.5 g/dl, a value lower than that in domestic cattle. TS measured by refractometry has an 80% sensitivity and a 100% specificity for FPT in greater kudu. With FPT defined as GG < 0.5 g/dl, kudu calves with a TS < 4.8 g/dl and a negative ZSTT have an increased probability of requiring medical intervention and additional diagnostics may be warranted.

Oxidative stress in cows according to calving season: passive calf immunity and its relationship with colostrum quality.

This study details the relationship between maternal plasma oxidant-antioxidant enzymes with colostrum quality, serum gamma glutamyl transferase (GGT), immunoglobulin G (IgG) and IgM concentrations of calves in the different calving seasons. Holstein breed cows between two and eight lactations and their calves were enrolled in the study. Holstein cows calving in winter (n=45) and their calves (n=45) were assigned to the winter group, while cows calving in summer (n=45) and their calves (n=45) were assigned to the summer group. Samples for malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were collected on day -21±3 before expected calving and also on calving day (Day 0). IgG and the specific gravity of the colostrum were determined after calving. Serum GGT and IgG and IgM were measured before the feeding, with colostrum, of calves (0 hours) and also in the 24th hour following the feeding of colostrum. Plasma MDA levels at -21±3 and 0 days in the summer cows were determined to be higher. GSH-Px activity was higher in the winter cows. IgG levels and the specific gravity of the colos- trum were also higher in the winter cows. Calf IgG levels at the 24th hour of life were higher in the winter cows. In the winter group, IgM levels at 0 and 24 hours were also higher. While MDA was negatively correlated with IgG, IgM, GGT, IgG and the specific gravity of colostrum, GSH-Px activity had a positive correlation with IgG, IgM, GGT, IgG and the specific gravity of colostrum. The observed differences in plasma MDA, GSH-Px, calf serum IgG and IgM levels, and colostrum quality between both groups suggest a possible seasonal effect. The relationship between maternal oxidant-antioxidant enzymes, colostrum quality, and passive calf immunity revealed that these enzymes could be used as indicators in the evaluation of calf health and colos- trum quality.

Dietary-dependent trans-generational immune priming in an insect herbivore.

Trans-generational effects on immunity are well known in vertebrates and are considered in many evolutionary and ecological theories of species interaction. Maternal effects have been identified to be of special importance, and are now recognized as a mechanism for adaptive phenotypic response to environmental heterogeneity. We have previously shown that exposure to dietary non-pathogenic bacteria can induce several aspects of immune response in an insect herbivore, the cabbage semilooper (Trichoplusia ni). Here, we test the effects of this exposure on the immune status of the next generation, measuring immune parameters on three different levels-enzyme activities, protein expression and transcript abundance. We also monitored fitness-related traits which are often negatively correlated with increased immunocompetence. We found evidence for trans-generational priming on all these levels, with immune system parameters that are clearly not transmitted in a 1 : 1 ratio from parent to offspring, but rather in a complex manner with a strong but not exclusive maternal component. These findings indicate that trans-generational priming is a complex and multifaceted phenomenon, potentially playing a role as a long-term but non-genetic mode of environmental adaptation.

Maternal transfer of IgE and subsequent development of IgE responses in the horse (Equus callabus).

Immunoglobulin E (IgE) mediates the immune response to parasites, but can also cause allergies. In humans maternal IgE is not transferred to cord blood and high levels of cord blood IgE are associated with subsequent allergy. In horses, both maternal IgG and IgE are transferred via colostrum; the IgE levels in the mare's serum, the colostrum and the foal's serum are correlated but the consequences of IgE transfer to foals are not known. By about 6 weeks of age the levels of IgE in foal serum have dropped to a nadir, at 6 months of age the level of IgE has risen only very slightly and is no longer correlated with the levels seen at birth, IgE(+) B-cells could be detected in lymphoid follicles of some foals at this age. Surprisingly, the levels of total IgE detected in a foals serum at 6 months of age are significantly correlated with the level in its serum at 1, 2 and even 3 years of age suggesting that by 6 months of age the foals are synthesizing IgE and that a pattern of relatively higher or lower total serum IgE has been established. The neonatal intestinal mucosa contained connective tissue mast cells which stained for bound IgE in foals up to 9 weeks of age but not mucosal mast cells, thereafter, the intestinal mast cells were IgE negative until 6 months of age. IgE antibodies to Culicoides nubeculosus salivary antigens were detected in Swiss born foals from imported Icelandic mares allergic to Culicoides spp. yet the foals showed no signs of skin sensitization and such second generation foals are known not to have an increased risk of developing allergy to Culicoides. Overall this evidence suggests there is a minimal effector role of maternal IgE also that maternal IgE has waned prior to the onset of IgE synthesis in foals and does not support maternal priming of IgE responses in foals. Furthermore the total levels of IgE in any given foal are seen to be relatively high or low from soon after the onset of IgE synthesis, and most likely they are determined by genetic factors.

Passive immune transfer in puppies.

The puppy, born without immunoglobulins G (IgG), acquires a passive systemic immunity thanks to colostrum intake during the two first days of life. The quality of passive immune transfer (i.e. blood IgG concentration at two days of age), highly variable between litters and between puppies within litters, depends mainly on the time elapsed between birth and ingestion of colostrum, with limited influence of colostrum IgG concentration. Deficit in passive immune transfer, impacting puppy's health and neonatal mortality rate, can be indirectly diagnosed through blood gammaglutamyltransferases assay and evaluation of growth rate over the two first days of life. In the absence of maternal colostrum, few homo- and heterospecific immune sources are available and canine colostrum banking remains the optimal solution. Whereas passive immune transfer is crucial for survival during the neonatal period, it later interferes with response to vaccination. In addition to systemic passive immune transfer, maternal antibodies (mainly IgA) would provide local (digestive) immunity, ensuring mid-term protection of the puppies' gut together with probably long term training of the digestive immune system.

Diagnostic performance of direct and indirect methods for assessing failure of transfer of passive immunity in dairy calves using latent class analysis.

Accurate diagnosis of failure of transfer of passive immunity (FTPI) in newborn calves is an essential component of dairy farm management plan. Several methods (direct and indirect) are available for diagnosis of FTPI in dairy calves. However, the indirect methods offer an advantage over the direct methods in not requiring an experienced veterinarian, rapid, cost efficient and can be performed under field-setting. The objective of this study was to estimate the diagnostic performance of radial immunodiffusion (RID) assay, transmission infrared (TIR) spectroscopy and digital Brix refractometer for diagnosis of FTPI in dairy calves using latent class models at four cut-off values of digital Brix refractometer. Holstein calves (n = 691) from 40 commercial dairy farms in the four Atlantic Canada provinces were blood-sampled and tested for detection of FTPI. Results showed that the number of calves with FTPI was 253 (36.6%) by RID, 194 (28.1%) by TIR and 204 (29.5%) by Brix refractometer at cut-off value of 8.2%. Estimates of SeRID was higher than SeTIR and SeBrix, at all Brix refractometer cut-offs, but with increase of Brix refractometer cut-off from 8.2 to 8.5%, SeRID and SeTIR were decreased from 96.0% (95% PCI: 88.0-99.0) and 79.0% (95% PCI: 70.0-85.0), to 92.0% (95% PCI: 77.0-99.0) and 74.0% (95% PCI: 61.0-82.0), respectively. SpRID and SpTIR were always higher than SpBrix at all tested cut-offs and were above 92.0%, and 96.0%, respectively. With increasing the cut-off of Brix refractometer from 8.2 to 8.5%, SeBrix estimate has remarkably increased from 79.0% (95% PCI: 70.0-96.0) to 95.0% (95% PCI: 87.0-100.0), respectively. Whilst, SpBrix was decreased from 95.0% (95% PCI: 91.0-98.0) at cut-off 8.2% to 84.0% (95% PCI: 78.0-94.0) at cut-off 8.5%. In conclusion, RID has a higher Se than TIR and Brix, if the latter is used with cut-offs of 8.2% or 8.3%. However, the higher the cut-off, the more comparable sensitivities of RID and digital Brix refractometer. The median estimate of SpTIR was always higher than SpRID and SpBrix at all tested cut-offs. However, the 95% confidence interval estimates of the three tests were overlapping across the tested cut-offs of digital Brix refractometer reflecting the inability to prefer a test over the other based on the Sp estimate.

Usefulness of digital and optical refractometers for the diagnosis of failure of transfer of passive immunity in neonatal foals.

BACKGROUND: Neonatal foals with failure of transfer of passive immunity (FTPI) are at higher risk of morbidity and mortality. Successful treatment of FTPI is time-dependent, thus rapid and accurate measurement of serum IgG concentration is important for the management and care of neonatal foals. OBJECTIVES: To validate the use of digital and optical refractometers for assessing FTPI in neonatal foals and compare the diagnostic performance and level of agreement of the two refractometers to the reference standard radial immunodiffusion (RID) assay. STUDY DESIGN: A retrospective validation study. METHODS: Serum samples (n = 253) were collected from 230 foals admitted to the Veterinary Teaching Hospital and Ambulatory Equine Service between 2012 and 2017. The serum IgG concentrations were measured by the reference RID assay, digital Brix and optical refractometers. The correlation between results of two refractometers and RID assay was assessed. A receiver operating characteristic curve was created and used to identify the optimal cut-offs for evaluating sensitivity and specificity of the two refractometers to detect foals with complete and partial FTPI. RESULTS: The RID-IgG concentrations were positively correlated with the Brix scores obtained from a digital refractometer (r = 0.73, P = 0.001) and serum total protein obtained from an optical refractometer (r = 0.72, P = 0.001). The sensitivity and specificity of the digital Brix refractometer at optimal cut-off (≤7.8% Brix) were 88.1 (95% CI: 74.4-96.0) and 67.7% (95% CI: 60.6-74.3) to detect RID-IgG<4 g/L and 79.0 (95% CI: 68.5-87.3) and 77.3% (95% CI: 69.8-83.8) to detect RID-IgG≤8 g/L, respectively. The sensitivity and specificity of the optical refractometer at optimal cut-off (≤42 g/L) were 86.1 (95% CI: 72.1-94.7) and 70.9% (95% CI: 63.9-77.3) to detect RID-IgG<4 g/L and at cut-off (≤44 g/L) were 82.9 (95% CI: 73.0-90.3) and 72.7% (95% CI: 64.8-79.6) to detect RID-IgG≤8 g/L, respectively. MAIN LIMITATIONS: The number of diseased foals was small to investigate the validity of the selected cut-off values for assessing FTPI in sick foals. CONCLUSIONS: The two refractometers exhibit utility as rapid, inexpensive screening tests and have a good sensitivity for assessing FTPI in neonatal foals.

Cytokines in milk and the role of TGF-beta.

Cytokines are required for normal growth and development of the mammary gland and TGF-ß prominently represents an established effector of apoptosis, e.g., during involution of the mammary gland. By the control of intracellular signaling pathways, including JAK/STAT, MAPK, PI-3K, and NF-κB, cytokines efficiently regulate cell proliferation and inflammation in the breast. Therefore, cytokines are discussed also in a context of malignant mammary growth. As a group of tissue hormones produced by somatic cells or by cells from the immune system, cytokines are defined by their immunomodulatory potential. Over the past 40 years, multiple cytokines were identified in colostrum and milk. Importantly, cytokines derived from mammary secretions after birth are required for maturation of the immune system in the developing gastrointestinal tract from the suckling. Moreover, recent studies have further assessed the particular interactions between probiotic bacterial strains and cytokines. In light of the increasing prevalence of inflammatory diseases of the gastrointestinal system, the effects of probiotic microorganisms during milk fermentation may have immunotherapeutic potential in the future.

Biomarkers and immunoprofiles associated with fetal abnormalities of ZIKV-positive pregnancies.

BACKGROUND: An intricate fetal-maternal immune crosstalk during pregnancy is essential for a healthy birth. Hence, the infection-induced alterations of maternal immunity often lead to adverse outcomes for mother and/or child. The emergence of Zika virus (ZIKV) infection in pregnant women has been associated with more than 3,000 cases of microcephaly and nervous system malformations. METHODS: To explore the potential correlation of ZIKV-induced alteration of maternal immunity with fetal abnormalities, we performed extensive sera immunoprofiling of 74 pregnant women: 30 symptomatic ZIKV+ pregnant patients and 30 healthy pregnant controls in ZIKV-endemic Rio de Janeiro, along with 14 healthy pregnant controls in non-endemic Los Angeles. RESULTS: Extensive multiplexing analysis of 69 cytokines revealed that CXCL10, CCL2, and CCL8 chemokines were specifically associated with symptomatic ZIKV+ infection during pregnancy, and distinct immunoprofiles were detected at different trimesters in ZIKV-infected pregnant women. Intriguingly, the high CCL2 level and its inverse correlation with CD163, TNFRSF1A, and CCL22 levels was apparently associated with ZIKV-induced abnormal birth. CONCLUSION: Our findings provide insights into the alteration of ZIKV-elicited maternal immunity, serving as a potential clinical biomarker platform. FUNDING: NIH (CA200422, CA180779, DE023926, AI073099, AI116585, AI129496, AI140705, AI069120, AI056154, AI078389, AI28697, AI40718 and AI129534-01), Hastings Foundation, Fletcher Jones Foundation, Departamento de Ciência e Tecnologia (DECIT/25000.072811/2016-17) do Ministério da Saúde do Brasil, and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior CAPES/88887.116627/2016-01.

Immune responsiveness in the neonatal period.

The maintenance of pregnancy requires suppression of the maternal immune system which would naturally recognize the developing fetus as an allograft and seek to destroy it by mounting a Th1 regulated cytotoxic immune response. During pregnancy a range of soluble factors are produced by the placenta which switch maternal immune regulation towards a protective Th2 phenotype. These factors also influence the developing fetal immune system and all newborns initially have an immunological milieu skewed towards Th2 immunity. Vaccination during the neonatal period must therefore overcome the dual challenge of the inhibitory effect of maternally derived antibody and this natural Th2 regulatory environment. One means of overcoming these obstacles is by the use of adjuvant systems that can redirect the neonatal immune response towards an appropriate Th1 regulated reaction that affords protection from infectious disease. In this overview, experiments are described in which viral antigens incorporated into immune stimulatory complexes (ISCOMs) are able to induce immune responses with balanced Th1 and Th2 regulation in neonatal mice, as evidenced by the nature of the IgG subclass response and cytokine profile, and the induction of cytotoxic lymphocytes. ISCOM adjuvanted vaccines are able to induce similar protective immunity in the newborn of larger animal species including cattle, horses and dogs.