Serum IgG Concentrations Research Articles

P-1972. SARS-CoV-2 Vaccine–Induced IgG4 Response Negatively Correlates with Neutralizing Antibodies and Fc Effector Functions

Abstract Background IgG4, the least abundant human IgG subtype, increases after repetitive exposure to some antigens, and may induce immune tolerance. Studies have found that repeat mRNA SARS-CoV-2 vaccination leads to large proportional increases in spike (S)-specific IgG4. By contrast, increased IgG4 has not been observed following repeat vaccination with recombinant SARS-CoV-2 S (rS) protein (NVX-CoV2373, Novavax). Whether vaccine-induced anti-S IgG4 might impair SARS-CoV-2 immunity remains unknown.Figure:Serum anti-Spike IgG1 (A), IgG3 (B), and IgG4 (C) concentrations (ng/mL) measured by ELISA were correlated with neutralizing antibody titers (MN50) measured by infectious virus microneutralization assay. Methods Sera were collected from study participants in 2019nCoV-307 (NCT05463068) and 2019nCoV-301 (NCT04611802), including 2 groups from 2019nCoV-307 who received 3 homologous mRNA doses followed by 1 NVX-CoV2373 dose (mRNA-1273, Moderna, n=10; or BNT162b2, Pfizer, n=10), and a 3rd group from 2019nCoV-301 who received 4 homologous NVX-CoV2373 doses (n=18). Sera collected ≥6 months after the last dose in the first 2 groups and ∼4 weeks after the last dose in the 3rd group were assessed for neutralizing antibodies (nAb), IgG subclass profiles (anti-S total IgG, IgG1, IgG2, IgG3, and IgG4), and Fc effector activities (cell-based ADCP assay; surrogate ADCC by FcγRIIIa binding; and ADCD by C1q binding) after repeated NVX-CoV2373 or a single NVX-CoV2373 dose following repeated mRNA vaccine.Table:Summary of correlations between IgG1, IgG3, and IgG4 with neutralizing antibody titers (ancestral) and Fc effector functions in 2019nCoV-301 and 2019nCoV-307 studies. Results Increased nAb titers after NVX-CoV2373 were observed irrespective of the prior vaccine background, whereas increased IgG4 levels were only observed in recipients of mRNA vaccines. Spearman's rank correlation between nAb and Fc functions found significant positive correlations with anti-S IgG1 and IgG3 (Figure A, B), and significant negative correlation with anti-S IgG4 (Figure C) antibody responses (Table). Conclusion These are the first data to demonstrate the negative correlation of increased SARS-CoV-2 vaccine–induced anti-S IgG4 levels and nAb titers and Fc effector functions. The limitations of our data include small sample sizes, and potential differences attributable to vaccination and serum collection intervals. IgG4-mediated suboptimal nAb and reduced Fc effector function could reduce the vaccine effectiveness of the SARS-CoV-2 response, though more work is needed to understand its impact on the optimization of vaccine platform choice. Disclosures Raj Kalkeri, PhD, Novavax: Employee|Novavax: Stocks/Bonds (Public Company) Mingzhu Zhu, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Shane Cloney-Clark, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anand Parekh, M.Sc., Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Drew Gorinson, B.S., Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Rongman Cai, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Soham Mahato, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Louis F. Fries, III, MD, Novavax, Inc.: contractor for Novavax|Novavax, Inc.: Stocks/Bonds (Public Company) Lisa M. Dunkle, MD, Novavax, Inc: Employee|Novavax, Inc: Ownership Interest|Novavax, Inc: Stocks/Bonds (Public Company) Amy W. Chung, PhD, Novavax: Grant/Research Support Joyce S. Plested, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)

Mare colostrum quality and relationship with foal serum immunoglobulin G concentrations and average daily weight gains.

Foals suffer from total failure to transfer passive immunity (TFTPI) when serum immunoglobulin (IgG) is <4 g/L, and partial failure to transfer passive immunity (PFTPI) when serum IgG is 4-8 g/L. To explore risk factors for poor serum IgG concentration. Retrospective observational study. Data from 535 Thoroughbred foals born to 177 mares were analysed and included foal sex, birthweight, month and year of birth and colostrum Brix %. Associations between dam age and colostrum Brix (%); and between foal serum IgG and liveweight gains were also measured. Pre-suckle colostrum samples and foal blood samples were collected (by jugular venipuncture within 12-24 h of birth). IgG was estimated in mare colostrum and foal serum using Brix refractometry and turbidimetric immunoassay, respectively. Foals were weighed within 20 h of birth; daily until 7 days of age and weekly until 130 days of age. Mean foal serum IgG was 10.78 g/L (SD = 3.26) and mean mare colostrum Brix was 27.32% (SD = 5.96). A number of colostrum samples (20.9%, n = 112/535) measured <20% Brix and 20.4% of foals (n = 109/535) had serum IgG concentrations ≤8 g/L, 2.2% of foals (n = 12/535) had serum IgG less than or equal to 4 g/L and 18.1% (n = 97/535) had serum IgG between 4.1 g/L and 8 g/L. Foals had an average daily gain (ADG, kg) of 1.26 kg (SD = 0.14). Serum IgG (g/L) was associated with year of birth, birthweight (kg) and colostrum Brix (%). For every unit increase in foal birthweight (kg), there were small, significant increases in foal serum IgG (0.04 g/L, p = 0.04). Similarly, for every unit increased in mare colostrum Brix (%) there were small, significant increases in foal serum IgG (0.25 g/L, p < 0.001). Month of birth was significantly associated with colostrum Brix (%) and with average daily gains; with lower values for both outcome parameters with increasing calendar month. Increasing dam age at foaling was associated with lower colostrum Brix (%). Retrospective design with missing data, small convenience sample. Several risk factors were significantly associated with foal serum IgG and mare colostrum Brix (%) in the current work.

The Course of Dyskeratosis Congenita Masked by Crohn’s Disease in a Primary School-Age Child: Case Report

Background. Dyskeratosis congenita (DC) is an extremely rare genetically determined syndrome associated with the formation of bone marrow depression and clinically manifested by abnormal pigmentation of the skin, onychodystrophy, cobble-stone tongue, damage to the gastrointestinal tract, lungs, etc. Pathology may occur under the guise of other, more common diseases, which leads to late verification of the diagnosis and affects the prognosis. Case report. The boy D., aged 7 years, was hospitalized with complaints of dysphagia, a change in the shape of nails, ulcerative lesions of the tongue, insufficient weight gain, thin stool. Laboratory: decrease in hemoglobin, pancytopenia, low concentration of IgG in blood serum. According to esophagogastroduodenoscopy— esophageal stenosis. Crohn’s disease was suspected, but the condition worsened against the background of anti-TNF therapy. According to the results of full-exome sequencing, a pathogenic variant c.1058C&gt;T (chrX:154001427C&gt;T; NM_001363.3; p.A353V) was detected in the DKC1 gene in a hemizygous state, on the basis of which DC was confirmed. Conclusion. Practitioners should be wary of DC, since its manifestations can often mimic other, more common pathological conditions, in particular inflammatory bowel diseases. The correct interpretation of the combination of clinical, laboratory and instrumental changes can help to get closer to the correct diagnosis even before receiving the results of a molecular genetic study and determine therapeutic tactics.

The effect of Alpinia oxyphylla essential oil on growth performance, immune, antioxidant functions and gut microbiota in pigs

Alpinia oxyphylla, a perennial herb belonging to the Zingiberaceae family, has a long history of traditional medicinal use. The present study evaluated the efficacy of different concentrations of Alpinia oxyphylla essential oil (AEO) on the growth performance, serum antioxidation capacities, immune function, apparent digestibility of nutrients, and gut microbiota in fattening pigs. A total of 120 pigs were divided into five treatments, with six replicates each and four pigs per replicate. The pigs were fed a basal diet or basal diet with chlortetracycline (CTC) alone or AEO at 250, 500, and 1,000 mg/kg (referred to as groups AEO1, AEO2, and AEO3, respectively) for 35 days, preceded by a 7-day pre-feed period. The results show that there were no statistically significant differences in growth performance for any dose of AEO supplementation. AEO increased L-DLC content, total protein content and the activity of GSH in serum (p &amp;lt; 0.05). The AEO also exhibited a linear increase in serum IgG content (p &amp;lt; 0.05). Dietary supplementation with AEO improved apparent digestibility of crude ash and calcium (p &amp;lt; 0.05). In gut microbiota, AEO modified the diversity and abundance of bacterial communities in fattening pigs. The abundance of Dorea, Blautia, Butyricicoccus, Bulleidia, and Lactobacillus was higher in the AEO groups compared to the control group, while Clostridium and Turicibacter were lower. The Bifidobacteriales and Pseudomonas were abundant in group AEO1 and AEO3, respectively. In conclusion, dietary supplementation of 1,000 mg/kg AEO has the potential to improve growth performance, immunological, biochemical, and antioxidant statuses. Additionally, AEO can increase the efficiency of nutrient digestion and absorption through the regulation of gut microbiota.

Oreochromicin-2 shows antimicrobial and immunostimulant effect against respiratory pathogens in pigs.

Porcine respiratory diseases have a huge economic impact on pig production. The highest incidence of these diseases is commonly linked to Streptococcus suis, Pasteurella multocida and Bordetella bronchiseptica, some of which are zoonotic posing a risk to human health. The inappropriate and excessive use of conventional antibiotics, as usual procedure for treating respiratory diseases in pigs, has generated the emergence of antimicrobial resistance (AMR), which urgently requires the development of alternative approaches to current antimicrobials. Antimicrobial peptides (AMPs) have rapidly garnered interest as novel therapeutic candidates. Oreochromicin-2 (Oreoch-2), an AMP previously isolated from Oreochromis niloticus gills, has shown broad antibacterial properties against several species. However, studies about its effect on porcine respiratory pathogens and its potential use for the treatment of swine respiratory diseases are not available. In this work we determined the in vitro antimicrobial activity of the peptide against S. suis by a broth microdilution method. Oreoch-2 showed a MIC of 3.13μM against this pathogen. For in vivo experiments, Yorkshire x Landrace crossbred (LYxL35) weaning pigs aged 30-33days were allocated in pens containing ten pigs each. To study the influence of the peptide on health status, a total clinical score was determined. The administration of Oreoch-2 improved the clinical behavior of the animals, similar to the conventional antibiotic shotapen, respect to the placebo group. A reduction of bacterial loads in the respiratory tract and lungs was observed in Oreoch-2-treated animals as compared to the placebo group. It was shown that peptide treated-piglets displayed significantly higher serum IgG concentration compared to the control group. These results demonstrated Oreoch-2 potential as an antimicrobial and immunostimulant drug candidate against respiratory diseases in pigs.

Epstein-Barr nuclear antigen 1 antibody-based indices are increased in patients with multiple sclerosis

BackgroundMultiple sclerosis (MS) is a chronic central nervous system (CNS) disease, which is diagnosed by a combination of clinical symptoms and magnetic resonance imaging and measurement of an increased intrathecal antibody synthesis. Genetic as well as environmental factors influence onset of the disease, where especially Epstein-Barr virus (EBV) infection is directly involved in MS development. In this open retrospective study, we aimed to elaborate whether various serum and cerebrospinal fluid (CSF)-based EBV antibody indices may aid in the diagnosis of MS. MethodsEpstein-Barr nuclear antigen (EBNA)1 IgG concentrations in serum and CSF of relapsing-remitting (RR)MS patients (n=61) (M:F 28:33, average 40 years), optic neuritis patients (n=26) (M:F 9:17, average 47 years) and healthy controls (HCs) (n=15) (M:F 8:7, average 43 years) were determined by enzyme-linked immunosorbent assay. The obtained EBNA1 IgG levels were compared to factors such as total IgG, albumin concentrations, specific antibody index, and various serum- and CSF-based indices. ResultsSignificantly elevated EBNA1 IgG levels were detected in serum and CSF of RRMS patients compared to HCs. CSF EBNA1 IgG and indices based on specific CSF EBNA1 IgG associated with CSF albumin or serum EBNA1 IgG associated with total serum IgG obtained the highest sensitivities and complemented the IgG index and oligoclonal bands. ConclusionThese findings indicate that aforementioned indices may supplement existing indices and aid in the diagnosis of MS.

Disorders of acid-base balance promote rumen lipopolysaccharide biosynthesis in dairy cows by modulating the microbiome.

Disorders of acid-base balance in the rumen of dairy cows have a significant impact on their health and performance. However, the effect of transient differences in pH on susceptibility to subacute ruminal acidosis (SARA) and lipopolysaccharide (LPS) biosynthesis in dairy cows remains unclear. In this study, milk, serum, and rumen fluid samples from 40 Holstein dairy cows (on d 56 postpartum) with different rumen pH (2-4 h after morning feeding) were explored to investigate the difference of susceptibility to SARA and the correlation between microbiome, LPS and inflammation. These cows were categorized into low pH (LPH, pH ≤ 6.0, n = 20) and high pH (HPH, pH ≥ 6.5, n = 20) groups. The results showed that LPH group increased the concentrations of total volatile fatty acids, acetate, propionate, butyrate and valerate. However, milk yield and milk compositions were unaffected. Compared to the HPH group, the LPH group increased the concentrations of serum BHBA, NEFA, LPS, HIS, IL-2, IL-6, TNF-α, and MDA, and decreased the concentrations of serum IgA, IgM, IgG, SOD, T-AOC, and mTOR. In addition, the LPH group decreased the copies of Ruminococcus flavefaciens and increased the copies of Fibrobacter succinogenes. Microbial community analysis isupplendicated a significant difference in bacterial composition between the two groups. At the phylum level, Bacteroidota and Firmicutes were enriched in the LPH and HPH groups, respectively. At the genus level, the dominant bacteria in the LPH group were Prevotella. Additionally, the LPH group increased the proportions of Gram-negative phenotypes, potentially pathogenic phenotypes and LPS biosynthesis. The close correlation between two key enzymes for LPS synthesis LpxL and LpxM with rumen pH, inflammatory markers, and microorganisms indicates that low pH may increase the risk of inflammation by facilitating the lysis of Gram-negative bacteria and the release of penta-acylated LPS. Penta-acylated and hexa-acylated LPS may be mainly derived from Prevotella and Succinivibrionaceae_UCG-001, respectively. Overall, these results support the notion that transient low pH could reflect the risk of cows suffering from SARA and associated inflammation and is strongly associated with penta-acylated LPS. Our findings provide new insights into ruminant health improvement and disease prevention strategies.

Dietary supplementation with functional amino acids improves the capacity of growing pigs to cope with a health challenge

This study aimed to assess the effects of additional dietary supplementation with a blend of functional amino acids (FAA) with Thr, Trp, and Met as a preventive (prior to health challenge), curative strategy (during health challenge) or both targeting the performance, body composition, metabolic biomarkers of growing group-housed pigs raised under a health challenge. Additionally, the influence of these feeding strategies on pig response was investigated after the challenge (during the finishing phase). Sixty weaned piglets [6.3 ± 0.9 kg body weight (BW)] were distributed based on BW in a nursery barn to one of two dietary treatments (n = 30): control (CN) or supplemented with FAA blend (FAA+; 120 % of the Thr:Lys, Trp:Lys, and Met+Cys:Lys requirements) for 7 weeks. After 7 weeks, the pigs (27.9 ± 4.2 kg of BW) were distributed in a randomized complete block design to one of four treatments for the period of the health challenge period in the growing phase: pigs fed a CN diet during the nursery period were either maintained on a CN diet (control; n = 14) or switched to an FAA+ diet (curative strategy; n = 14), whereas the pigs fed an FAA+ diet during the nursery period were either fed a CN diet (preventive strategy; n = 14) or continued receiving an FAA+ diet (continuous strategy; n = 14). The health challenge consisted of subjecting growing pigs to batch mixing, poor housing conditions, and oral inoculation with Salmonella Typhimurium (ST). Poor housing conditions were maintained for 4 weeks (weeks 8–11). After this period, the pigs received the same standard diets for 9 weeks (weeks 12–20), and the facilities were cleaned daily. The health challenge increased the rectal temperature (P < 0.01) and serum concentrations of haptoglobin (P < 0.05), IgA (P < 0.05), IgG (P < 0.01), triglycerides (P < 0.01), creatinine (P < 0.01), and urea (P < 0.01), while reducing serum concentrations of lactate dehydrogenase (P < 0.01), albumin (P < 0.01), and glucose (P < 0.05). Pigs fed a continuous FAA+ diet trend towards lower fecal ST shedding (P < 0.10) than did the curative strategy pigs and had better fecal consistency scores (P < 0.01) than did the control pigs. During the challenge period, pigs fed FAA+ curatively or continuously demonstrated higher average daily gain and feed efficiency compared to control pigs (P < 0.01). Greater (P < 0.05) protein deposition (+30 %) and improved (P < 0.05) nitrogen retention efficiency (+20 % to curative and +30 % to continuous strategies) were observed in the pigs fed the FAA+ diet during the health challenge compared with the control pigs. Curative-fed FAA+ pigs had greater BW at the end of the finishing phase than did the control and preventive group (P < 0.05). In conclusion, the use of FAA supplementation as a curative or continuous strategy is highly effective at improving the performance and body composition of growing pigs under a health challenge.

Serum IgG Antibody against Helicobacter pylori and the CagA-VacA s1 Genotype as a Predictor of Gastric Cancer Development: A Case-control Study

Helicobacter pylori (H. pylori)-induced inflammation increases the risk of developing various upper gastrointestinal conditions which may progress to gastric cancer (CA). Early prediction and detection of infection are crucial for reducing cancer-induced mortality rates. The present case-control study aimed to investigate the combination of serum and molecular markers and H. pylori-associated gastro-duodenal conditions as risk factors for predicting CA development in dyspeptic patients. Consecutive gastric biopsies and blood samples were collected from 100 adult dyspeptic patients. Serum IgG antibody levels against H. pylori were determined, and receiver operating characteristic (ROC) analysis was performed. The expression of the virulence genes cagA and vacA was evaluated by polymerase chain reaction (PCR). A significant association was reported between the disease condition and the status of several risk factors, such as family history, serum IgG antibody concentration, and the virulence genes cagA and vacA. Among the 71 H. pylori-positive patients, 35.2% (25/71) had CA. Both cagA and vacA genes were found in 46 out of 71 (64.7%) patients, and 92% (23/25) of CA patients carried the cagA+vacA s1 gene. ROC analysis of the serum IgG concentrations revealed AUC values of 0.81 and 0.78 for differentiating patients with non-ulcer dyspepsia from those with ulceration/inflammation and CA, respectively. The concordance between the IgG-positive and PCR-positive patients was 84% (k value=0.41). Patients who had a family history of CA with an increased serum IgG concentration and the presence of H. pylori cagA-vacA s1 genotypes may be considered strong predictors of future development of gastric pathologies, including CA.

Korean Red Ginseng relieves the inflammation and oxidative stress induced by pseudo-typed SARS-CoV-2

BackgroundDeveloping antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global goal since the Coronavirus Disease 2019 (COVID-19) pandemic emerged in 2019. Korean Red Ginseng (KRG), recognized for its immunomodulating and antiviral properties, may be effective against SARS-CoV-2. Therefore, we aimed to investigate the efficiency of KRG in a human angiotensin-converting enzyme 2 (hACE2)-expressing mouse model infected with pseudo-typed SARS-CoV-2 (PSV). MethodsThe lung injury score was assessed using H&E staining, and the immune cell population shift in the lung and spleen was observed through flow cytometry. Serum IgM and IgG concentrations were quantified using enzyme-linked immunoassay (ELISA). Pro-inflammatory cytokine levels were measured by cytometric bead assay (CBA) and polymerase chain reaction (PCR). Additionally, the expression of NLR family pyrin domain containing 3 (NLRP3) and inflammation-related transcription factors was detected by immunoblotting. RNA-sequencing and antibody array assays reconfirmed gene expression in inflammation and oxidation. ResultsKRG extract was most effective in treating lung injuries and serum IgM and IgG levels. Also, immune cells, including neutrophils, were regulated in the lungs, and tumor necrosis factor-alpha (TNF-a) levels were reduced. NLRP3 and phosphorylated nuclear factor-κB (NF-kB) and activator protein 1 (AP-1) were downregulated. Heme oxygenase-1 (HO-1) expression was increased, indicating that KRG extract has antioxidant properties. RNA-sequencing and antibody array assays revealed that KRG extract regulates the expression of genes associated with inflammation and oxidative damage. ConclusionsThis study demonstrates that KRG extract may suppress PSV-induced inflammation and oxidative stress, making it a viable antiviral functional food.

A Comprehensive Review of IgG4 Related Disease Unraveling the Role of B and T Lymphocytes in the Pathogenesis of the Disease

IgG4-RD is a chronic fibro inflammatory disease characterized by a significant elevation of serum IgG4 concentration and marked infiltration of IgG4-positive plasma cells in the affected organs. A dense lymphoplasmacytic infiltrate and the formation of ectopic lymphoid structures are characteristic histopathological findings in an IgG4-RD lesions. These findings strongly suggest the preferential involvement of T and B lymphocytes in the development of this disease. We want to sum up the last evidences regarding the IgG4-RD with a focus on the role of the involvement of CD4+T-cell subsets and B lymphocytes.

IgG4-related disease: A common manifestation in an uncommon genus

Background: IgG4-related disease (IgG4-RD) is a recently described clinicopathological condition with a wide range of clinical manifestations: a dense lymphoplasmacytic infiltrate rich in IgG4positive plasma cells, fibrosis arranged in a storiform pattern, obliterative phlebitis, and, elevated serum IgG4 concentrations. Treatment involves corticosteroids and rituximab for the most severe cases. Case Presentation: Here we present two cases, two white females (ages 26 years and 50 years) IgG 4-RD with low back, flank pain, and retroperitoneal mass, with a compressive effect on the kidney and ureter and causing hydronephrosis. Biopsy of mass revealed infiltrates with IgG4 plasma cells, consistent with the diagnosis of IgG4 disease. The patients were treated with steroids, and rituximab showed significant improvement. Conclusion: Retroperitoneal fibrosis (RPF), a rarest cause of back pain in young adults, should be suspected in patients with back pain, renal dysfunction, and other associated symptoms. It is important to identify this particular cause as it is treatable and may be easily missed. The workup includes kidney function assessment and abdominal imaging using computet tomography (CT) or magnetic resonance imaging (MRI). Biopsy of the mass helps identify malignancy.

Comparative Analysis of the Potential Adaptability of Tibetan Dzo and Yellow Cattle Based on Blood Indices, Metabolites, and Fecal Microbiota.

This study aimed to investigate the differences in environmental adaptability between dzo and Tibetan yellow cattle by using corresponding assay kits to analyze blood indices, utilizing mass spectrometry for blood metabolite profiling, and performing 16S rDNA sequencing of fecal microbiota. Forty female cattle were randomly divided into a dzomo (female dzo) group (MG, n = 20) and a Tibetan-yellow-cattle group (HG, n = 20). After 150 days of uniform feeding, six cattle from each group were randomly picked for jugular blood sampling and collection of fecal microorganisms. The results showed that the serum albumin, creatinine, total protein, superoxide dismutase, IgG, and IgM concentrations in the MG group were higher (p < 0.05), whereas the serum triglyceride concentration was lower, compared to the HG group (p < 0.05). The higher level of phospholipids containing long-chain polyunsaturated fatty acids (PUFAs) (PC (18:5e/2:0), PC (20:5e/2:0), LPC 18:2, LPC 20:5) observed in the serum of the dzo suggests that they have an advantage in adapting to the challenging conditions of the plateau environment. The fecal microbiota analysis showed that Akkermansia was significantly enriched in the MG group; this might be the key bacterial genus leading to the strong adaptability of dzo. Our findings indicated the dzo's superior adaptation to the Tibetan Plateau's harsh environment.

Immunoglobulin G4 in primary Sjögren's syndrome and IgG4-related disease - connections and dissimilarities.

Primary Sjögren's syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases.

247 Interaction between colostrum and milk replacer supply on growth, development and fecal consistency of dairy surplus calves

Abstract This study examined the interactions between early life nutrition strategies and their impact on growth, development, and fecal consistency in surplus bull calves. Holstein-Friesian bull calves [n = 120; body weight (BW) = 43.1±3.56 kg] were enrolled. In the first 12 h after birth, calves were fed either 2 L (100 g of IgG) or 6L (300 g of IgG) of colostrum replacer (CR) to obtain either failure (F) or successful (S) transfer of passive immunity, respectively. Upon arrival at the facility, serum IgG concentrations were measured; therefore, F and S calves were identified accordingly and randomly assigned to one of two milk replacer (MR) feeding schemes: Moderate (Mod; ~8 L) or Low (Low; ~4 L). In total, there were 4 treatments resulting from the 2 × 2 factorial design: F-Mod, F-Low, S-Mod, S-Low (n = 30/treatment). Calves were individually housed and fed twice daily until d 42, gradually weaned until d 56, and had free access to straw and water during the study. On d 22, a calf pelleted starter was offered. To evaluate organ and gastroinstetinal tract development, 10 calves/treatment were euthanized at 84 d of age. Other measurements include weekly BW, daily intakes, and daily fecal score until d 21. Data were analyzed by PROC MIXED in SAS accounting for the fixed effects of block, CR, MR, and time, and their interaction. Time entered the model as a repeated statement, and initial BW was used as a covariable when appropriate. Initial BW was not different across treatments, whereas serum IgG was greater in S calves (S = 1,962.9 vs. F = 941.0 mg IgG/dL). During the study, BW was influenced by both CR (P = 0.001) and MR (P &amp;lt; 0.001), where S and Mod calves consistently exhibited greater BW when compared with F and Low calves, respectively. At d 84, Mod calves (F-Mod and S-Mod) were on average 18 kg heavier than Low calves. Similarly, Mod calves exhibited greater fresh tissue weights in the liver, pancreas, spleen, and both the small and large intestines (P &amp;lt; 0.05). Starter intake was influenced by MR (P &amp;lt; 0.001), with Low calves having the greatest intake before and during weaning. However, post-weaning starter intake was greater (P = 0.010) in Mod calves. Fecal consistency was influenced by CR (P = 0.001) and MR (P &amp;lt; 0.001), with S and Low calves having improved fecal consistency. Although no interactions were observed between CR and MR, these findings underscore the importance of considering both colostrum and MR levels in calf nutrition management to optimize growth and improve animal welfare during the early stages of life.

111 Factors affecting transfer of passive immunity in beef calves

Abstract Data from 9 calving experiments were used to investigate relationships of dam, calf, and colostrum factors with passive transfer in beef calves. Serum was collected at 48.33 ± 1.25 (SD) h of age for 313 calves, and single rear quarter colostrum yields were determined pre-suckling for dams of 117 calves. Serum and colostrum IgG concentrations were determined by ELISA. Relationship of serum IgG with colostrum variables was determined using Pearson correlation coefficients. Serum IgG was positively correlated (P ≤ 0.002) with colostrum IgG (r = 0.47) and protein (r = 0.45) concentrations and colostrum total IgG (r = 0.28) but tended to be negatively correlated (r = -0.17, P = 0.06) with colostrum yield. Based on passive transfer thresholds in the literature, 3 calves (0.96%) had &amp;lt; 8 mg/mL serum IgG, 16 calves (5.1%) &amp;lt; 16 mg/mL, and 43 calves (13.7%) had &amp;lt; 24 mg/mL. For this analysis, calves with serum IgG &amp;lt; 24 mg/mL at 48 h were considered to have failure of passive transfer (FPT). Continuous variables (dam BW and calf size, 48-h serum chemistry panel, and time to stand) were compared for FPT versus non-FPT calves using a mixed model with FPT class (fixed effect) and experiment (random effect). Calves with FPT had less (P ≤ 0.03) circulating triglycerides, glucose, calcium, magnesium, total protein, globulin, and gamma-glutamyl transferase but greater (P ≤ 0.001) circulating non-esterified fatty acids, sodium, chloride, and total bilirubin than non-FPT. Effects of categorical variables on calf 48-h serum IgG were determined using separate mixed models with variable (fixed) and experiment (random). Primiparous dams gave birth to calves that had less (P = 0.05) serum IgG at 48 h than multiparous dams. Calves born to moderate dams (BCS = 5) had less (P = 0.007) serum IgG than those born to fleshy dams (BCS ≥ 6) and tended to have less (P = 0.08) serum IgG than calves born to thin dams (BCS &amp;lt; 5). Calf sex, calving season, calving difficulty score, and vigor score at 10 min did not affect (P ≥ 0.19) serum IgG. Relationships of calf 48-h serum IgG with continuous variables was also determined using Pearson correlation coefficients, and only r ≥ 0.20 or ≤ -0.20 are reported. Serum IgG was positively correlated (P ≤ 0.005) with 48-h serum total protein (r = 0.75), globulin (r = 0.76), gamma-glutamyl transferase (r = 0.32), and potassium (r = 0.20). Serum IgG was negatively correlated (P &amp;lt; 0.001) with gestation length (r = -0.22) and 48-h serum albumin (r = -0.43), sodium (r = -0.24), and total bilirubin (r = -0.27). Overall, beef calves in this dataset generally had successful passive transfer that was associated with several dam, calf, and colostrum factors.

Genetic and environmental determinants of Immunoglobulin G in kid serum and adult colostrum of dairy goats

Immune competence is a key factor in the health and resilience of dairy ruminants. The aim of this study was to study immunoglobulin G concentration in serum shortly after birth and in colostrum of lactating animals as proxy of passive immune transfer and colostrum quality, respectively, and thus provide new health and resilience indicators for selection. Data from 424 female kids and 203 primiparous goats, reared on an INRAE experimental farm, were analyzed. IgG concentration was measured in kid serum and goat colostrum, respectively, using the radial immunodiffusion technique. Linear models were used to identify factors of variation in serum and colostrum IgG concentration, and health events were monitored for 5 weeks after birth to measure the impact of passive immune transfer on kids' health. We found a significant effect of serum IgG level on hindquarters cleanliness score (as a proxy of digestive troubles) and nasal and ocular discharge. As expected, the absorption of IgG in the days following birth is essential to ensure the passive transfer of immunity from the mother to the youngster, and provide immune protection. Genetic parameters were estimated for serum IgG concentration in kids and for colostrum characteristics in primiparous goats. Heritability of serum IgG in kids was not significantly different from zero. This low value, with large SE, may be due to the limited sample size and large environmental variability likely not accounted for. Especially, we could not adjust for the amount of IgG that was ingested by the kid, which can have a significant effect on serum IgG and possibly on heritability estimates. Heritability of colostrum traits were moderate, with estimates of 0.25 (±0.16), 0.35 (±0.16), and 0.25 (±0.16) for IgG concentration, IgG mass and colostrum volume, respectively. Genetic correlations with milk production showed high standard errors due to small numbers. However, estimates suggest a negative genetic association between production and IgG concentration in colostrum (rg = -0.44 ± 0.33), probably linked to a positive association with total colostrum volume. The significant heritabilities that were estimated for the first time demonstrate the existence of genetic control of colostrum quality in goats, and open up opportunities for selection in this species.

Feeding a Saccharomyces cerevisiae Fermentation Product to Mares in Late Gestation Alters the Biological Activity of Colostrum.

The quality of equine colostrum is typically defined by refractometry or the concentration of maternal antibodies. However, the activity of other equine colostral bioactive molecules has not yet been investigated. This study analyzed whether the administration of a Saccharomyces cerevisiae fermentation product (SCFP) influences the biological activity of mare colostrum and whether the biological activity of colostrum has a lasting immunomodulating effect for foals. A total of fourteen pregnant mares received 20 g/day of a SCFP for a period of twelve weeks prior to the calculated date of birth (SCFP-group). Twelve pregnant mares without supplementation served as controls (CON). Colostral Brix values were determined within three hours after parturition. The concentration of IgG in blood sera and colostrum samples was determined with an ELISA. The biological activity was determined in a cell growth assay with a porcine epithelial cell line (IPEC-J2). Mares (at three weeks before the calculated date of birth) and foals (at the age of 5-8 months) received a parenteral active vaccination against influenza and tetanus. The administration of SCFP did not alter the mare's serum and colostrum IgG concentrations and did not exert a significant influence on the mares' early response to the vaccination. Growth and diarrhea episodes were comparable between foals of supplemented mares (SCFP) and foals of mares without supplementation (CON). Colostrum samples from SCFP-supplemented mares exhibited heightened biological activity. While SFCP and CON foals did not differ in their early response to vaccination, the vaccination-induced alterations in circulating neutrophilic granulocyte numbers were significantly correlated with the biological colostrum activity. These findings suggest that the supplementation of mares in late gestation with SCFP can enhance the biological activity of colostrum, which subsequently influences the innate immune responses of their offspring in later life.

Idiopathic hyalinizing fibrosclerosis: A systemic steroid-resistant condition distinct from IgG4-related disease

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of ‘idiopathic hyalinizing fibrosclerosis’ for this under-recognized, rare, systemic condition.

Relationship Between Growth Performance, Passive Immunity and Health In Preweaned Lambs

This study was designed to investigate associations between transfer of passive immunity, selected illness-es (diarrhoea, pneumonia, and fatigue anorexia syndrome-FAS) and growth performance [body weight (BW) and aver-age daily gain (ADG)] in preweaned lambs. A total of 347 lambs were blood sampled at 24±1 h of age after birth and the serum IgG concentration for each lamb was measured after colostrum intake using a commercial ELISA kit. Lambs were weighed on a scale immediately after birth (before colostrum intake) and reweighed on day 28 (end of neonatal period) and day 84 (age of weaning). Lambs ADG was calculated from 0 to 28 d of life, from 29 to 84d of life, and from 0 to 84 d of life. Growth performance (BW and ADG) of lambs with diarrhoea and FAS in the neonatal period and with pneumonia in the postneonatal period was significantly lower than that of healthy lambs of the same period (P&amp;lt;0.05). BW of lambs with serum IgG concentration at 24th hour after the birth (SIgGC-24)&amp;lt;600 mg/dL and &amp;lt;1000 mg/ml was significantly lower on days 28 and 84 than that of lambs with SIgGC-24 &amp;gt;600 mg/dL and &amp;gt;1000 mg/ml (P&amp;lt;0.001). Simi-larly, the ADG of lambs with SIgGC-24 &amp;lt;600 mg/dL and &amp;lt;1000 mg/ml was significantly lower on days from 0-28, 29-84 and 0-84 of age than those of lambs with SIgGC-24 &amp;gt;600 mg/dL and &amp;gt;1000 mg/ml (P&amp;lt;0.001). In conclusion, our find-ings show that low serum IgG concentration in lambs, as well as the presence of pneumonia, diarrhea and FAS, reduc-es growth performance in pre-weaning lambs.