Search Results (1,835)

Background: Fermented polysaccharides derived from Morinda citrifolia (noni) have been suggested to modulate innate immune responses, but clinical evidence remains limited. Objectives: This randomized, double-blind, placebo-controlled trial evaluated the effects of fermented noni polysaccharides on natural killer (NK) cell activity and immune-related biomarkers in adults with recurrent upper respiratory tract infections (URTIs). Methods: A total of 100 adults aged 40 to <75 years with a documented history of ≥2 episodes of upper respiratory tract infection in the prior 12 months were randomly assigned to receive fermented noni polysaccharides (487.5 mg/tablet, two tablets once daily; 975 mg/day of FNP extract) or a matched placebo for 8 weeks. The primary endpoint was the change in NK cell activity at effector-to-target (E:T) ratios of 50:1, 25:1, and 12.5:1, assessed using K562 NK-sensitive target cells. Secondary endpoints included circulating cytokines (IFN-γ, TNF-α, IL-2, IL-6, IL-10, IL-12, IL-1β) and immunoglobulin G (IgG). Eighty-four participants (43 treatment, 41 placebo) were included in the modified intention-to-treat/full analysis set (mITT/FAS); 81 participants (41/40) constituted the per-protocol set (PPS). Primary efficacy was analyzed in the mITT/FAS. This trial was retrospectively registered at CRiS (KCT0011316) after trial completion; the IRB-approved protocol was finalised before enrolment and remained unchanged thereafter. Results: NK cell activity in the treatment group increased from baseline at all three E:T ratios, whereas it slightly decreased in the placebo group. Adjusted between-group LS mean differences (95% CI) were +8.94 (−0.61, 18.50; p = 0.066) at E:T 50:1, +7.68 (−1.14, 16.50; p = 0.087) at 25:1, and +3.29 (−2.95, 9.54; p = 0.145) at 12.5:1, all favouring treatment but not reaching the conventional threshold for significance in the mITT/FAS. Prespecified PPS sensitivity analyses reached significance at E:T 50:1 (+11.03; p = 0.025) and 25:1 (+9.94; p = 0.028). Selected cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-1β) increased to a greater extent in the treatment group than in the placebo group, whereas TNF-α, IL-12, and IgG were unchanged. URTI incidence at week 4, week 8, and cumulatively did not differ significantly between groups. The intervention was well tolerated, with no serious adverse events and no treatment-related discontinuations. Conclusions: Compared with placebo, fermented noni polysaccharide supplementation showed numerically greater increases in NK cell activity at all three E:T ratios (50:1, 25:1, and 12.5:1) in the primary mITT/FAS analysis, although these between-group differences did not reach statistical significance. Prespecified per-protocol set (PPS) sensitivity analyses showed significant between-group differences at E:T ratios of 50:1 and 25:1. The treatment group also showed greater increases in selected cytokines (IFN-γ, IL-2, IL-6, IL-10) relative to placebo. No significant between-group differences were observed in URTI incidence, IgG, GARS, WBC, or leukocyte subset proportions. These exploratory biomarker findings, in the absence of safety signals, suggest a possible immunomodulatory profile but do not establish clinical efficacy. Confirmation in larger, prospectively registered trials with clinically adjudicated infection-related endpoints is warranted. Full article

The effects of substituting soybean meal with black soldier fly larvae (BSFL) meal on the growth performance, immunological response, intestinal morphology, and gut microbiota of Pekin ducks were assessed. A total of 150 one-day-old Pekin ducks were randomly allocated to three isonitrogenous and isocaloric diets: a control diet (0% BSFL), and diets including 10% or 30% BSFL meal (T10 and T30, respectively). Over 42 days, growth metrics, organ indices, serum and jejunal immune parameters, intestinal morphology, and caecal microbiota composition were evaluated. Ducks fed BSFL-containing diets exhibited a significant increase in spleen index compared to the control group (0.06% ± 0.02% for T10 and T30 vs. 0.05% ± 0.01% for control, p < 0.05), while other organ indices and growth performance remained unaffected. Serum levels of immunoglobulins (IgG, IgM, sIgA), cytokines (IFN-γ, IL-2), and complements (C3, C4) were significantly elevated in both BSFL groups (p < 0.05). Jejunal immune indices, including IgG, IgM, IL-2, and C3, were also significantly higher in the T10 group (p < 0.05). Intestinal morphology showed a significantly increased villus-to-crypt ratio in the duodenum and jejunum (p < 0.05). Analysis of gut microbiota indicated that BSFL supplementation was associated with changes in caecal microbial composition, including a lower relative abundance of Proteobacteria. However, alpha diversity indices did not differ significantly among groups. These findings suggest that BSFL meal can replace soybean meal at inclusion levels up to 30% in Pekin duck diets without adversely affecting growth performance, while enhancing select immune parameters and modulating gut microbiota composition. Full article

Grapevine branch and leaf silage (GBLS), a polyphenol-rich unconventional forage, exhibits antimicrobial and antioxidant properties that can benefit animal health and productivity. A total of 60 healthy six-month-old Kazakh rams (43.29 ± 4.55 kg, p > 0.05 for initial body weight among groups) were randomly assigned to three dietary groups, each consisting of four replicates with five rams per replicate. The control group (CK) was fed a basal diet based on whole-plant corn silage, whereas the experimental groups received diets in which 50% (GBLS50%) or 100% (GBLS100%) of the corn silage was replaced with GBLS. A 10-day adaptation period preceded the 90-day formal feeding trial. Results showed a significant quadratic response for average daily gain (ADG) and average daily feed intake (ADFI) across GBLS substitution rates (p < 0.05), with the 50% level yielding the highest values. Specifically, ADFI at the 50% replacement level was significantly higher than that of the control (p < 0.05), confirming an inverted U-shaped response with 50% as the optimal substitution rate. However, in-depth analysis of serum biochemical parameters revealed that GBLS supplementation significantly reduced serum concentrations of total cholesterol, triglycerides, urea nitrogen, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA), while significantly increasing levels of immunoglobulins (IgA, IgM, IgG), superoxide dismutase (SOD), and catalase (CAT) (p < 0.05). Rumen fermentation analysis showed that the GBLS50% group had significantly lower concentrations of acetate, butyrate, and total volatile fatty acids (VFA) (p < 0.05). In the rumen microbiota study, no significant differences were observed in alpha or beta diversity or at the phylum level between groups (p > 0.05); however, the abundance of Lactobacillus gasseri was significantly reduced in the GBLS50% group (p < 0.05). Metabolomic profiling identified 43 significantly altered metabolites—27 upregulated (e.g., PE (18:1(9Z)/0:0) and 12,14-pentacosadiynoic acid) and 16 downregulated (e.g., deoxyadenosine). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis highlighted purine metabolism as a significantly altered pathway (p < 0.05), providing insight into the potential metabolic mechanisms underlying the physiological effects of GBLS in rams. In conclusion, replacing 50% of whole-plant corn silage with grapevine branch and leaf silage improves growth performance trends and significantly enhances immunity and antioxidant capacity in Kazakh rams. Full article

Background/Objectives: AA amyloidosis is a serious complication of chronic inflammation, which may arise in the setting of inborn errors of immunity (IEIs) due to recurrent or persistent infections. Common variable immunodeficiency (CVID) is the most frequent symptomatic IEI in adults, yet its association with secondary AA amyloidosis remains rarely reported. Case presentation: We describe a 37-year-old male with a history of recurrent pneumonia, chronic sinusitis, and osteomyelitis with sepsis since childhood. At age 33, he developed bilateral pneumonia after COVID-19, followed by repeated lower respiratory tract infections. At age 36, nephrotic syndrome (proteinuria 10.69 g/day, hypoalbuminemia) led to kidney and gastric mucosa biopsies, which confirmed AA amyloidosis. Immunological workup revealed panhypogammaglobulinemia (IgG 0.1 g/L, IgA 0.01 g/L, IgM 0.28 g/L), markedly reduced switched memory B cells, and an inverted CD4⁺/CD8⁺ ratio. Chest CT showed bronchiectasis, bronchiolitis, and mediastinal lymphadenopathy. Whole-exome sequencing excluded known monogenic IEIs, autoinflammatory, or hereditary amyloidosis genes; a heterozygous likely pathogenic variant in ODAD2 (associated with primary ciliary dyskinesia) was considered incidental. A diagnosis of CVID with secondary AA amyloidosis was established. Conclusions: This case illustrates that CVID may remain undiagnosed for decades and present with secondary AA amyloidosis as the first major complication. In any patient with nephrotic syndrome and a history of recurrent or unusual infections, an IEI should be actively excluded. Early recognition of CVID and appropriate immunoglobulin replacement therapy can prevent infectious exacerbations and potentially halt amyloid progression. Full article

Ring chromosome 14 (RC14) syndrome is an ultra-rare disorder characterized by drug-resistant epilepsy, intellectual disabilities, autism, and recurrent infections, suggesting a possible underlying immune dysregulation. We analyzed immunoglobulin G (IgG) N-glycosylation profiles in six RC14 patients and compared them with age-matched healthy controls using ultra-high-performance liquid chromatography (UHPLC) coupled with fluorescence detection (FLR) and high-resolution electrospray ionization mass spectrometry (ESI-MS). Patients showed decreased galactosylation and sialylation, resembling pro-inflammatory patterns observed in autoimmune diseases. These alterations were not observed in total serum glycoproteins, indicating a selective effect on IgG. One patient treated with intravenous immunoglobulin (IVIG) showed clinical improvement, which led us to investigate causality. Full article

Barley hay (BH), characterized by high crude protein, neutral detergent fiber, and various bioactive compounds, is hypothesized to optimize ruminal microbiota and enhance systemic immune responses in sheep. This study assessed how the graded substitution of traditional forage with BH impacts ruminal fermentation, microbiota composition, and blood immune and antioxidant status in sheep. Forty-five male Dorper × Small-tailed Han crossbred lambs (aged 110 ± 10 days, BW 33.93 ± 1.11 kg) were stratified into five cohorts (n = 9 each), including a control (CON) and four experimental groups (BH25, BH50, BH75, and BH100), where BH replaced 25%, 50%, 75%, and 100% of their forage mixture, respectively. Results showed that BH supplementation consistently increased ruminal acetate concentrations. Specifically, BH75 and BH100 significantly enhanced the acetate-to-propionate ratio (p < 0.05) and concurrently reduced NH₃-N concentrations in BH50 and BH100 (p < 0.05). Regarding ruminal microbiota, BH treatment did not alter alpha diversity but significantly enriched fiber-degrading bacteria, including Clostridia, Bacteroidales, and Prevotella, whereas the CON group favored Eubacterium. Blood analysis indicated a time-dependent modulation of immune and antioxidant markers. At day 30, BH treatment resulted in elevated immunoglobulin A (IgA), immunoglobulin G (IgG), interleukin-6 (IL-6), and malondialdehyde (MDA) levels (p < 0.05), whereas catalase (CAT) concentrations were markedly reduced (p < 0.05). By day 60, BH continued to enhance IgA, IgG, and IL-6 levels; meanwhile, tumor necrosis factor α (TNF-α) levels were up-regulated by BH25-BH75 (p < 0.05), while supplementation with BH75 and BH100 led to a decline in interleukin-4 (IL-4), CAT, and interleukin-10 (IL-10) (p < 0.05). Correlation analysis showed that a positive correlation was observed between total volatile fatty acids and Prevotella UCG-003/001, which conversely displayed a negative relationship with IgM. The norank f Eubacterium coprostanoligenes group showed an inverse association with valerate and IgG, but a positive correlation with interleukin-1β (IL-1β). In parallel, the norank f Bacteroidales RF16 group exhibited an inverse association with NH₃-N and CAT, while unclassified c Clostridia was positively correlated with IL-1β. In conclusion, BH substitution modulates ruminal fermentation and immune responses by enriching fiber-degrading bacteria, though it may trigger oxidative stress. Given that BH100 maximized acetate and immunoglobulin production while minimizing MDA levels, complete replacement appears superior to partial substitution. Full article

Salvia sclarea L. extract contains various bioactive components such as flavonoids and fatty acids, exhibiting anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the effects of Salvia sclarea L. extract on the gut microbiota and serum metabolome in lambs. Sixty 2-month-old Chinese Merino female lambs (body weight 20 ± 2 kg) were randomly assigned to five groups. The control (CK) group received the basal diet only, while the treatment groups received the basal diet supplemented with 0.04 mL/kg (CL1), 0.08 mL/kg (CL2), 0.12 mL/kg (CL3), and 0.16 mL/kg (CL4) of Salvia sclarea L. extract, respectively. The results showed that Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria were identified as the dominant phyla across all groups (>90%). Compared with the CK group, CL1 and CL2 groups significantly reduced the relative abundance of Tenericutes (decreased by 38.2% and 32.9%, respectively, p < 0.05); the relative abundance of Patescibacteria in the CL1 group was significantly lower (decreased by 55.2%, p < 0.05). At the genus level, Ruminococcaceae constituted a substantial proportion, including Ruminococcaceae UCG-005, UCG-010, UCG-014, and NK4A214 group. STAMP analysis revealed that Klebsiella was significantly enriched in CL2, CL3, and CL4 groups compared to the CK group (p < 0.05). Correlation analysis between microbiota and immune indices showed that Christensenellaceae R-7 group was significantly negatively correlated with TNF-α (p < 0.05); Ruminococcaceae UCG-005 was significantly negatively correlated with IFN-γ (p < 0.05) and showed a negative correlation trend with immunoglobulins (IgA, IgG, IgM). Conversely, Ruminococcaceae UCG-014 was significantly positively correlated with IL-4 (p < 0.05) but showed a negative correlation trend with IgM. Untargeted metabolomics analysis identified 8, 18, 25, and 20 differential metabolites in CL1, CL2, CL3, and CL4 groups, respectively. Notably, 3-hydroxy-7-methoxyflavone and Gamma-Glu-Cys were significantly upregulated across all treatment groups. KEGG pathway enrichment analysis indicated that these differential metabolites were primarily involved in nucleotide metabolism, fatty acid biosynthesis, and oxidative stress-related pathways. Further Spearman correlation analysis revealed significant associations between gut microbiota and differential metabolites. Specifically, g_Klebsiella was significantly positively correlated with 3-Hydroxycapric acid and 3-hydroxy-7-methoxyflavone (p < 0.05). In conclusion, Salvia sclarea L. extract modulates host energy metabolism by regulating nucleotide metabolism and fatty acid biosynthesis, and enhances immune function by alleviating oxidative stress, through the remodeling of gut microbiota and serum metabolome. Full article

Background and aims: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease among children. Our study aimed to evaluate the prevalence of hypogammaglobulinemia among pediatric patients with AD and to characterize the clinical and laboratory findings of patients diagnosed with AD and hypogammaglobulinemia. Method: The electronic files of 1850 patients aged 0–18 years diagnosed with AD between 2020 and 2022 in the Pediatric Immunology and Allergy Clinic of Bursa Medical Faculty City Hospital were retrospectively analyzed. During this period, all patients newly diagnosed with atopic dermatitis at our clinic were systematically screened for their serum immunoglobulin (Ig) levels (IgG, IgA, and IgM) at the time of initial presentation. We included 200 AD patients with hypogammaglobulinemia. Disease severity was classified using the Scoring Atopic Dermatitis (SCORAD) index. Multivariate logistic and linear regression analyses were performed to identify independent determinants of disease severity, considering age, sex, eosinophil counts, total IgE, food allergies, and baseline immunoglobulin levels. Results: The prevalence of hypogammaglobulinemia among the 1850 screened children with AD was 10.8% (200/1850). Of the 200 patients included in this study, 128 (64%) were male, and 72 (36%) were female. The median age at first clinic presentation was 8 months (interquartile range (IQR) 25–75%: 5–16). According to the Scoring Atopic Dermatitis (SCORAD) index, AD severity was mild in 150 (75%) patients and moderate-to-severe in 50 (25%). Food allergy sensitization was present in 72 (36%) patients. Patients with moderate-to-severe AD had significantly lower IgG (300 vs. 374 mg/dL; p < 0.001; r = −0.346), IgA (10 vs. 14 mg/dL; p = 0.004), and IgM (38 vs. 51 mg/dL; p = 0.001) levels when compared with those with mild disease. Multivariate logistic regression confirmed that lower IgG was the only immunoglobulin independently associated with moderate-to-severe AD (OR = 1.97 per 100 mg/dL decrease; 95% CI: 1.15–3.39; p = 0.013), while food allergy was the strongest independent predictor of the SCORAD index (β = +11.97; p < 0.001). None of the patients received intravenous immunoglobulin (IVIG) treatment. Of the 142 patients who underwent serial serum immunoglobulin measurements, 56 (39%) achieved age-appropriate normal IgG levels, while hypogammaglobulinemia persisted in 86 (61%). Conclusions: We found a higher frequency of hypogammaglobulinemia in patients with AD in our study, as compared with previously reported rates of THI in children from the general pediatric population. Although our study showed an increase in IgG levels during the follow-up period in many patients, it emphasizes the need for long-term immunological monitoring, especially in patients with moderate-to-severe AD. Full article

Tributyrin, a short-chain fatty acid derivative, has been shown to hold potential in improving intestinal health in livestock and poultry. However, its multidimensional effects on the health of meat pigeons, particularly during the young pigeon stage, remain unclear. This study aimed to investigate the comprehensive effects of dietary tributyrin supplementation on the growth, health status, intestinal function, and metabolic profile of young pigeons. A total of 100 healthy 29-day-old White King pigeons, with half male and half female, were randomly divided into a control group (fed a basal diet) and a treatment group (fed a basal diet supplemented with 1500 mg/kg tributyrin) for a 35-day trial. The results showed that compared with the control group, young pigeons in the treatment group had significantly reduced serum triglyceride levels, alanine aminotransferase activity, and concentrations of pro-inflammatory cytokines (TNF-α, IL-6), along with significantly increased levels of high-density lipoprotein, immunoglobulin G, total antioxidant capacity, and glutathione peroxidase activity. Concurrently, the villus height-to-crypt depth ratio in the jejunum and ileum was significantly elevated, indicating improved intestinal morphological structure. Untargeted metabolomics analysis further revealed significant changes in the relative abundances of 13 key differential metabolites (e.g., L-carnitine, pyridoxamine, indoleacetic acid) in the small intestinal contents of the treatment group. These metabolites were mainly enriched in metabolic pathways such as 2-oxoCarboxylic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. In conclusion, dietary supplementation with 1500 mg/kg tributyrin can exert multifaceted beneficial effects on young pigeon health by improving lipid metabolism, enhancing immune and antioxidant functions, optimizing intestinal structure, and regulating the local metabolic network. This study provides a theoretical basis for the application of tributyrin as a functional additive in the green and healthy production of meat pigeons. Full article

Largemouth bass (Micropterus salmoides) represents an important freshwater aquaculture species. Dietary protein strategies significantly influence growth performance, immune markers, and intestinal microbiota homeostasis. This study evaluated the physiological effects of five phased protein regimens on juvenile largemouth bass (9.77 ± 0.03 g) over 60 days. A constant 46% protein diet (CON) served as the control, compared with four dynamic regimens (LLH, LMH, LHH, HML) comprising low (L, 43%), medium (M, 46%), or high (H, 50%) protein levels across three 20-day phases. Seven hundred fish were randomly allocated into five groups (four replicates each). Daily feed intake was recorded, body weight was measured at the start and end, and survival rates were monitored. Post-trial assessments included body composition, serum biomarkers, intestinal morphology, and intestinal microbiota. Results showed that the LHH regimen significantly increased immunoglobulin M, complement C3 and C4, lysozyme activity, catalase, glutathione peroxidase, and total antioxidant capacity compared to the CON group. The LHH group also exhibited a reduced relative abundance of Stenotrophomonas_A. Functional predictions indicated downregulation of limonene/pinene degradation and the renin–angiotensin system. The LHH feeding regimen synergistically enhances immune-antioxidant function and optimizes intestinal microbiota in juvenile largemouth bass. Full article

To investigate the effects of Wuwei Jianpi San (WJPS), a Chinese herbal compound feed additive, on rumen microecology, host metabolism, and immune function in healthy yaks (Bos grunniens), and to determine the optimal supplementation level, 32 yaks with similar initial body weight were randomly assigned to four groups: a control group and three groups receiving 0.5%, 1.0%, or 2.0% WJPS for 90 days. Growth performance, hematological indices, serum antioxidant and immune parameters, tryptophan metabolites, ruminal short-chain fatty acids (SCFAs), and rumen microbiota were analyzed. WJPS supplementation improved growth performance, as shown by a reduced feed-to-gain ratio in all treated groups and tended to increase average daily gain in the 2.0% group. It also enhanced hematological, antioxidant, and immune status, evidenced by increased white blood cell (WBC) and lymphocyte (Lym) counts and elevated interleukin-2 (IL-2), immunoglobulin G (IgG), and superoxide dismutase (SOD) levels. Moreover, 2.0% WJPS increased total SCFAs, acetate, and n-butyrate, while WJPS reduced kynurenine pathway metabolites, including kynurenine, 3-hydroxykynurenine, and quinolinic acid. Metagenomic analysis showed that WJPS tended to shape rumen microbial composition by increasing Bacillota and decreasing Bacteroidota, and these microbial changes were associated with host immune indices and tryptophan metabolism. Overall, 2.0% WJPS showed the best comprehensive effect. Full article

Ophiopogon japonicus (O. japonicus) by-products contain abundant nutrients and bioactive substances. In this study, we evaluated their effects on production performance and intestinal health in meat rabbits. Firstly, we measured the nutrient levels of O. japonicus by-products along with its digestibility in meat rabbits. Then, we replaced dietary alfalfa meal with O. japonicus by-products to evaluate its effects on growth performance, carcass traits, apparent digestibility, and intestinal immunity in meat rabbits. The results showed that the effects of O. japonicus by-products on growing meat rabbits varied over time. In the early phase (days 1–21), it significantly depressed average daily gain (ADG, p < 0.001) and average daily feed intake (ADFI, p < 0.001), and increased feed to gain ratio (F:G) (p < 0.001). However, in the later phase (days 22–35), a compensatory response emerged, with significantly increased ADG (p < 0.001) and reduced ADFI (p < 0.01) and F:G (p < 0.001). Despite this compensatory growth, the growth performance and feed efficiency for the entire experimental period were not improved. O. japonicus by-products decreased carcass weight significantly (p < 0.001), but did not significantly affect dressing percentage and meat traits (p > 0.05), while it significantly reduced the digestibility of crude protein (CP, p < 0.05), increased that of crude fiber (CF, p < 0.001), and reduced the activities of amylase (p < 0.01) and increased trypsin in cecal contents (p < 0.05). Additionally, O. japonicus by-products elevated the levels of secretory immunoglobulin A (sIgA) and interleukin-10 (IL-10) in ileal mucosa (p < 0.05). They did not significantly affect the cecal microbial community or short chain fatty acid (SCFA) levels (p > 0.05). Our research indicated that O. japonicus by-products possess a balanced nutritional composition and improve intestinal immunity in rabbit production, making them a viable feed ingredient to partially replace alfalfa meal. Full article

Background/Objectives: Excessive dietary inorganic phosphate (Pi) as a food additive poses potential health risks. Methods: This study investigated the impact of excessive dietary inorganic phosphate on intestinal and immune homeostasis in mice using gradient Pi exposure combined with an inflammatory model. Results: Pi overload induced atrophy in the thymus, spleen, and kidney; damaged the intestinal barrier; reduced the villus height-to-crypt-depth ratio; and decreased goblet cell numbers. Altered levels of serum sIgA and IgE, as well as intestinal IgA, IgG, IgE, and IgM, together with decreased IFN-α, indicated altered levels of immunoglobulins and cytokines under Pi treatment. Proteomic analysis revealed differential expression of key proteins, including CNTFR and Bcl2l1 in the JAK/STAT pathway and metabolic regulators CPT1α and IDH1, when comparing Pi-treated mice with the control group. Conclusions: These preliminary findings suggest that Pi may affect intestinal mucosal barrier function and systemic immune response through immune regulation and mitochondrial metabolic pathways, providing preliminary insight into the potential health implications of Pi overconsumption in humans. Full article

At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening may be useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are major GC risk factors. We recently developed a noninvasive test called the DSC test-based on the patient’s age, sex, their serum PGI and PGII, anti-HP immunoglobulin (IgG), and gastrin G17 levels-predicting GC risk as low (score 0, S0) or high (score 2, S2). The comparative investigation at the serum protein level of the two different patient groups detected by our DCS test (S0 and S2) may undoubtedly help to identify gastric disease-dependent proteins, resulting from bacterial infection or gastric mucosa inflammation, as well as get better insight into the molecular scenario associated with pre-cancerous conditions. We used an untargeted liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based proteomic profiling approach, followed by univariate statistical analysis to compare the different DSC groups across two patient cohorts (exploratory and validation). Significantly differentially abundant proteins differing more than 1.5-fold between S0 and S2 groups were selected and validated, and their putative role(s) in gastritis and GC were discussed. In both the exploratory and the validation cohorts, four proteins (beta-2-microglobulin, EGF-containing fibulin-like extracellular matrix protein 1, complement factor D, and cystatin-C) were more abundant, while two (sex hormone-binding globulin and pregnancy zone protein) were less abundant in the sera of S2 individuals (|fold change| ≥ 0.6, p < 0.05, t-test). The higher presence of beta-2-microglobulin (B2M) and the lower content of pregnancy zone protein (PZP) in S2 sera were validated by immunoblotting. Replacing age and sex in our DSC model with two specific candidate biomarkers can lead to a refined, albeit modest, improvement in classification accuracy. This study identified a proteomic signature that was differentially associated with the sera of patients with a different risk to develop advanced atrophy/GC according to the DSC test. Moving from a demographic model to a proteomic-driven model can better reflect the personalized biology of pathological processes associated with DSC. Full article

Background: Pregnancy presents unique immunological and obstetrical challenges for women with Common Variable Immune Deficiency (CVID). No standardized guidelines currently exist to guide pregnancy management, as CVID is a rare diagnosis, with pregnancy outcomes limited to case reports and case series. Establishing a structured approach to care is important to optimize maternal and fetal outcomes. Methods: A narrative review of the literature with a structured search was performed to detail pregnancy outcomes in CVID and management strategies. A 10-year retrospective chart review of women with CVID who became pregnant while receiving care at the McGill University Health Centre between January 2015 and January 2025 was conducted to add to the existing clinical data. Results: Pregnancy outcomes were improved through pre-conception planning, regular serum Immunoglobulin G (IgG) monitoring, trimester-based immunoglobulin replacement dose adjustments, proactive management of autoimmune or infectious complications, and multidisciplinary care. Subcutaneous immunoglobulin may offer better flexibility and stability of IgG levels. Conclusions: In the available observational literature and our institutional experience, many patients with CVID have carried pregnancies to term with favorable maternal and neonatal outcomes when managed with IgRT and multidisciplinary coordination. We outline a stepwise multidisciplinary framework for clinicians caring for women with CVID who are planning or undergoing pregnancy, and we identify gaps in knowledge for future studies. Full article