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Humanized mice are limited in terms of modeling human immunity, particularly with regards to antibody responses. Here we constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated KitW-41J mutant immunodeficient pups with human cord blood CD34+ cells, followed by 17β-estradiol conditioning to promote immune cell differentiation. THX mice reconstitute a human lymphoid and myeloid immune system, including marginal zone B cells, germinal center B cells, follicular helper T cells and neutrophils, and develop well-formed lymph nodes and intestinal lymphoid tissue, including Peyers patches, and human thymic epithelial cells. These mice have diverse human B cell and T cell antigen receptor repertoires and can mount mature T cell-dependent and T cell-independent antibody responses, entailing somatic hypermutation, class-switch recombination, and plasma cell and memory B cell differentiation. Upon flagellin or a Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccination, THX mice mount neutralizing antibody responses to Salmonella or severe acute respiratory syndrome coronavirus 2 Spike S1 receptor-binding domain, with blood incretion of human cytokines, including APRIL, BAFF, TGF-β, IL-4 and IFN-γ, all at physiological levels. These mice can also develop lupus autoimmunity after pristane injection. By leveraging estrogen activity to support human immune cell differentiation and maturation of antibody responses, THX mice provide a platform to study the human immune system and to develop human vaccines and therapeutics.

Background and Purpose Experimental Approach Key Results Conclusion and Implications Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL‐33 as a crucial target for the exercise‐related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF‐κB signalling pathway. Exercise inhibited NF‐κB activation by suppressing the CD14/TLR4/MyD88 and TNF‐α/TNF‐R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B‐cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF‐α, IFN‐γ, and IL‐1β, while concurrently increasing insulin expression. The qRT‐PCR results were consistent with the proteomic results.In a mouse model, exercise improved COPD and its metabolic comorbidities through immune system regulation and inflammation suppression, offering insights into potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Due to the immune‐mediated nature of non‐infectious cutaneous vasculitis, skin biopsy specimens are often submitted for direct immunofluorescence (DIF) testing when vasculitis is considered clinically. However, evidence regarding the clinical value of DIF has not been rigorously appraised.In this scoping review, we aimed to systematically evaluate the peer‐reviewed literature on the utility of DIF in vasculitis to assist with the development of appropriate use criteria by the American Society of Dermatopathology.Two electronic databases were searched for articles on DIF and vasculitis (January 1975–October 2023). Relevant case series involving more than or equal to three patients, published in English, and with full‐text availability were included. Additional articles were identified manually via reference review. Due to study heterogeneity, findings were analyzed descriptively.Of 255 articles identified, 61 met the inclusion criteria. Cumulatively representing over 1000 DIF specimens, several studies estimated DIF sensitivity to be 75%. While vascular immunoglobulin A (IgA) deposits on DIF were associated with renal disease, other systemic associations were inconsistent. Vascular IgG deposition may be overrepresented in ANCA‐associated vasculitis. Granular vascular and epidermal basement membrane zone Ig deposition differentiated hypocomplementemic from normocomplementemic urticarial vasculitis. Few studies have assessed the added value of DIF over routine microscopy alone in vasculitis.This scoping review discovered that DIF testing for vasculitis has been performed not only for diagnostic confirmation of vasculitis but also for disease subtype classification and prediction of systemic associations. Future studies on test sensitivity of DIF compared to that of histopathology are needed. [ABSTRACT FROM AUTHOR]

Summary The study of antibodies in jawed vertebrates (gnathostomes) provides every immunologist with a bird's eye view of how human immunoglobulins (Igs) came into existence and subsequently evolved into their present forms. It is a fascinating Darwinian history of conservation on the one hand and flexibility on the other, exemplified by the Ig heavy chain (H) isotypes IgM and IgD/W, respectively. The cartilaginous fish (e.g., sharks) Igs provide a glimpse of “how everything got off the ground,” while the amphibians (e.g., the model Xenopus) reveal how the adaptive immune system made an about face with the emergence of Ig isotype switching and IgG‐like structure/function. The evolution of mucosal Igs is a captivating account of malleability, convergence, and conservation, and a call to arms for future study! In between there are spellbinding chronicles of antibody evolution in each class of vertebrates and rather incredible stories of how antibodies can adapt to occupy niches, for example, single‐domain variable regions, cold‐adapted Igs, convergent mechanisms to dampen antibody function, provision of mucosal defense, and many more. The purpose here is not to provide an encyclopedic examination of antibody evolution, but rather to hit the high points and entice readers to appreciate how things “came to be.” [ABSTRACT FROM AUTHOR]

The process of stone formation in the human body remains incompletely understood, which requires clinical and laboratory studies and the formulation of a new endogenous, nanotechnological concept of the mechanism of origin and formation of crystallization centers. Previously, the mechanism of sialolithiasis was considered a congenital disease associated with the pathology of the ducts in the structure of the glands themselves. To date, such morphological changes of congenital nature can be considered from the position of the intrauterine formation of endogenous bacterial infections complicated by the migration of antigenic structures initiating the formation of crystallization centers. The present work is devoted to the study of the morphology and composition of stones obtained as a result of surgical interventions for sialolithiasis. Presumably, nanoparticles of metals and other chemical compounds can be structural components of crystallization centers or incorporated into the conditions of chronic endogenous inflammation and the composition of antigenic structures, in complexes with protein and bacterial components. X-ray microtomography, X-ray fluorescence analysis, scanning transmission electron microscopy and microanalysis, mass spectrometry, and Raman spectroscopy were used to study the pathogenesis of stone formation. Immunoglobulins (Igs) of classes A and G, as well as nanoparticles of metals Pb, Fe, Cr, and Mo, were found in the internal structure of the stones. The complex of antigenic structures was an ovoid calcified layered matrix of polyvid microbial biofilms, with the inclusion of metal nanoparticles and chemical elements, as well as immunoglobulins. The obtained results of clinical and laboratory studies allow us to broaden the view on the pathogenesis of stone formation and suggest that the occurrence of the calcification of antigenic structures may be associated with the formation of IgG4-associated disease. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The aim of this study was to determine the components and cytokine and immunoglobulin levels of koumiss during different fermentation periods, and to reveal the interrelation between these parameters. For achieving this objective, 10 samples of koumiss were prepared and randomly divided into 2 groups: the first group was sampled at 0, 1, 5, 12, and 24 h of incubation at room temperature for analysis. The second group was stored at +4°C, and samples were taken on d 5, 10, 15, and 20. The counts of Enterobacteriaceae spp., Staphylococcus , and Micrococcus spp. progressively decreased with the period of fermentation until becoming undetectable in the final samples of both groups. We fond positive or negative correlations between cytokine and immunoglobulin levels and the physicochemical and microbiological parameters in the koumiss samples in both groups. However, the levels of IFN-γ, IL-2, TNF-α, and IgG did not change significantly over time in both groups. Overall, it is clear that traditionally prepared koumiss under different fermentation times and temperatures does not show any differences in cytokine and immunoglobulin concentrations. [ABSTRACT FROM AUTHOR]

The prevalence of food allergies is on the rise, posing a significant challenge to public health. Rodents serve as the predominant animal model in food allergy research; yet, the application of rodent models proves to be a laborious and time-consuming endeavor. It is imperative to develop novel in vivo models. Ovalbumin (OVA) was administered as the allergen, following the recommended dosage used in other species. During the sensitization phase, a dosage of 0.25 mg per 10 tails per 1 L was administered twice daily, and during the challenge phase, the dosage was increased to 3 times the initial level. The study explored two dimensions of sensitization: the mode of exposure, which can be either continuous or intermittent, and the duration of exposure, which includes 3 days, 5 days, and 7 days. We examined midgut pathological changes, immunoglobulins contents, and mRNA expressions associated to T helper cells (Th) 2 cytokines following exposure. A significant 109.3 % increase in the number of eosinophils was observed in the midgut histopathology following intermittent 5-day OVA exposure, which emerged as the most effective model. OVA exposure increased concentrations of immunoglobulin M (IgM) (105.2 %), IgZ (312.1 %), and IgD (304.3 %) in this model. The mRNA expressions of Th2-related interleukin (IL)-4 and IL-13 were also elevated by 132.8 % and 421.0 %, respectively. The intermittent 5-day OVA exposure was suggested to be the best constructed zebrafish food allergy model, which may be a potential tool for research into food allergies. • Rodent food allergy models are laborious and tedious, novel models are needed. • The intermittent 5-day OVA exposure best simulates zebrafish food allergy model. • This work aims to enhance childhood health and promote sustainable aquaculture. [ABSTRACT FROM AUTHOR]

Summary Nanobodies are the products of an intriguing invention in the evolution of immunoglobulins. This invention can be traced back approximately 45 million years to the common ancestor of extant dromedaries, camels, llamas, and alpacas. Next to conventional heterotetrameric H2L2 antibodies, these camelids produce homodimeric nanobody‐based heavy chain antibodies, composed of shortened heavy chains that a lack the CH1 domain. Nanobodies against human target antigens are derived from immunized animals and/or synthetic nanobody libraries. As a robust, highly soluble, single immunoglobulin domain, a nanobody can easily be fused to another protein, for example to another nanobody and/or the hinge and constant domains of other immunoglobulins. Nanobody‐derived heavy chain antibodies hold promise as a new form of immunotherapeutics. [ABSTRACT FROM AUTHOR]

Aims: Early detection and treatment of neurodegenerative Langerhans cell histiocytosis (ND-LCH) have been suggested to prevent neurodegenerative progression. The aim of the study is to validate a standardized multidisciplinary diagnostic work-up to monitor the intravenous immunoglobulins (IVIG) treatment response and the natural course of the disease in untreated patients. Methods: Patients with abnormal somatosensory evoked potentials (SEPs) received monthly 0.5 g/kg IVIG. The diagnostic protocol included structural 3T MRI, neurological examination, brainstem auditory evoked potentials (BAEPs) and SEPs. Results: Twenty-two patients were followed for 5.2 years (median) from the first MRI evidence of ND-LCH. Eleven patients received IVIG for 1.7 years (median). At treatment start neurological examination was abnormal in 10 patients, of whom two had severe clinical impairment and four had abnormal BAEPs. At last followup, 1/11 remained stable and 7/11 improved, while worsening of neurological or neurophysiological findings, or both, occurred in 3/11. Risk factors for worsening were a severe clinical or MRI ND-LCH at treatment initiation and prolonged exposure to LCH. Of the 11 untreated patients, none improved and three worsened. Conclusions: Using a standardized diagnostic protocol, we demonstrated that IVIG treatment can lead to clinical stabilization or improvement in all paucisymptomatic patients with an MRI grading of less than 4. [ABSTRACT FROM AUTHOR]

Natural antibodies are used to compare immune systems across taxa, to study wildlife disease ecology, and as selection markers in livestock breeding. These immunoglobulins are present prior to immune stimulation. They are described as having low antigen specificity or polyreactive binding and are measured by binding to self-antigens or novel exogenous proteins. Most studies use only one or two antigens to measure natural antibodies and ignore potential effects of antigen specificity in analyses. It remains unclear how different antigen-specific natural antibodies are related or how diversity among natural antibodies may affect analyses of these immunoglobulins. Using genetically distinct lines of chickens as a model system, we tested the hypotheses that (1) antigen-specific natural antibodies are independent of each other and (2) antigen specificity affects the comparison of natural antibodies among animals. We used blood cell agglutination and enzyme-linked immunosorbent assays to measure levels of natural antibodies binding to four antigens: (i) rabbit erythrocytes, (ii) keyhole limpet hemocyanin, (iii) phytohemagglutinin, or (iv) ovalbumin. We observed that levels of antigen specific natural antibodies were not correlated. There were significant differences in levels of natural antibodies among lines of chickens, indicating genetic variation for natural antibody production. However, line distinctions were not consistent among antigen specific natural antibodies. These data show that natural antibodies are a pool of relatively distinct immunoglobulins, and that antigen specificity may affect interpretation of natural antibody function and comparative immunology. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV-71) has strong neurotropism, and it is the main pathogen causing severe hand, foot, and mouth disease (HFMD). In clinical observations, significant differences were observed in the severity and prognosis of HFMD among children who were also infected with EV-71. Genetic differences among individuals could be one of the important causes of differences in susceptibility to EV-71–induced HFMD. As P-selectin glycoprotein ligand-1 (PSGL-1) is an important receptor of EV-71, the correlation between single-nucleotide polymorphisms (SNPs) in PSGL-1 and the susceptibility to severe HFMD following EV-71 infection is worth studying. Given the role of PSGL-1 in immunity, the correlations between PSGL-1 SNPs and the immune status after EV-71 infection are also worth studying. Meanwhile, PSGL-1 variable number of tandem repeats (VNTR) represents a research hotspot in cardiovascular and cerebrovascular diseases, but PSGL-1 VNTR polymorphism has not been investigated in HFMD caused by EV-71 infection. In this study, specific gene fragments were amplified by polymerase chain reaction, and PSGL-1 VNTR sequences were genotyped using an automatic nucleic acid analyzer. The correlations of PSGL-1 VNTR polymorphism with the susceptibility to EV-71–associated severe HFMD and the post-infection immune status were analyzed. The PSGL-1 VNTR A allele was identified as a susceptible SNP for severe HFMD. The risk of severe HFMD was higher for AA + AB genotype carriers than for BB genotype carriers. The counts of peripheral blood lymphocyte subsets were lower in AA + AB genotype carries than in BB genotype carries. In conclusion, PSGL-1 VNTR polymorphism is associated with the susceptibility to EV-71–induced severe HFMD and the immune status after infection. PSGL-1 VNTR might play a certain role in the pathogenesis of severe cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Postbiotics are non-viable probiotic microorganisms, with or without their metabolites, that provide a health benefit to the host. They prevent the colonisation of pathogens by improving the gut environment for beneficial commensal bacteria. This effect reduces the incidence of digestive disorders in calves, which enhances animal growth and boosts the immune system and general health. The aim of this work was to evaluate the addition of postbiotics to dairy cow rations during the transition period on nutrient digestibility and milk productivity. The effects of two postbiotics from calving to two months of lactation were evaluated in twelve Friesian cows. The results suggest that postbiotic supplementation in late gestation and early lactation increases the voluntary intake of dry matter, with higher apparent total tract digestibility of nutrients. The inclusion of postbiotics in the dairy cow diet increases colostral immunoglobulin concentration and milk production with high fat and protein yields. The metabolites secreted by probiotics or released after their lysis are called postbiotics. They provide physiological benefits to the host, preventing the colonisation of pathogens by improving the intestinal environment for beneficial commensal bacteria, which reduces the incidence of digestive disorders and improves the immune system. The aim of this work was to evaluate the addition of postbiotics to dairy cow rations during the transition period on nutrient digestibility, composition, and milk yield. The effects of two postbiotics were evaluated in twelve Friesian cows from 30 days before calving to two months of lactation. The animals were randomly allocated to two treatment groups: control (CT) and supplemented with postbiotics (PC and PR). Feeding was ad libitum with 60/40 of forage/concentrate ratio on dry matter basis. Daily feed intake and milk production were recorded individually throughout the study. Two digestibility balances were performed, one before parturition and one after parturition. Colostrum was sampled at first milking and milk was sampled weekly. Data were analysed using a mixed mode in R software 4.4.1. The results suggest that postbiotic supplementation in late gestation and early lactation increase the voluntary intake of dry matter, especially in the PR treatment, with higher apparent total tract digestibility of dry matter, organic matter and neutral detergent fibre. Both treatments including postbiotics induced an increase in colostral immunoglobulin concentration. Milk production of cows receiving the PC treatment was the highest, with high fat and protein yields and a higher persistence of the production curve throughout the lactation. [ABSTRACT FROM AUTHOR]

Background: Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death. Methods: Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29). Results: One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 109/L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: −4.46, 34.78; P = 0.096). Conclusion: Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESsCOVID was registered prospectively at ClinicalTrials.gov on October 6, 2020.: NCT04576728 [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between the level of treponema pallidum specific antibodies （TPAb） and immunoglobulin A/E/M/G（ IgA/E/M/G） and IgG subtypes in active syphilis patients, so as to provide a basis for the comprehensive diagnosis and treatment and prognosis evaluation of clinical syphilis. Methods: Active syphilis patients admitted to the First Affiliated Hospital of Soochow University in 2023 were divided into 1∶4+ and 1∶16+ groups according to the syphilis toluidine red unheated serum test（ TRUST）, and healthy control group were selected for the detection of TPAb by chemiluminescence microparticle immunoassay（ CMIA）. The contents of IgA/E/M/G and IgG1/2/3/4 were determined by immunoturbidimetry. Results: A total of 206 patients with active syphilis （125 males and 81 females） aged （46.05±19.58） years were included in this study. Compared with the healthy control group, IgG2 was decreased and TPAb, IgA/E/M/G and IgG1/3/4 levels were increased in the active syphilis group, with statistically significant differences in TPAb, IgE and IgG1/2/3 levels（ P<0.05）. Compared with the healthy control group, TRUST 1∶4+ group had statistical differences in TPAb, IgE and IgG2, and TPAb was significantly correlated with IgE and IgG2/4. The levels of TPAb, IgA/E/M/G and IgG1/2/3 in TRUST 1∶16+ group were statistically significant, and TPAb was significantly correlated with IgE and IgG4（ P< 0.05）. In addition, there were significant differences in TPAb, IgG and IgG1/3 between the two positive groups （P<0.05）. Conclusion: The levels of TPAb and Ig in active syphilis patients with different TRUST titers are significantly different. TPAb combined with Ig can be used to monitor the strength of syphilis activity, IgA/M/G and IgG1/3 may be candidate biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: It is known that both B cells and myeloblasts from acute myeloid leukemia (AML) express immunoglobulin (Ig). However, the difference between Ig from myeloblasts and B cells has not been explored; therefore, the function and significance of AML-Ig are not well known. Here, we performed 5′ RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire of Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same AML patient, AML-Ig showed different biased V(D)J usages and mutation patterns. More importantly, mutations of AML-Ig frequently occurred at the sites of post-translational modification. In summary, our results showed that AML-Ig had different sequence characteristics than those of B-Ig and that the unique V(D)J usages of AML-Ig may serve as a novel biomarker for personalized minimal/measurable residual disease monitoring and therapeutic targets in AML patients. It is common knowledge that immunoglobulin (Ig) is produced by B lymphocytes and mainly functions as an antibody. However, it has been shown recently that myeloblasts from acute myeloid leukemia (AML) could also express Ig and that AML-Ig played a role in leukemogenesis and AML progression. The difference between Ig from myeloblasts and B cells has not been explored. Studying the characteristics of the Ig repertoire in myeloblasts and B cells will be helpful to understand the function and significance of AML-Ig. We performed 5′ RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire in myeloblasts and B cells from Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same patient, AML-Ig showed different biased V(D)J usages and mutation patterns. In addition, the CDR3 length distribution of AML-Ig was significantly different from those of B-Ig. More importantly, mutations of AML-IgH, especially Igμ, Igα, and Igδ, were different from that of B-IgH in each AML patient, and the mutations frequently occurred at the sites of post-translational modification. AML-Ig has distinct characteristics of variable regions and mutations, which may have implications for disease monitoring and personalized therapy. [ABSTRACT FROM AUTHOR]

Primary cytomegalovirus infection during pregnancy has a high risk of vertical transmission, with severe fetal sequelae mainly associated with first-trimester infections. We conducted a retrospective analysis of 200 IU/kg cytomegalovirus-specific hyperimmune globulin (HIG), used in first-trimester maternal primary infections for congenital infection prevention. The primary outcome was vertical transmission, defined as neonatal viruria or positive amniocentesis if pregnancy was discontinued. HIG, initially administered monthly and since 2019 biweekly, was discontinued in negative amniocentesis cases. Women declining amniocentesis and positive amniocentesis cases with normal sonography were offered monthly HIG until delivery as a treatment strategy. The total transmission rate was 29.9% (32/107; 10 pregnancy terminations with positive amniocentesis, 18 completed pregnancies with positive amniocentesis and 4 declining amniocentesis). Maternal viremia was the only factor associated with fetal transmission (OR 4.62, 95% CI 1.55–13.74). The transmission rate was not significantly different whether HIG was started during the first or second trimester (28.2% vs. 33.3%; p = 0.58), or between monthly and biweekly subgroups (25.7% vs. 37.8%, p = 0.193). Pre-treatment maternal viremia could inform decisions as a predictor of congenital infection. [ABSTRACT FROM AUTHOR]

Mucosal immunity is a multifaceted system of immunological responses that provides a barrier against pathogenic invasion and can be regulated by psychosocial and neuroendocrine factors. The present study aims to elucidate the association between everyday emotional states, emotion regulation skills, and mucosal immunity by utilizing an ambulatory assessment approach. 30 healthy subjects (61% male; M = 30.18 years old) completed an emotion questionnaire (PANAS) and collected saliva samples via passive drool to determine salivary immunoglobulin‐A (S‐IgA) excretion rate three times a day over a period of 1 week. In a multi‐level model, the influence of emotions on S‐IgA, both on a within‐subject and between‐subject level, was estimated. We found that most of the variation in S‐IgA (74%) was accounted for by within‐subject changes rather than stable between‐subject differences. On a within‐subject level, negative emotions had a significant positive effect on S‐IgA levels (b = 1.87, p =.015), while positive emotions had no effect. This effect of negative emotions was moderated by the individual emotion regulation skills, with higher regulation skills corresponding to smaller effects (b = −2.67, p =.046). Furthermore, S‐IgA levels decreased over the course of a day, indicating circadian rhythmicity (b = −0.13, p =.034). These results highlight the possibilities of intensive longitudinal data to investigate the covariance between psychological and immunological states over time. This article elucidates the relationship between everyday emotional states and mucosal immune function, specifically demonstrating how negative emotions are associated with increased salivary immunoglobulin‐A concentrations. Furthermore, the study provides evidence for the modulatory influence of emotion regulation skills on this association. This work not only advances the empirical understanding of the emotion–immunity interconnections but also offers potential future directions for using intensive longitudinal data in psychoneuroimmunology research. [ABSTRACT FROM AUTHOR]

Introduction: The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) quantities in patients with chronic lymphocytic leukemia (CLL) has not been extensively studied. Methods: We analyzed Ig levels in 45 stable patients with indolent CLL (without indication for treatment) and 87 patients with progressive disease before first‐line treatment. Fifty‐five patients were evaluated again after the treatment with CIT. Results: We observed significantly lower levels of all Ig classes and subclasses in patients with progressive disease compared to patients with indolent disease. After treatment, median IgA increased from 0.59 g/L to 0.74 g/L (p = 0.0031). In stable patients, lower IgA2 was associated with shorter time to first treatment, although it did not reach statistical significance (p = 0.056). Shorter overall survival was observed in patients with progressive disease and lower IgG2 (p = 0.043). Surprisingly, among the patients with progressive CLL, unmutated IGHV genes were associated with higher levels of IgG, IgG1 and IgM, while TP53 mutation and/or 17p deletion were associated with higher levels of IgA and IgA1. Conclusions: CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction. [ABSTRACT FROM AUTHOR]

The gut microbiome plays an essential role in host immune responses, including allergic reactions. However, commensal gut microbiota is extremely sensitive to antibiotics and excessive usage can cause microbial dysbiosis. Herein, we investigated how changes in the gut microbiome induced by ampicillin affected the production of IgG1 and IgG2a antibodies in mice subsequently exposed to Anisakis pegreffii antigens. Ampicillin treatment caused a notable change in the gut microbiome as shown by changes in both alpha and beta diversity indexes. In a 1-dimensional immunoblot using Anisakis-specific anti-mouse IgG1, a 56-kDa band corresponding to an unnamed Anisakis protein was detected using mass spectrometry analysis only in ampicillin-treated mice. In the Anisakis-specific anti-mouse IgG2a-probed immunoblot, a 70-kDa band corresponding to heat shock protein 70 (HSP70) was only detected in ampicillin-treated and Anisakis-immunized mice. A 2-dimensional immunoblot against Anisakis extract with immunized mouse sera demonstrated altered spot patterns in both groups. Our results showed that ampicillin treatment altered the gut microbiome composition in mice, changing the immunization response to antigens from A. pegreffii. This research could serve as a basis for developing vaccines or allergy immunotherapies against parasitic infections. [ABSTRACT FROM AUTHOR]

A 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, who had a 5/8 HLA haploidentical match. However, the patient had donor-specific antibodies against the donor's HLA-B 0702 and HLA-C 0702. To address this issue, after rituximab therapy, the patient was given platelet transfusions from B0702- and C0702-positive donors on day − 1 and day 0, and immunoglobulin on day 0, followed by PBSCT. Donor-specific antibodies decreased by over 90%, and engraftment was confirmed on day 13. Since then, the patient has remained relapse-free and healthy. This case suggests that appropriate management of donor-specific antibodies can enable safe transplantation, even in donors who test positive for these antibodies. [ABSTRACT FROM AUTHOR]

ABSTRACT: The aim of this study was to determine the components and cytokine and immunoglobulin levels of koumiss during different fermentation periods, and to reveal the interrelation between these parameters. For achieving this objective, 10 samples of koumiss were prepared and randomly divided into 2 groups: the first group was sampled at 0, 1, 5, 12, and 24 h of incubation at room temperature for analysis. The second group was stored at +4°C, and samples were taken on d 5, 10, 15, and 20. The counts of Enterobacteriaceae spp., Staphylococcus, and Micrococcus spp. progressively decreased with the period of fermentation until becoming undetectable in the final samples of both groups. We fond positive or negative correlations between cytokine and immunoglobulin levels and the physicochemical and microbiological parameters in the koumiss samples in both groups. However, the levels of IFN-γ, IL-2, TNF-α, and IgG did not change significantly over time in both groups. Overall, it is clear that traditionally prepared koumiss under different fermentation times and temperatures does not show any differences in cytokine and immunoglobulin concentrations.

Pulmonary light chain deposition disease is a rare entity characterized by immunoglobulin deposition within the lung parenchyma with pathologic features distinct from pulmonary amyloidosis. Here, the authors present the clinical presentation, associations, and radiologic features of pulmonary light chain deposition disease in a series of 4 patients as well as discuss the distinctions from amyloidosis. The present case series highlights the frequent presence of both cysts and nodules at CT. Clinically, lymphoma and/or autoimmune disease are often associated.

Abstract Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real‐world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia‐Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow‐up time of 29.5 months (interquartile range 13.3–54.3 months) were included in the analysis – 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in‐situ hybridisation status, receive first‐line myeloma treatment with immunomodulatory drugs or anti‐CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow‐up (adjusted hazard ratio 0.72, 95% CI 0.46–1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Abstract Acquired von Willebrand syndrome (AVWS) is a bleeding disorder in which an underlying condition induces a quantitative or qualitative deficiency in the von Willebrand factor. This case demonstrates the rare diagnosis of AVWS due to an Immunoglobulin G monoclonal gammopathy in an elderly woman who presented with significant gastrointestinal bleeding. Originally thought to be type 1 von Willebrand disease, this case provides a cautious example to clinicians that without a detailed history or an understanding of the associated laboratory work‐up, AVWS may be missed with potentially fatal consequences. Fortunately, AVWS was recognized and treated with intravenous immunoglobulin with a resolution of bleeding.

Abstract Background Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death. Methods Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29). Results One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (

Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.

Abstract Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence‐based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell–containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence‐based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non‐PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.

Introduction: Coronary atherosclerosis is a condition that affects the arteries supplying the heart. The soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) belongs to the immunoglobulin superfamily, and its expression is increased in vascular endothelial cells in atherosclerosis. Aim: To estimate serum sVCAM-1 in atherosclerotic Coronary Artery Disease (CAD) patients with varying severity and to look for its association with the Atherogenic Index (AI). Materials and Methods: This hospital-based cross-sectional study was carried out in the Department of Biochemistry at NEIGRIHMS, a tertiary care Institute in the northeastern part, Shillong India, for a period of one year (2019) with 68 angiographically confirmed newly diagnosed CAD patients and were divided into three groups as Single Vessel Disease (SVD), Double Vessel Disease (DVD) and Triple Vessel Disease (TVD). The following biochemical tests were performed on fasting serum samples: Glucose, lipid profiles {Total cholesterol, High Density Lipid (HDL)-C, Low Density Lipid (LDL)-C, Triglycerides (TG)}, Interleukin-6(IL-6), and sVCAM-1. The Chi-square test was used to assess the significance of the association of risk factors such as hypertension, smoking, and diabetes in the participants. One-way Analysis of Variance (ANOVA) was conducted to identify significant differences in the levels of the estimated parameters among the participant groups. Results: The average age of presentation for the study participants was 61±10.8 years. The study involved 68 recently diagnosed patients with confirmed CAD, of whom 59 (87%) were males and 9 (13%) were females. Among the total patients, 44 (65%) were smokers, 45 (66%) had hypertension, and 29 (43%) were diabetic. The Chi-square test revealed a significant association between smoking (p-value=0.015) and hypertension (p-value=0.008) with CAD, but no association was found with diabetic status. The level of serum sVCAM-1 was found to increase with the number of vessels involved. Significant differences were observed in the levels of serum cholesterol and LDL-C among the groups (TVD>DVD>SVD). The bivariate Pearson’s correlation test between Antherogenic Index (AI) and sVCAM-1 showed a statistically significant positive correlation (r=0.33, p-value=0.0059). Conclusion: Serum sVCAM-1 levels may be used for the follow-up study of patients with CAD, which could be more economical and convenient compared to {Total cholesterol, High Density Lipid (HDL)-C, Low Density Lipid (LDL)-C, Triglycerides (TG)} angiography.

Objective The object of this study was to investigate the effect of replacing soybean meal with Clostridium autoethanogenum protein (CAP) in broiler diets on growth performance, blood indicators, antioxidant capacity, and immune function. Methods A total of 180 Arbor Acres broilers were randomly divided into three treatments, each treatment with six replicates and 10 broilers per replicate for a 42-day feeding trial. The control group (CON) was fed corn-soybean meal based diet. The CAP-1 and CAP-2 groups were considered to use CAP to replace 25% or 50% of soybean meal in the diet, respectively. The average daily gain and average daily feed intake of broilers at 1 to 21 d, 22 to 42 d, and 1 to 42 d were measured, and the feed conversion ratio was calculated. At the 42nd day of age, two broilers with similar weights and fasted for 12 h were selected in each replicate for blood collection from the brachial wing vein. The blood routine indicators, serum biochemical indicators, serum antioxidant capacity, and immunoglobulin content of broiler chickens were measured. Results Replacement of soybean meal with 25% (CAP-1) and 50% (CAP-2) CAP significantly increased the average daily gain of 22 to 42 d and 1 to 42 d and decreased the average daily feed intake and feed conversion rate (p

Background/purpose: It is known that COVID-19 patients show many clinical oral symptoms due to the immunological mechanisms triggered by the virus. Aim of this study is to analyze the antibody response to SARS-CoV-2, and to evaluate the oral health status of hospitalized patients. Materials and methods: 160 patients with COVID-19 confirmed by SARS-CoV-2–specific RT-PCR testing and 160 healthy volunteers (HI) with similar age, gender and systemic status were included to compare the bio-chemical and oral manifestations. Oropharyngeal swab specimens were collected to evaluate the salivary interleukins (IL-1, IL-6, IL-10) and immunoglobulins (sIgA, sIgG, sIgM). Oral findings (DMFT, plaque index, salivary flow rate), socio-demographic information and systemic conditions were also recorded. Chi-square, Mann–Whitney U and Spearman's ratio tests were applied to determine the possible correlations between the factors (P = 0.05). Results: The mean DMFT scores of COVID-19 patients (12.71 ± 7.3) were significantly higher than the HI (7.39 ± 2.8), whereas cases of total or partial edentulism were more common among COVID-19 patients (P 0.05), salivary parameters were found statistically different (P

Abstract Background A case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children. Methods One hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC). Results The level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P

Previous studies have shown that maternal resveratrol improved growth performance and altered the microbial composition of suckling piglets under hot summer conditions. However, it remains unclear how maternal resveratrol improves growth performance of suckling piglets during high summer temperatures. A total of 20 sows (Landrace × Large White; three parity) were randomly assigned to 2 groups (with or without 300 mg/kg resveratrol) from d 75 of gestation to d 21 of lactation during high ambient temperatures (from 27 to 30 °C). The results showed that maternal resveratrol supplementation increased total daily weight gain of piglets under hot summer conditions, which is consistent with previous studies. Furthermore, we found that maternal resveratrol improved the intestinal morphology and intestinal epithelial proliferation in suckling piglets. Dietary resveratrol supplementation affected the characteristics of exosome-derived microRNAs (miRNAs) in sow colostrum, as well as the genes targeted by differentially produced miRNAs. MiRNAs are concentrated in the tight junction pathway. As a result, the expression of intestinal tight junction proteins was increased in suckling piglets (P

Introduction. When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic. Results and conclusion. The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.

Abstract It is known that maternal immunoglobulins (Igs) are transferred to the offspring across the placenta. However, receiving maternal Igs, especially before the blood–brain barrier (BBB) is formed in the offspring’s brain, carries the risk of transferring some brain-reactive Igs. It is thus hypothesized that there may be some unknown benefit to the offspring’s brain that overweighs this risk. In this study, we show that the Ig detected in the embryonic/perinatal mouse brain is IgG not produced by the pups themselves, but is basically transferred from the mother across the placenta using the neonatal Fc receptor (FcRn) during embryonic stages. The amount of IgG in the brain gradually decreases after birth, and almost disappears within 3 weeks postnatally. IgG is detected on axon bundles, microglia, and some meningeal cells, including border-associated macrophages (BAMs), endothelial cells, and fibroblasts. Using Fcer1g knock-out (KO) mice, we show that BAMs and microglia receive maternal IgG in an Fc receptor γ chain (FcRγ)-dependent manner, but IgG on other meningeal cells and axon bundles is received independently of the FcRγ. These results suggest that maternal IgG may be used in multiple ways by different mechanisms. In maternal IgG-deficient mice, the number of interneurons in the cerebral cortex is not altered around birth but is reduced postnatally, suggesting that receipt of maternal IgG is necessary for the maintenance of cortical interneurons in the postnatal period. These data suggest that maternal IgG has an important function in the developing brain, where neither obvious inflammation nor infection is observed.

Background: The morbidity and mortality from AL amyloidosis has significantly improved with the development of novel treatments. Daratumumab is a highly effective treatment for AL amyloidosis, but end-stage kidney disease is a common complication of this condition. Kidney transplantation is the ideal form of renal replacement therapy but has historically been contraindicated in this group of patients. Methods: Given the improved survival and better treatments of both conditions, we argue that it is time to reconsider transplanting these patients. Results: We report our experience of transplanting four patients with AL amyloidosis who had achieved stable remission through treatment with daratumumab. Conclusions: We highlight the key challenges involved and discuss important clinical issues for patients receiving daratumumab, particularly the difficulties with interpreting the crossmatch in light of daratumumab and immunoglobulin therapy interference. We also discuss the complexities involved in balancing the risks of infection, relapse, rejection, and immunosuppression in such patients. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder (PCSM‐LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy.Our aim was to characterize treatment options for PCSM‐LPD, with a focus on the role of radiotherapy.This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM‐LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy.All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra‐low‐dose radiotherapy (4 Gy in 1–2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids.Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra‐low‐dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS‐CoV‐2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti‐spike (S) IgG1 glycosylation patterns following SARS‐CoV‐2 vaccination in DS and healthy controls (HC). Total and anti‐Spike IgG1 Fc N‐glycan glycoprofiles were measured in non‐exposed adults with DS and controls before and after SARS‐CoV‐2 vaccination by liquid chromatography–mass spectrometry (LC–MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti‐S IgG1 with age. In contrast, anti‐S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules. [ABSTRACT FROM AUTHOR]

Objective: To study whether children with peptic ulcer would have abnormalities in cellular and humoral immune functions, and whether Helicobacter pylori (Hp) infection would affect the immune function of children with peptic ulcer. Methods: This is a retrospective study. The subjects of study were 72 children with diagnosed and cured peptic ulcer (ulcer group), and 50 healthy children with physical examination (control group) at Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University from June 2020 to December 2022. Further detection was conducted on T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) and immunoglobulin levels. Results: Of the 72 children with peptic ulcer, 53(73.6%) were positive for Hp (Hp-positive group) and 19 (26.4%) were negative (Hp-negative group). The levels of CD3+, CD4+, and CD4+/CD8+ ratio in the control group were significantly higher than those in the ulcer group, with statistically significant difference (P<0.05); while the level of IgG in the control group was lower than that in the ulcer group, with statistically significant difference (P<0.05). Meanwhile, there were statistically significant differences in that the levels of CD3+, CD4+ and CD8+ were increased in Hp-positive group than those in Hp-negative group before treatment (P<0.05); while CD4+/CD8+ ratio was lower in the former group than that in the latter group, with statistically significant difference (P<0.05). Conclusion: Hp infection can induce the elevation of T lymphocyte subsets. The development of peptic ulcer has an intimate association with the disorder of cellular and humoral immune functions. [ABSTRACT FROM AUTHOR]

Background: Massage and aromatherapy are frequently used by older adults as alternative interventions to enhance immunity and induce relaxation. This pilot study evaluated the effect of massage therapy with oil and aromatherapy alone and in combination using objective biological indices. Methods: Twenty‐eight participants recruited by convenience sampling included adults aged between 25 and 65 years (Group 1), elderly individuals over 65 years without nursing care (Group 2), and older adults over 65 needing long‐term nursing support (Group 3). A multiple‐group pretest‐post‐test design was employed, and the effect among the three groups was compared. Interventions included: (i) oil massage therapy; (ii) aromatherapy; and (iii) aroma oil massage therapy. Each therapy session lasted 5 min, with 3 min of observation before and after the session and 10 min interval between sessions. Group 3 omitted one therapy (2: aromatherapy) to reduce their physical burden. An electroencephalogram (EEG) was recorded for α, β, and θ activities of brain waves. EEG data were collected at three points: before, during, and after each treatment. Salivary secretory immunoglobulin A (s‐IgA) concentration, oxygen saturation (SPO2), and pulse rate were measured before and after each session. Results: Across all therapy modalities, there was a noticeable increase in the α wave, indicative of relaxation, during the treatment. Significant differences were observed before and during the oil massage in both Group 1 and Group 2. Aromatherapy demonstrated a significant difference before and during treatment in Group 1. Among the biological parameters, s‐IgA levels indicated no significant changes. The pulse rate decreased with oil massage. Significant differences were noted before and after therapy in all cases for SPO2 and in Group 2 for pulse rate. Conclusions: Three therapies induced EEG and physiological changes in the adult group and older adults without nursing care. However, these effects are limited in older adults requiring nursing care. [ABSTRACT FROM AUTHOR]

Background: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti‐human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. Methods: This retrospective study included adults who underwent lung‐only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA‐positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low‐level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)‐free times were compared between groups using Cox proportional hazards models. Results: Thirty‐six out of 167 eligible patients (22%) were DSA‐positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55–1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34–1.52) in DSA‐positive patients compared to patients with low‐level/negative DSAs. Incidences of antibody‐mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. Conclusion: We describe a single‐center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols. [ABSTRACT FROM AUTHOR]

Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence‐based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell–containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence‐based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non‐PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats. [ABSTRACT FROM AUTHOR]

The third complementary‐determining regions of the heavy‐chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These 'ultralong' CDR3Hs form β‐ribbon stalks that protrude from the surface of the antibody with a disulfide cross‐linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B‐cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen‐unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing. [ABSTRACT FROM AUTHOR]

Introduction: Coronary atherosclerosis is a condition that affects the arteries supplying the heart. The soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) belongs to the immunoglobulin superfamily, and its expression is increased in vascular endothelial cells in atherosclerosis. Aim: To estimate serum sVCAM-1 in atherosclerotic Coronary Artery Disease (CAD) patients with varying severity and to look for its association with the Atherogenic Index (AI). Materials and Methods: This hospital-based cross-sectional study was carried out in the Department of Biochemistry at NEIGRIHMS, a tertiary care Institute in the northeastern part, Shillong India, for a period of one year (2019) with 68 angiographically confirmed newly diagnosed CAD patients and were divided into three groups as Single Vessel Disease (SVD), Double Vessel Disease (DVD) and Triple Vessel Disease (TVD). The following biochemical tests were performed on fasting serum samples: Glucose, lipid profiles {Total cholesterol, High Density Lipid (HDL)-C, Low Density Lipid (LDL)-C, Triglycerides (TG)}, Interleukin-6(IL-6), and sVCAM-1. The Chi-square test was used to assess the significance of the association of risk factors such as hypertension, smoking, and diabetes in the participants. One-way Analysis of Variance (ANOVA) was conducted to identify significant differences in the levels of the estimated parameters among the participant groups. Results: The average age of presentation for the study participants was 61±10.8 years. The study involved 68 recently diagnosed patients with confirmed CAD, of whom 59 (87%) were males and 9 (13%) were females. Among the total patients, 44 (65%) were smokers, 45 (66%) had hypertension, and 29 (43%) were diabetic. The Chi-square test revealed a significant association between smoking (p-value=0.015) and hypertension (p-value=0.008) with CAD, but no association was found with diabetic status. The level of serum sVCAM-1 was found to increase with the number of vessels involved. Significant differences were observed in the levels of serum cholesterol and LDL-C among the groups (TVD>DVD>SVD). The bivariate Pearson’s correlation test between Antherogenic Index (AI) and sVCAM-1 showed a statistically significant positive correlation (r=0.33, p-value=0.0059). Conclusion: Serum sVCAM-1 levels may be used for the follow up study of patients with CAD, which could be more economical and convenient compared to {Total cholesterol, High Density Lipid (HDL)-C, Low Density Lipid (LDL)-C, Triglycerides (TG)} angiography. [ABSTRACT FROM AUTHOR]

Cytologic evaluation of aspirate slides from a small, <1-cm, interdigital mass on a 9-y-old, spayed female Yorkshire Terrier revealed a proliferation of discrete, round cells containing few-to-many, variably sized, round, eosinophilic, cytoplasmic inclusions. The top differentials based on the cytologic findings were either a plasma cell tumor or a B-cell lymphoma with Mott cell differentiation. The unencapsulated, well-demarcated, multilobulated round-cell neoplasm was completely excised. Immunohistochemical stains were performed to further characterize the neoplasm, which had immunolabeling for multiple myeloma oncogene 1 and vimentin, but did not react with CD3, CD20, melan A, or ionized calcium–binding adapter molecule 1, nor with a Giemsa special stain. Ultrastructurally, the cytoplasmic granules had Russell body–like morphology. A solitary, cutaneous plasmacytoma with Mott cell differentiation has not been described previously in veterinary medicine, to our knowledge. [ABSTRACT FROM AUTHOR]

It is known that COVID-19 patients show many clinical oral symptoms due to the immunological mechanisms triggered by the virus. Aim of this study is to analyze the antibody response to SARS-CoV-2, and to evaluate the oral health status of hospitalized patients. 160 patients with COVID-19 confirmed by SARS-CoV-2–specific RT-PCR testing and 160 healthy volunteers (HI) with similar age, gender and systemic status were included to compare the bio-chemical and oral manifestations. Oropharyngeal swab specimens were collected to evaluate the salivary interleukins (IL-1, IL-6, IL-10) and immunoglobulins (sIgA, sIgG, sIgM). Oral findings (DMFT, plaque index, salivary flow rate), socio-demographic information and systemic conditions were also recorded. Chi-square, Mann–Whitney U and Spearman's ratio tests were applied to determine the possible correlations between the factors (P = 0.05). The mean DMFT scores of COVID-19 patients (12.71 ± 7.3) were significantly higher than the HI (7.39 ± 2.8), whereas cases of total or partial edentulism were more common among COVID-19 patients (P < 0.05). While plaque index scores were similar for both groups (P > 0.05), salivary parameters were found statistically different (P < 0.05). Severe and moderate cases showed higher proinflammatory interleukin levels (IL-1 = 68.74 pg/ml, IL-6 = 53.31 pg/ml) amongst all (P < 0.05). While secretory immunoglobulins were almost depleted at baseline, (sIgA = 0.11 mg/ml, sIgG = 0.21 mg/ml, sIgM = 0.08 mg/ml) they reached to threshold levels after 4 weeks. Higher proinflammatory interleukin levels indicated that traces of ongoing "Cytokine Storm" in COVID-19 patients which can also be observed in oral environment. Poor oral hygiene and malnutrition due to edentulism can pave the way for having a severe COVID-19 infection. [ABSTRACT FROM AUTHOR]

Passive immunisation with normal human immunoglobulin (NHIG) is recommended as post-exposure prophylaxis (PEP) for higher-risk measles contacts where vaccination is contraindicated. However, the concentration of measles-specific antibodies in NHIG depends on antibody levels within pooled donor plasma. There are concerns that measles immunity in the Australian population may be declining over time and that blood donors' levels will progressively decrease, impacting levels required to produce effective NHIG for measles PEP. A cross-sectional study of Australian plasmapheresis donors was performed using an age-stratified, random sample of recovered serum specimens, collected between October and November 2019 (n = 1199). Measles-specific IgG antibodies were quantified by ELISA (Enzygnost anti-measles virus IgG, Siemens), and negative and equivocal specimens (n = 149) also underwent plaque reduction neutralisation testing (PRNT). Mean antibody levels (optical density values) progressively decreased from older to younger birth cohorts, from 2.09 [±0.09, 95% CI] to 0.58 [±0.04, 95% CI] in donors born in 1940–1959 and 1990–2001, respectively (p < 0.0001). This study shows that mean measles-specific IgG levels are significantly lower in younger Australian donors. While current NHIG selection policies target older donors, as younger birth cohorts become an increasingly larger proportion of contributing donors, measles-specific antibody concentrations of NHIG will progressively reduce. We therefore recommend monitoring measles-specific antibody levels in future donors and NHIG products in Australia and other countries that eliminated measles before the birth of their youngest blood donors. [ABSTRACT FROM AUTHOR]

Background and Aims: We performed a meta‐analysis of randomized controlled trials (RCTs) to summarize the overall effect of intravenous immunoglobulin (IVIG) on mortality outcomes among hospitalized coronavirus disease 2019 (COVID‐19) patients. Methods: We systematically searched electronic databases up to June 1, 2023. Pooled odds ratio (OR) of mortality with a 95% confidence interval (CI) was generated using a random‐effects model. The risk of bias was appraised using the Cochrane risk‐of‐bias Version 2 tool for randomized trials. Results: Nine RCTs were included: three RCTs had an overall low risk of bias, four RCTs had some concerns in the overall risk of bias, and two RCTs trials had an overall high risk of bias. The use of IVIG indicated a significant reduction in the odds of mortality (pooled OR = 0.69; 95% CI 0.50–0.96) relative to nonuse of IVIG. Subgroup analysis in patients with a severe course of COVID‐19 revealed no significant reduction in the odds of mortality (pooled OR = 0.58; 95% CI 0.29–1.16). Conclusions: We suggest exercising caution when interpreting effectiveness of IVIG in reducing mortality among hospitalized patients with COVID‐19. Our findings emphasize for larger trials with rigorous study designs to better understand the impact of IVIG, particularly in those with severe COVID‐19. Key points: The use of intravenous immunoglobulin (IVIG) indicated a significant reduction in the odds of mortality relative to nonuse of IVIG.Subgroup analysis in patients with a severe course of coronavirus disease 2019 (COVID‐19) revealed no significant reduction in the odds of mortality.We suggest exercising caution when interpreting the efficacy of IVIG in reducing mortality among hospitalized patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Background: A case-control study was conducted to analyze the role of cerebrospinal fluid immunoglobulin in the differential diagnosis of autoimmune encephalitis and viral encephalitis in children. Methods: One hundred and twenty patients with autoimmune encephalitis (AE) treated in our hospital from February 2021 to February 2022 were included as the observation group (AE group). 100 patients with viral encephalitis (VE group) were selected as the control group. The clinical data of all patients were collected and analyzed retrospectively. Immunoglobulin G (IgG) and immunoglobulin A (IgA)in cerebrospinal fluid of the two patients were measured by immune turbidimetry. Immunoglobulin M (IgM), and the diagnostic value of immunoglobulin in cerebrospinal fluid (CSF) in patients with AE was analyzed by receiver working curve (ROC). Results: The level of IgG in the cerebrospinal fluid of the AE group was higher than that of the VE group, and the level of IgM was lower than that of the VE group, and the difference was statistically significant (P < 0.05). There was no significant difference in IgA levels between the two groups (P > 0.05). In terms of Magnetic Resonance (MR) features, the paraventricular, hippocampal, occipital and parietal lobes were more involved in AE patients, frontal and temporal lobes were more involved in VE patients, and paraventricular and occipital lobes were involved in MS. The proportion of bilateral extensive lesions in both groups was significantly higher than 50%. The proportions of patients in the AE group involving the lateral ventricle, insula, and parietal lobes were significantly higher than those in the VE group, and the proportions involving the basal ganglia, temporal lobes, and frontal lobes were significantly lower than those in the VE group, and the differences were statistically significant (All P < 0.05). The Area Under Curve (AUC) of IgG, IgA and IgM alone in the diagnosis of AE were 0.795(0.587–0.762), 0.602(0.502–0.631) and 0.627(0.534–0.708), respectively with the sensitivity values of 81.24% and 65.608, respectively and the specificity values of 65.08%, 57.54% and 75.01% respectively. The AUC of IgA + IgM in the diagnosis of AE was 0.733(0.617–0.849), and the sensitivity and specificity are 62.58% and 75.07% respectively. The AUC of IgA + IgG in the diagnosis of AE was 0.823(0.730–0.917), and the sensitivity and specificity were 81.24% and 67.54% respectively. The AUC of IgG + IgM in the diagnosis of AE was 0.886(0.814 ~ 0.958), and the sensitivity and specificity were 84.48% and 77.59% respectively. The AUC of IgA + IgM + IgG in the diagnosis of AE was 0.924 (0.868–0.981) with the sensitivity of 93.82%, and the specificity of 77.56%. Conclusion: The level of immunoglobulin in cerebrospinal fluid can be used as an effective reference index for the diagnosis of AE. The combined detection of IgA, IgM and IgG can improve the accuracy, sensitivity and specificity of AE. [ABSTRACT FROM AUTHOR]

This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced β-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced β-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-a production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extracttreated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects. [ABSTRACT FROM AUTHOR]