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An up-to-date overview of determinants of serum immunoglobulins in adults is pivotal for clinical practice and research, but currently lacking. We therefore performed a systematic review and meta-analysis to identify determinants of serum immunoglobulin levels. Embase, Web of Science, Medline, Cochrane, and Google Scholar were searched from inception to July 11 , 2019 for articles reporting on determinants of serum immunoglobulin A, G or M (IgA, IgG or IgM) in adult humans. Random and fixed effect models were applied to obtain pooled mean differences (MDs) and 95% confidence intervals (CIs) for the association of age and sex with serum immunoglobulins. We retrieved 117 articles reporting on determinants of serum immunoglobulins, of which 28 could be meta-analyzed. Older compared to younger individuals had higher IgA (MD: 0.38; CI: 0.18 - 0.58), but lower IgM levels (MD: -0.40; 95%: -0.66 - -0.14). Men had higher IgA (MD: 0.22; CI: 0.03 - 0.42), but lower IgM levels (MD: -0.21; CI: -0.32 - -0.10) than women. Age and sex did not influence IgG. Caucasian ethnicity was associated with lower IgA, IgG, and IgM. Smoking and corticosteroid use were associated with lower IgG. Positive associations were reported of probiotics with IgG, alcohol with IgA, hypertension with IgA and IgG, and acute psychological stress with IgA, IgG, and IgM. Older age and male sex are associated with higher IgA, but lower IgM, and urge investigation of age- and sex-specific reference ranges of immunoglobulins. Other identified determinants were ethnicity, diet, lifestyle and cardio-metabolic factors.

Children 4 to 11 months of age who were at high risk for development of peanut allergy were assigned to consumption or avoidance of peanuts until 60 months of age. Peanut allergy was more than five times as likely to develop in children assigned to peanut avoidance. The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, reaching rates of 1.4 to 3.0%, 1 – 3 and peanut allergy is becoming apparent in Africa and Asia. 4 , 5 This allergy is the leading cause of anaphylaxis and death due to food allergy and imposes substantial psychosocial and economic burdens on patients and their families. 6 Peanut allergy develops early in life and is rarely outgrown. 7 – 9 Clinical practice guidelines from the United Kingdom in 1998 9 and from the United States in 2000 10 recommended the exclusion of allergenic foods from the diets of infants at . . .

Rapid increases in cases of COVID-19 were observed in multiple cities in Iran towards the start of the pandemic. However, the true infection rate remains unknown. We aimed to assess the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 18 cities of Iran as an indicator of the infection rate. In this population-based cross-sectional study, we randomly selected and invited study participants from the general population (from lists of people registered with the Iranian electronic health record system or health-care centres) and a high-risk population of individuals likely to have close social contact with SARS-CoV-2-infected individuals through their occupation (from employee lists provided by relevant agencies or companies, such as supermarket chains) across 18 cities in 17 Iranian provinces. Participants were asked questions on their demographic characteristics, medical history, recent COVID-19-related symptoms, and COVID-19-related exposures. Iran Food and Drug Administration-approved Pishtaz Teb SARS-CoV-2 ELISA kits were used to detect SARS-CoV-2-specific IgG and IgM antibodies in blood samples from participants. Seroprevalence was estimated on the basis of ELISA test results and adjusted for population weighting (by age, sex, and city population size) and test performance (according to our independent validation of sensitivity and specificity). From 9181 individuals who were initially contacted between April 17 and June 2, 2020, 243 individuals refused to provide blood samples and 36 did not provide demographic information and were excluded from the analysis. Among the 8902 individuals included in the analysis, 5372 had occupations with a high risk of exposure to SARS-CoV-2 and 3530 were recruited from the general population. The overall population weight-adjusted and test performance-adjusted prevalence of antibody seropositivity in the general population was 17·1% (95% CI 14·6–19·5), implying that 4 265 542 (95% CI 3 659 043–4 887 078) individuals from the 18 cities included were infected by the end of April, 2020. The adjusted seroprevalence of SARS-CoV-2-specific antibodies varied greatly by city, with the highest estimates found in Rasht (72·6% [53·9–92·8]) and Qom (58·5% [37·2–83·9]). The overall population weight-adjusted and test performance-adjusted seroprevalence in the high-risk population was 20·0% (18·5–21·7) and showed little variation between the occupations included. Seroprevalence is likely to be much higher than the reported prevalence of COVID-19 based on confirmed COVID-19 cases in Iran. Despite high seroprevalence in a few cities, a large proportion of the population is still uninfected. The potential shortcomings of current public health policies should therefore be identified to prevent future epidemic waves in Iran. Iranian Ministry of Health and Medical Education. For the Farsi translation of the abstract see Supplementary Materials section.

Free light chain (FLC) quantification is the most analytically sensitive blood-based method commercially available to diagnose and monitor patients with plasma cell disorders (PCDs). However, instead of directly detecting monoclonal FLCs (mFLCs), FLC assays indirectly assess clonality based on quantifying κ and λ FLCs and determination of the к/λ FLC ratio. Often an abnormal FLC ratio is the only indication of a PCD, and confirmation by a direct method increases diagnostic confidence. The aim of this study was to develop an analytically sensitive method for direct detection of mFLCs. Patient sera (n = 167) previously assessed by nephelometric FLC quantification and immunofixation electrophoresis (IFE) were affinity enriched for IgG, IgA, and total and free κ and λ light chains and subjected to MALDI-TOF MS. Relative analytical sensitivity of these methods was determined using serially diluted sera containing mFLCs. In sera with abnormal FLC ratios (n = 127), 43% of monoclonal proteins were confirmed by IFE, 57% by MALDI-TOF MS without FLC enrichment, and 87% with FLC enrichment MALDI-TOF MS. In sera with normal FLC ratios (n = 40), the FLC MALDI-TOF MS method identified 1 patient with an mFLC. Serial dilution and analysis of mFLC containing sera by IFE, nephelometry, and FLC MALDI-TOF MS demonstrated that FLC MALDI-TOF MS analysis had the highest analytical sensitivity. FLC immunoenrichment coupled to MALDI-TOF MS enables direct detection of mFLCs and significantly increases the confirmation of abnormal serum FLC ratios over IFE and MALDI-TOF MS without FLC enrichment, thereby providing added confidence for diagnosing FLC PCDs.

A previous trial showed that early consumption of peanuts resulted in fewer cases of allergy than did avoidance. In a follow-up study, all participants avoided peanuts from 5 to 6 years of age; those who had eaten peanuts in early life retained the ability to do so. Peanut allergy is a common and potentially life-threatening food allergy for which prevention and treatment strategies are required. 1 – 5 The Learning Early about Peanut Allergy (LEAP) trial showed that among infants at high risk for allergy, the sustained consumption of peanut, beginning in the first 11 months of life, resulted in an 81% lower rate of peanut allergy at 60 months of age than the rate among children who avoided peanuts. 6 , 7 In a study of oral immunotherapy to hen’s egg white, although children achieved unresponsiveness to an oral food challenge with egg, the majority had a reversion to egg . . .

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children ( n  = 89), adults ( n  = 98), elderly ( n  = 57), and COVID-19 patients ( n  = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics. Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Tuberculosis (TB) is a major global health problem and the only currently-licensed vaccine, BCG, is inadequate. Many TB vaccine candidates are designed to be given as a boost to BCG; an understanding of the BCG-induced immune response is therefore critical, and the opportunity to relate this to circumstances where BCG does confer protection may direct the design of more efficacious vaccines. While the T cell response to BCG vaccination has been well-characterized, there is a paucity of literature on the humoral response. We demonstrate BCG vaccine-mediated induction of specific antibodies in different human populations and macaque species which represent important preclinical models for TB vaccine development. We observe a strong correlation between antibody titers in serum versus plasma with modestly higher titers in serum. We also report for the first time the rapid and transient induction of antibody-secreting plasmablasts following BCG vaccination, together with a robust and durable memory B cell response in humans. Finally, we demonstrate a functional role for BCG vaccine-induced specific antibodies in opsonizing mycobacteria and enhancing macrophage phagocytosis in vitro , which may contribute to the BCG vaccine-mediated control of mycobacterial growth observed. Taken together, our findings indicate that the humoral immune response in the context of BCG vaccination merits further attention to determine whether TB vaccine candidates could benefit from the induction of humoral as well as cellular immunity.

Allergic reactions occur when IgE molecules become crosslinked by antigens such as food proteins. Here we create the ‘AllerScan’ programmable phage display system to characterize the binding specificities of anti-allergen IgG and IgE antibodies in serum against thousands of allergenic proteins from hundreds of organisms at peptide resolution. Using AllerScan, we identify robust anti-wheat IgE reactivities in wheat allergic individuals but not in wheat-sensitized individuals. Meanwhile, a key wheat epitope in alpha purothionin elicits dominant IgE responses among allergic patients, and frequent IgG responses among sensitized and non-allergic patients. A double-blind, placebo-controlled trial shows that alpha purothionin reactivity, among others, is strongly modulated by oral immunotherapy in tolerized individuals. AllerScan may thus serve as a high-throughput platform for unbiased analysis of anti-allergen antibody specificities. A diverse array of antigens can trigger allergic reactions. Here the authors present the ‘AllerScan’ programmable phage display library, which is an efficient and unbiased approach for profiling anti-allergen antibody reactivities at cohort scale, with which a key wheat epitope is found to distinguish between wheat allergy and tolerance.

•Prebiotic intake improved and changed immunologic indicators and intestinal microbiota structure in colorectal patients in the perioperative period.•Prebiotics increased the abundance of some commensal microbiota containing opportunistic pathogens in CRC patients.•Surgical stress decreased the abundance of most intestinal microbiota in the intestinal tract but increased the abundance of some opportunistic pathogens and commensals microbiota.•Bacteroides is a relevant bacteria for further research on the mechanism with prebiotics. The aim of the present study was to investigate the effects of prebiotics (containing fructooligosaccharides, xylooligosaccharides, polydextrose, and resistant dextrin) intake on immune function and intestinal microbiota structure in perioperative patients with colorectal cancer (CRC). A randomized, double-blind, no-treatment parallel control clinical trial involving 140 perioperative patients (90 men and 50 women, aged 40–75 y) with CRC was performed. Patients were randomly divided into two groups: an intervention group (prebiotic group, n = 70) that received prebiotic supplementation of 30 g/d for 7 d, and a control group (non-prebiotic group, n = 70) that received no prebiotic supplementation. The nutritional and immunologic indices were evaluated for both groups before and after operation and analyzed against baseline values. Moreover, fecal samples were collected from 40 patients randomly chosen from the two groups to study intestinal microbiota, which was analyzed by sequencing the V3–V4 region of 16S ribosomal DNA using the Illumina (San Diego, CA) MiSeq (PE 2 × 300 bp) platform. Oral intake of prebiotics produced significant effects on immunologic indices in both the preoperative and postoperative periods, but the patterns of effects were different. In the preoperative period, prebiotics increased serum levels of immunoglobulin G (IgG; P = 0.02), IgM (P = 0.00), and transferrin (P = 0.027; all P < 0.05). In the postoperative period, enhanced levels of IgG (P = 0.003), IgA (P = 0.007), suppressor/cytotoxic T cells (CD3+CD8+; P = 0.043), and total B lymphocytes (CD19+; P = 0.012) were identified in the prebiotic group (all P < 0.05). The differences in the intestinal microbiota at the phylum level were not statistically significant between the intervention and control groups (P > 0.05). At the genus level, prebiotics increased the abundance of Bifidobacterium (P = 0.017) and Enterococcus (P = 0.02; both P < 0.05) but decreased the abundance of Bacteroides (P = 0.04) in the preoperative period (all P < 0.05). In the postoperative period, the abundance of Bacteroides (P = 0.04) was decreased, but the abundance of Enterococcus (P = 0.00), Bacillus (P = 0.01), Lactococcus (P = 0.00), and Streptococcus (P = 0.037) increased in the non-prebiotic group (all P < 0.05); however, no significant change was identified in the abundance of Enterococcus (P = 0.56), Lactococcus (P = 0.07), and Streptococcus (P = 0.56) as a result of prebiotic intervention in this period (all P > 0.05). The abundance of Escherichia-Shigella was increased after prebiotic intake in the postoperative period (P = 0.014, P < 0.05). There was a notable trend of decline in the abundance of intestinal microbiota from preoperative to postoperative in the non-prebiotic group. Prebiotic intake is recommended to improve serum immunologic indicators in patients with CRC 7 d before operation. Prebiotics improved the abundance of four commensal microbiota containing opportunistic pathogens in patients with CRC. Surgical stress decreased the abundance of most intestinal microbiota in the intestinal tract but increased the abundance of some opportunistic pathogens and commensal microbiota. Bacteroides is a relevant bacterial species for further research on the mechanism of prebiotics.

Polyethylene glycol (PEG) is a stabilizing polymer that may act as an immunogen, as some individuals produce antibodies against it and its covalent attachment to active proteins. We wanted to determine if different titers of PEG antibodies are detected in sera from subjects before and after the SARS-CoV-2 pandemic peak, and if these antibodies possibly contribute to autoimmunity. Using ELISA, we measured IgG, IgM, IgA and IgE antibodies against different sizes of PEG, Moderna COVID-19 vaccine ingredients, and phosphatidylcholine in sera from 90 healthy adults purchased in 2018 that were negative for SARS-CoV-2 IgG antibody, and sera from 90 blood donors purchased in 2023 (collected mid-August 2023) that tested positive for SARS-CoV-2 IgG. To find possible reactivity with human tissue, we also applied both polyclonal and monoclonal antibodies raised in mouse/rabbit specifically against PEG-5K to 65 different human tissue antigens. Analysis of data showed that at 3SD above the mean of the negative control, significant elevations in IgG and IgM antibodies were detected against different sizes of PEG, vaccine ingredients, and phosphatidylcholine. For IgE, significant elevations were found in the PEG-specific antibodies. For IgA antibodies, significant elevation was found only against phosphatidylcholine. The application of monoclonal and polyclonal antibodies made against PEG to 65 different human tissue antigens showed reactions with 20 out of 65 different antigens for rabbit polyclonal, 7 out of 65 for rabbit monoclonal, and 6 out of 65 for mouse monoclonal anti-PEG antibody. Administration of PEGylated products may result in the production of PEG-specific antibodies that may contribute to autoimmunity.