Maternal IgA2 Recognizes Similar Fractions of Colostrum and Fecal Neonatal Microbiota

Microbiota acquired during labor and through the first days of life contributes to the newborn’s immune maturation and development. Mother provides probiotics and prebiotics factors through colostrum and maternal milk to shape the first neonatal microbiota. Previous works have reported that immunoglobulin A (IgA) secreted in colostrum is coating a fraction of maternal microbiota. Thus, to better characterize this IgA-microbiota association, we used flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in human colostrum and neonatal feces. We identified IgA bound bacteria (IgA+) and characterized their diversity and composition shared in colostrum fractions and neonatal fecal bacteria. We found that IgA2 is mainly associated with Bifidobacterium, Pseudomonas, Lactobacillus, and Paracoccus, among other genera shared in colostrum and neonatal fecal samples. We found that metabolic pathways related to epithelial adhesion and carbohydrate consumption are enriched within the IgA2+ fecal microbiota. The association of IgA2 with specific bacteria could be explained because these antibodies recognize common antigens expressed on the surface of these bacterial genera. Our data suggest a preferential targeting of commensal bacteria by IgA2, revealing a possible function of maternal IgA2 in the shaping of the fecal microbial composition in the neonate during the first days of life.

Pathological changes and antigen localization in the small intestine of rabbits infected with Eimeria magna

<p>Coccidiosis is a major disease caused by various <em>Eimeria</em> species in rabbits. The aim of the present study was to investigate the haematological and pathological changes in rabbits infected with <em>E. magna</em>. Moreover, the localisation of coccidial antigens was examined in the intestines of rabbits with two kinds of serum as primary antibodies. In the present study, forty-five 28-day-old weaned rabbits were randomly divided into three groups and reared in three separate places. Group A was infected with 20×10³ sporulated oocysts of <em>E. magna</em>, group B was only used to produce anti-<em>E. intestinalis</em> serum by infecting them with 3×10³ sporulated oocysts of <em>E. intestinalis</em>, and group C was designated as the control group. According to histopathological evaluation of group A, the epithelial cells of the jejunum and ileum were parasitised with a large number of oocysts and other stages of <em>E. magna</em>. The haematological results showed that red blood cell counts, haemoglobin counts, haematocrit levels and the percentage of lymphocytes were significantly decreased in group A compared with group C (<em>P</em>&lt;0.01), but white blood cell counts and the percentage of neutrophils were significantly increased (<em>P</em>&lt;0.01). The weight of group A began to decrease on the 5^th day after infection, and this decrease continued until the 9th day. Immunohistochemistry staining revealed that two kinds of coccidial antigens were basically located at the same sites of the intestine when anti-<em>E. intestinalis</em> serum and anti-<em>E. magna</em> serum were used as primary antibodies. Most likely, <em>E. magna</em> and <em>E. intestinalis</em> antigens have some similar antigenic determinants; this finding provides a theoretical basis for screening for common antigens of these two coccidian species.</p>

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

Thyroid-Associated Ophthalmopathy after Radioactive Iodine Therapy for Metastatic Follicular Thyroid Carcinoma

Thyroid-associated ophthalmopathy (TAO) is an inflammation of the extraocular muscles and periorbital connective tissue caused by autoantibodies against common antigens to both the thyroid and orbit. The release of antigens and induction of hypothyroidism caused by radioactive iodine (RAI) therapy may exacerbate TAO. Here, we present the case of a 67-year-old-woman treated with RAI therapy for metastatic follicular thyroid carcinoma who presented with TAO during the course of sorafenib administration. Tg and TgAb levels were gradually decreased with sorafenib and lenvatinib treatment, and TAO was improved without any ophthalmologic treatment.

Prospecting Biomarkers for Diagnostic and Therapeutic Approaches in Pythiosis

Pythiosis, whose etiological agent is the oomycete Pythium insidiosum, is a life-threatening disease that occurs mainly in tropical and subtropical countries, affecting several animal species. It is frequently found in horses in Brazil and humans in Thailand. The disease is difficult to diagnose because the pathogen’s hyphae are often misdiagnosed as mucoromycete fungi in histological sections. Additionally, there is no specific antigen to use for rapid diagnosis, the availability of which could improve the prognosis in different animal species. In this scenario, we investigated which P. insidiosum antigens are recognized by circulating antibodies in horses and humans with pythiosis from Brazil and Thailand, respectively, using 2D immunoblotting followed by mass spectrometry for the identification of antigens. We identified 23 protein spots, 14 recognized by pooled serum from horses and humans. Seven antigens were commonly recognized by both species, such as the heat-shock cognate 70 KDa protein, the heat-shock 70 KDa protein, glucan 1,3-beta-glucosidase, fructose-bisphosphate aldolase, serine/threonine-protein phosphatase, aconitate hydratase, and 14-3-3 protein epsilon. These results demonstrate that there are common antigens recognized by the immune responses of horses and humans, and these antigens may be studied as biomarkers for improving diagnosis and treatment.

Maternal IgA2 Association with Colostrum Microbiota Contributes to Bacteria Establishment During Intestinal Colonization in the Neonate.

Background: Microbiota colonization during labor and through the first meals contributes to immune maturation and development of the newborn. Mother provides probiotics and prebiotics factors through colostrum and maternal milk to shape the first neonatal microbiota. Previous works have reported that immunoglobulin A (IgA) secreted in colostrum is coating a fraction of maternal microbiota. Methods: Thus, to better characterize the IgA-associated microbiota, we used flow cytometry coupled with 16S rDNA gene sequencing (IgA-Seq) in human colostrum and neonatal feces. We identified IgA-bound bacteria (IgA+) and characterized its diversity to elucidate possible role of IgA subclasses during neonatal bacterial colonization of the colon.Results: We found that IgA2 in the colostrum has an active role during microbiota colonization. Colostrum IgA2 is mainly associated with Bifidobacterium, Lactobacillus, and Bacteroidetes genera. This association seems to give these bacteria an advantage during their establishment since metabolic pathways related to epithelial adhesion and carbohydrate consumption are enriched within fecal IgA2+ microbiota. Association with specific bacteria could be explained since IgA2 recognizes common antigens expressed on surfaces among bacteria genera.Conclusions: Our data suggest a specific targeting of commensal bacteria by IgA2 revealing a specialized function of IgA microbiota association during neonatal intestinal colonization during the first days of life.

Vaccines for human fungal diseases: close but still a long way to go

Despite the substantial global burden of human fungal infections, there are no approved fungal vaccines to protect at risk individuals. Here, we review the progress that has been made and the challenges that lie ahead in the quest towards efficacious fungal vaccines. In mouse studies, protection has been achieved with vaccines directed against fungal pathogens, including species of Candida, Cryptococcus, and Aspergillus, that most commonly cause life-threatening human disease. Encouraging results have been obtained with vaccines composed of live-attenuated and killed fungi, crude extracts, recombinant subunit formulations, and nucleic acid vaccines. Novel adjuvants that instruct the immune system to mount the types of protective responses needed to fight mycotic infections are under development. Candidate vaccines include those that target common antigens expressed on multiple genera of fungi thereby protecting against a broad range of mycoses. Encouragingly, three vaccines have reached human clinical trials. Still, formidable obstacles must be overcome before we will have fungal vaccines licensed for human use.

Autoimmune anti-DNA antibodies predict disease severity in COVID-19 patients

COVID-19 can lead to severe disease and death, however the mechanisms of pathogenesis in these patients remain poorly understood. High levels of autoimmune antibodies have been observed frequently in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remain unknown.We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA.High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 41%) of patients. Anti-DNA antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 89.5% and accounting for 22% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size.Anti-DNA autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as a predictive biomarker for disease severity and specific clinical manifestations.

The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors

The enthusiasm for immune checkpoint inhibitors (ICIs), an efficient tumor treatment model different from traditional treatment, is based on their unprecedented antitumor effect, but the occurrence of immune-related adverse events (irAEs) is an obstacle to the prospect of ICI treatment. IrAEs are a discrete toxicity caused by the nonspecific activation of the immune system and can affect almost all tissues and organs. Currently, research on biomarkers mainly focuses on the gastrointestinal tract, endocrine system, skin and lung. Several potential hypotheses concentrate on the overactivation of the immune system, excessive release of inflammatory cytokines, elevated levels of pre-existing autoantibodies, and presence of common antigens between tumors and normal tissues. This review lists the current biomarkers that might predict irAEs and their possible mechanisms for both nonspecific and organ-specific biomarkers. However, the prediction of irAEs remains a major clinical challenge to screen and identify patients who are susceptible to irAEs and likely to benefit from ICIs.