Journal of Immunology Research

Background. Although the biological functions of Forkhead box protein M1 (FOXM1) were explored in a variety of cancer, to date, however, little attention has been paid to the situation of FOXM1 in EC endometrial cancer (EC). Method. Bioinformatics analysis, including GEPIA, TIMER, cBioPortal, LinkedOmics, and STRING were used to analyze the FOXM1 gene expression, genetic alteration, and immune cell infiltration in EC. IHC staining, qPCR, cell viability, and migration assay were applied to identify the functions of FOXM1 in EC. Results. FOXM1 was highly expressed in EC tissues and closely correlated with the prognosis of EC patients. FOXM1 knockdown inhibited EC cell proliferation and invasion as well as migration. FOXM1 genetic alteration was verified in EC patients. Coexpression network of FOXM1 indicated that it had roles in the EC cell cycle and the infiltration of immune cells in EC. Furthermore, bioinformatic and immunohistochemical analysis indicated that FOXM1 induced the increased CD276 expression and also enhanced the neutrophil recruitment in EC. Conclusion. Our present study discovered a novel role of FOXM1 in EC, suggesting FOXM1 could be treated as a potential prognostic biomarker and immunotherapeutic target in EC diagnosis and treatment.

Background. The long-term prognosis of gastric cancer (GC) remains poor due to postoperative recurrence and metastasis. The increasing evidence show that the lymph node ratio (LNR) serves as an independent prognostic factor in patients with GC. In this study, we aimed to develop a prognostic signature for GC based on LNR. Methods. Survival analysis was conducted by comparing low- and high-LNR groups according to the optimal cutoff value of LNR, which was identified by receiver operating characteristic (ROC) curve analysis. Then, we identified the differentially expressed genes (DEGs) related to LNR in the training cohort of GC. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression were performed to construct the risk score signature. We then evaluated the risk score signature from the viewpoints of survival, clinic-pathological characteristics, tumor microenvironment (TME), tumor mutation burden (TMB), and immunotherapeutic and chemotherapeutic efficacy. Results. High LNR was significantly correlated with poorer prognosis and was an independent predictor of recurrence in patients with GC. Then, an eleven-gene signature that could predict the prognosis of GC patients was developed based on LNR-related DEGs in the training cohort, and the results were further confirmed in external independent cohort. In addition, the high-risk group showed aggressive clinicopathological characteristics, specific TME status, low TMB, and low immunotherapeutic sensitivity. Conclusions. The present study constructed an eleven-gene prognostic signature based on LNR to predict the prognosis of patients with GC and facilitate the development of individualized treatment strategy.

Circulating antieosinophil antibodies (AEOSA) have been associated with various autoimmune conditions affecting the liver, kidneys, lungs, and joints but are not part of routine clinical diagnostics. While analyzing human sera for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) on granulocytes, 0.8% of analyzed samples were found to be reactive with eosinophils. Our aim was to determine the diagnostic relevance and antigenic specificity of AEOSA. AEOSA were seen either in combination with an myeloperoxidase (MPO)-positive p-ANCA (44%; AEOSA+/ANCA+) or on their own (56%; AEOSA+/ANCA−). AEOSA/ANCA positivity was seen in patients with thyroid disease (44%) or vasculitis (31%), while AEOSA+/ANCA− pattern was more common in patients with autoimmune disorders of the gastrointestinal tract and/or liver. Eosinophil peroxidase (EPX) was the main target recognized in 66% of the AEOSA+ sera by enzyme-linked immunosorbent assay (ELISA). Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) were also identified as target antigens but less frequently and only in combination with EPX. In conclusion, we confirmed that EPX is a major target of AEOSA, illustrating the high antigenic potential of EPX. Our results also demonstrate the presence of concomitant AEOSA/ANCA positivity in a defined patient group. Further research should aim to elucidate the association of AEOSA with autoimmunity.

Background. Cow’s milk allergy (CMA) is the most common food allergy in early childhood. Children with CMA require a precise and punctual diagnosis. Oral food challenge (OFC) is the gold-standard procedure for diagnosing allergies, but it is laborious and requires a particular setting. The aim of the study was to identify the cutoff value of serum allergen-specific IgE values able to predict a positive response to OFC. Methods. Children with suspected CMA performed OFC with cow’s milk (CM) or derivatives. Total IgE and specific IgE to raw CM, α-lactalbumin, β-lactoglobulin, and casein were measured. Results. Seventy-two children performed OFC, and 30 (41.6%) had a positive response. The significant predictive factors were sensitization to raw CM extract (), α-lactalbumin (), β-lactoglobulin (), and casein (). The cutoff was, respectively: 5.13 kUA/L for raw CM, 1.47 for α-lactalbumin, 1.35 for β-lactoglobulin, and 4.87 for casein. Conclusions. This study allowed us to define a set of cutoff values for CM protein-specific IgE. However, these cutoffs should be interpreted not as a diagnostic tool for CMA but only predictive of response to OFC in a specific territory. Thus, the practical message may be that a value above the cutoff allows a good approximation to identify children to be started on OFC.

Background. Immune response plays a crucial role in virus clearance during COVID-19 infection and underpins vaccine efficacy. Herein, we aimed to assess the immune response during COVID-19 infection and following SARS-CoV-2 vaccination. Methods. In this retrospective study, 94 confirmed COVID-19 patients admitted to the intensive care unit were categorized into unvaccinated patients (n = 50), including 33 deceased and 17 discharged patients, and vaccinated group (n = 44) with 26 deceased and 18 discharged patients. Records of patients with severe COVID-19 admitted to the ICU between March, 2021 and March, 2022 were gathered and analyzed. Result. The assessment of immune cell counts revealed a large rise of neutrophils associated to decrease number of lymphocytes in patients with COVID-19 infection. In dead patients, we detected a significant correlation between neutrophils and inflammatory parameters such as IL-6 and CRP. Moreover, analysis of immune cell count following vaccination did not reveal any significant difference. However, the most substantial result, herein, detected is the decrease level of IL-6 in vaccinated patients as compared to unvaccinated. The reduce level of IL-6 following vaccination is observed in discharged patients as compared to deceased. Regarding the level of mortality after vaccination, we showed that all patients who received the first dose were died (46.1%, n = 12) as compared to those who have received two doses (34.6%, n = 9) and the third dose of vaccine (19.23%, n = 3) (). Strikingly, studying the inflammatory parameters after each vaccine dose, we revealed a significant decrease of IL-6 level after the booster dose (third dose), especially in vaccinated discharged patients. Conclusions. Neutrophils combined with IL-6 and CRP can be very useful markers to predict disease severity in patients admitted to ICU. The decrease level of IL-6 in vaccinated group pointed out the impact of vaccination to prevent inflammatory cytokine release.

Background. Inflammation is closely associated with the pathogenesis of various ocular diseases. Uveitis is a condition characterized by the inflammation of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and may eventually lead to blindness. The pharmacological functions of morroniside, isolated from Cornus officinalis, are multifarious. Morroniside exerts various therapeutic effects, e.g., it ameliorates inflammation. However, the specific anti-inflammatory effect of morroniside on lipopolysaccharide-induced uveitis has not been reported widely. In this study, we investigated the anti-inflammatory effect of morroniside on uveitis in mice. Methods. An endotoxin-induced uveitis (EIU) mouse model was constructed and treated with morroniside. The inflammatory response was observed using slit lamp microscopy, and histopathological changes were observed by hematoxylin–eosin staining. The cell count in the aqueous humor was measured using a hemocytometer. The concentrations of TNF-α, IL-6, and IL-1β in the ciliary body and retina were measured using ELISA kits. The expression of iNOS and Arg-1 in the ciliary body and retina was measured by immunofluorescence costaining, and western blotting was performed to measure the protein expression of JAK2, p-JAK2, STAT3, and p-STAT3 in the ciliary body and retina. Results. Morroniside effectively ameliorated the inflammatory response in EIU mice. Furthermore, morroniside significantly reduced the concentrations of IL-1β, IL-6, and TNF-α in the ciliary body and retina. Morroniside treatment significantly reduced the expression of iNOS in the ciliary body and retinal tissues. It also significantly inhibited p-JAK2 and p-STAT3 expression and promoted Arg-1 expression. In addition, morroniside boosted the effect of JAK inhibitors on the above indices. Conclusions. Collectively, these findings suggest that morroniside may protect against LPS-induced inflammation in uveitis by promoting M2 polarization through the inhibition of the JAK/STAT pathway.