Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima–media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.

NF2-related Schwannomatosis (NF2-SWN) remains a disorder with few effective treatment options. Patients develop vestibular schwannomas (VSs) on both auditory nerves, which gradually impair hearing and often result in significant communication difficulties, social withdrawal, and higher rates of depression. Progress in understanding NF2-SWN biology and translating discoveries into therapies has been slowed by the absence of robust animal models that faithfully reproduce both tumor behavior and the associated neurological deficits. In this review, we summarized the development of animal models that not only reproduce tumor growth in the peripheral nerve microenvironment but also reproduce tumor-induced neurological symptoms, such as hearing loss and ataxia. We further highlight the currently available organotypic models for NF2-SWN. Together, these systems provide an essential foundation for advancing mechanistic studies and accelerating the development of effective therapies for this devastating disorder.

Aim: Atherosclerosis and diabetes mellitus (DM) often lead to severe conditions, such as acute ischemic stroke (AIS), cardiovascular disease (CVD), and chronic kidney disease (CKD). Some cancers are also associated with atherosclerosis. Therefore, identifying novel autoantibody biomarkers associated with atherosclerosis-related conditions is crucial for improving early diagnosis and risk assessment. Methods: We used an array of 9,480 proteins to detect IgG antibodies in the serum of patients with atherosclerosis. Following this screening, we quantified the antibody levels using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) with recombinant antigen proteins. Results: Ubiquitin conjugating enzyme E2 E3 (UBE2E3) was identified as a candidate antigen recognized by IgG antibodies in the sera of individuals diagnosed with atherosclerosis. Compared with healthy donors, significantly higher serum antibody levels against UBE2E3 were found in patients with AIS, DM, CVD, CKD, esophageal cancer (EC), and gastric cancer (GC), but not in those with colorectal cancer (CRC). Receiver operating characteristic (ROC) analysis revealed that the higher areas under the ROC curves for anti-UBE2E3 antibodies were observed in DM- or nephrosclerosis-associated CKD than in the others. Spearman’s correlation analysis revealed that serum anti-UBE2E3 antibody (s-UBE2E3-Ab) levels were associated with the plaque score, maximum intima-media thickness, and cardio-ankle vascular index, which are typical indices of atherosclerosis and stenosis. In the survival analysis of GC and CRC, patients who were s-UBE2E3-Ab-positive had significantly poorer prognoses than patients who were s-UBE2E3-Ab-negative. The difference became more prominent when s-UBE2E3-Abs were combined with anti-differential screening-selected gene aberrant in neuroblastoma antibody (DAN-Ab) or sclerostin domain-containing protein 1 (SOSTDC1), which are bone morphogenetic protein (BMP) antagonists. Conclusions: The s-UBE2E3-Ab marker is highly associated with atherosclerosis-related diseases, such as AIS, CVD, DM, CKD, and digestive tract cancers, suggesting the involvement of BMP signals.

Dipeptidyl peptidase-4 (DPP4) is involved in immune regulation and metabolic homeostasis. Although DPP4 inhibitors are widely used in type 2 diabetes, the clinical relevance of autoantibodies against DPP4 (DPP4-Ab) remains unclear. In this study, we aimed to investigate the association between circulating DPP4-Ab levels and mortality in 274 patients with type 2 diabetes (mean age, 63 years). Serum DPP4-Ab levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), and survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression analysis. During a mean follow-up of approximately 5 years, 32 deaths had occurred. Patients with elevated DPP4-Ab titers (>1,676.8 alpha counts) had a higher mortality rate than those with low titers (22.2% vs. 9.3%, p = 0.0177). In Cox proportional hazards regression analysis, DPP4-Ab titers showed a trend toward association with all-cause mortality when analyzed as a continuous variable per 100 alpha counts (a.c.) increase (hazard ratio [HR], 1.042; 95% confidence interval [CI], 0.996–1.090; p = 0.071). When patients were stratified using the predefined cutoff value of 1,676.8 a.c., the high DPP4-Ab group showed significantly higher mortality risk than the low DPP4-Ab group (HR, 2.30; 95% CI, 1.09–4.84; p = 0.028). Addition of DPP4-Ab to an age-based model only slightly improved predictive discrimination. These findings suggest that elevated DPP4-Ab titers may be associated with mortality risk; however, this association should be interpreted cautiously and warrants further investigation as a potential adjunctive immunometabolic biomarker in type 2 diabetes.