Serum Levels Of Autoantibodies Research Articles

IL-6 receptor antibody treatment improves muscle weakness in experimental autoimmune myasthenia gravis mouse model.

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG.

Ginseng-Epimedii formula ameliorated experimental Sjögren’s syndrome via reducing IL-6 production

Medicinal herbs have been recently investigated to explore their therapeutic potential on autoimmune disorders, as an alternative treatment to relieve disease symptoms. Here, we sought to determine the immunomodulatory function of a Chinese medicine formula Ginseng-Epimedii (GE), constituted by Lycium barbarum, Ginseng, Eleutherococcus senticosus and Epimedium brevicornum, on mice with experimental Sjögren’s syndrome (ESS). We found that GE-treated ESS mice exhibited improved salivary gland function and decreased serum levels of autoantibodies. In line with the network pharmacology analysis, GE treatment suppressed IL-6 production by B cells and conventional dendritic cells, associated with decreased effector T cell subsets. Using co-culture assay and adoptive transfer model, we demonstrated that splenoctyes from ESS mice receiving GE treatment showed impaired capacity to drive pathogenic Th17 and T follicular helper cell differentiation. Thus, this study suggested the therapeutic potential of GE formula in treating SS, by skewing the microenvironment that unfavored effector T cell responses.

Rutin alleviates lupus nephritis by inhibiting T cell oxidative stress through PPARγ

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology. In vitro experiments indicated that Rutin's therapeutic effect on LN is linked to its significant reduction of oxidative stress in T cells. Further investigations suggest that Rutin enhances oxidative stress management through the modulation of Peroxisome proliferator-activated receptor gamma (PPARγ). We observed that Rutin modulates PPARγ activity, leading to reduced transcriptional activity of NF-κB and STAT3, which in turn inhibits the secretion of inflammatory cytokines such as IL-6, TNF-α, and IL-17.In summary, Rutin can exert an antioxidant effect by regulating PPARγ and shows therapeutic action against LN.

Autoantibodies against acetylcholine receptors are increased in archived serum samples from patients with schizophrenia

Previous studies have demonstrated that the levels of IgG against neurotransmitter receptors are increased in patients with schizophrenia. Genome-wide association (GWA) studies of schizophrenia confirmed that 108 loci harbouring over 300 genes were associated with schizophrenia. Although the functional implications of genetic variants are unclear, theoretical functional alterations of these genes could be replicated by the presence of autoantibodies. This study examined the levels of plasma IgG antibodies against four neurotransmitter receptors, CHRM4, GRM3, CHRNA4 and CHRNA5, using an in-house ELISA in 247 patients with schizophrenia and 344 non-psychiatric controls. Four peptides were designed based on in silico analysis with computational prediction of HLA-DRB1 restricted and B-cell epitopes. The relationship between plasma IgG levels and psychiatric symptoms, as defined by the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT), were examined. The results showed that the levels of plasma IgG against peptides derived from CHRM4 and CHRNA4 were significantly increased in patients with schizophrenia compared with control subjects, but there was no significant association of plasma IgG levels with any symptom domain or any specific symptoms. These preliminary results suggest that CHRM4 and CHRNA4 may be novel targets for autoantibody responses in schizophrenia, although the pathogenic relationship between increased serum autoantibody levels and schizophrenia symptoms remains unclear.

The role of GaD65, ZNTS, IA-2, and IAA as predictive biomarkers for type 1 diabetes mellitus in children

Background Type 1 diabetes mellitus (T1DM) is a chronic disorder characterized by immune-mediated harm to the pancreatic β-cells that produce insulin. The four major autoantibodies implicated in the pathophysiology are insulin autoantibodies, glutamic acid decarboxylase antibodies, tyrosine phosphatase antibodies, and zinc transporter 8 antibodies. Objective We examined whether children with T1DM have particular antibodies related to T1DM and their association with clinical features. Materials and methods The study involved 60 Iraqi children who had been diagnosed with T1DM within the last 3 years, as well as a control group of 60 healthy individuals without diabetes or autoimmune diseases. Blood samples were collected from all participants to analyze the levels of serum autoantibodies, specifically insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase (IA-2A), and zinc transporter 8 (ZnT8A), using an enzyme-linked immunosorbent assay (Sandwich-ELISA). Results and conclusion The findings revealed that a significant number of patients with diabetes had elevated levels of antibodies against zinc transporter 8 (P<0.001), tyrosine phosphatase (P<0.001), insulin autoantibodies (P<0.001), and glutamic acid decarboxylase (P<0.001). Glutamic acid decarboxylase 65 antibodies were found to be the most prevalent. All four biomarkers showed remarkable effectiveness in distinguishing positive and negative cases. Logistic regression analysis revealed that glutamic acid decarboxylase 65 and insulin antibodies were significantly associated with the outcome, while tyrosine phosphatase and zinc transporter 8 did not show such a relationship. These findings indicate that measurements of anti-zinc transporter 8, tyrosine phosphatase, insulin autoantibodies, and glutamic acid decarboxylase could be important diagnostic markers for identifying patients with T1DM, aiding in early detection and understanding the disease process.

Proteomics-Based Identification of Potential Therapeutic Targets of Artesunate in a Lupus Nephritis MRL/lpr Mouse Model.

This study aimed to identify potential therapeutic targets of artesunate in an MRL/lpr lupus nephritis mouse model by quantitative proteomics. We detected serum autoimmune markers and proteinuria in 40 female mice that were divided into 4 groups (n = 10): normal C57BL/6 control group; untreated MRL/lpr lupus; 9 mg/kg/day prednisone positive control MRL/lpr lupus; and 15 mg/kg/day artesunate-treated MRL/lpr lupus groups. Renal pathology in the untreated MRL/lpr lupus and artesunate groups was examined by Periodic acid-Schiff (PAS) staining. Artesunate treatment in lupus mice decreased serum autoantibody levels and proteinuria while alleviating lupus nephritis pathology. Through tandem mass tag-tandem mass spectrometry (TMT-MS/MS) analyses, differentially expressed proteins were identified in the artesunate group, and subsequent functional prediction suggested associations with antigen presentation, apoptosis, and immune regulation. Data are available via ProteomeXchange with the identifier PXD046815. Parallel reaction monitoring (PRM) analysis of the top 19 selected proteins confirmed the TMT-MS/MS results. Immunohistochemistry, immunofluorescence, and Western blotting of an enriched protein from PRM analysis, cathepsin S, linked to antigen presentation, highlighted its upregulation in the untreated MRL/lpr lupus group and downregulation following artesunate treatment. This study suggests that artesunate holds potential as a therapeutic agent for lupus nephritis, with cathepsin S identified as a potential target.

Effects of autoimmune abnormalities on fertility and placental morphology in mice

Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in AID-prone MRL/MpJ-Faslpr/lpr mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-Faslpr/lpr at five months and defined as moLpr and moMpJ, respectively. AID indices (spleen weight and serum autoantibody levels) and fertility status (number and size of fetuses, morphology, and comprehensive gene expression of placentas) were evaluated on gestational day 15.5. Both strains showed equivalent fertility, but moLpr showed lighter placentas and fetuses than moMpJ, and decreased fertility with AID severity. moLpr placentas had a higher number of T cells, higher expression of genes associated with T helper 2 and T follicular helper functions, and altered expression of genes (Krt15, Slc7a3, Sprr2a3) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (Ccl5, Cxcl9) was significantly increased in moLpr placentas, and CCL5 and CXCL9 were detected in moLpr placentas, particularly in T cells and placenta-component cells, respectively. Thus, AID altered placental morphofunction and fertility in mice; however, fertility was maintained at the examined time points. This study enhances our understanding of placental alterations and gestational risk due to AIDs.

Effect of low and high doses of vitamin D3 therapy on vitamin D3, antithyroid antibody and thyroid hormone levels in thyroid autoimmunity

Aims: Vitamin D3 deficiency is more common in autoimmune thyroid diseases (AITD). Vitamin D3 supplementation in AITD is not questioned, but the required doses have been offered differently in several reports. This study attempts to provide a clinical answer as to what doses of vitamin D3 may be effective in AITD. Methods: Ninety-seven patients were included in the study: 44 with Hashimoto’s thyroiditis (HT), 26 with Graves ’disease (GD) and 27 controls. Serum vitamin D3, thyroid hormone and autoantibody levels against thyroid peroxidase (TPO) and TSH receptor were measured before and after treatment. Biochemical data were measured by a fully automated competitive chemiluminescence assay and presented as geometric mean(95% confidence interval). Results: Baseline vitamin D3 deficiency was detected in 22 out of 44 HT, 13 out of 26 GD and 19 out of 27 controls, and improved after vitamin D3 therapy. Vitamin D3 therapy significantly increased serum vitamin D3 levels in all patient groups [46.07(16.55-128.29) vs. 71.05(40.61-124.3) nmol/l, p<0.0001 for HT, 44.27(8.98-218.25) vs. 64.22(38.85-106.16) nmol/l, p<0.0207 for GD, and 39(15.57-97.73) vs. 59.32(27.27-129.03) nmol/l, p<0.0003 for controls]. The increass in vitamin D3 levels was found after low-dose vitamin D3 therapy (<7000 NE/week) in HT (p<0.0001) and controls (p<0.0002), but not in GD. The success of vitamin D3 therapy was dependent on high doses of vitamin D3 (>7000 NE/week) in GD, but levels were lower in Graves’ ophthalmopathy (p<0.0302). Anti-TPO antibody and TSH levels were decreased by low doses of vitamin D3 in HT, but FT4 and FT3 decreased, and TSH levels increased only by high doses in GD. Conclusion: The efficacy of vitamin D3 therapy was demonstrated in all patient groups. The greatest improvement in vitamin D3 status was seen in HT. A dose-dependency of vitamin D3 therapy was rather related to the improvement in GD.

Age-Related Decline in Brain Myelination: Quantitative Macromolecular Proton Fraction Mapping, T2-FLAIR Hyperintensity Volume, and Anti-Myelin Antibodies Seven Years Apart.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33-60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Specific serum autoantibodies predict the development and progression of Alzheimer’s disease with high accuracy

AbstractBackgroundAutoimmunity plays a key role in the pathogenesis of Alzheimer’s disease (AD); however, whether autoantibodies in peripheral blood can be used as biomarkers has not been reported.MethodSerum samples were obtained from 767, 146, and 255 patients with AD, mild cognitive impairment (MCI), and other neurodegenerative diseases, respectively, and 518 healthy controls. Specific autoantibodies were measured using a custom‐made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states.ResultSeven candidate AD‐specific autoantibodies were identified, and a classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out‐performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001).ConclusionAD onset and progression are associated with an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

Investigation of anti-neuronal antibodies and disparity in central hypersomnias

Study objectivesMicrobial antigens can elicit an immune response leading to the production of autoantibodies cross-reacting with autoantigens. Still, their clinical significance in human sera in the context of brain diseases is unclear. Therefore, assessment of natural autoantibodies reacting with their neuropeptides may elucidate the autoimmune etiology of central hypersomnias. The study aims to determine whether serum autoantibody levels differ in patients with different types of central hypersomnias (narcolepsy type 1 and 2, NT1 and NT2; idiopathic hypersomnia, IH) and healthy controls and if the differences could suggest the participation of autoantibodies in disease pathogenesis. MethodsSera from 91 patients with NT1, 27 with NT2, 46 with IH, and 50 healthy controls were examined for autoantibodies against assorted neuropeptides. Participants were screened using questionnaires related to sleep disorders, quality of life, and mental health conditions. In addition, serum biochemical parameters and biomarkers of microbial penetration through the intestinal wall were determined. ResultsA higher prevalence of autoantibodies against neuropeptides was observed only for alpha-melanocytes-stimulating hormone (α-MSH) and neuropeptide glutamic acid-isoleucine (NEI), which differed slightly among diagnoses. Patients with both types of narcolepsy exhibited signs of microbial translocation through the gut barrier. According to the questionnaires, patients diagnosed with NT2 or IH had subjectively worse life quality than patients with NT1. Patients displayed significantly lower levels of bilirubin and creatinine and slightly higher alkaline phosphatase values than healthy controls. ConclusionsOverall, serum anti-neuronal antibodies prevalence is rare, suggesting that their participation in the pathophysiology of concerned sleep disorders is insignificant. Moreover, their levels vary slightly between diagnoses indicating no major diagnostic significance.

Specific serum autoantibodies predict the development and progression of Alzheimer’s disease with high accuracy

Autoimmunity plays a key role in the pathogenesis of Alzheimer’s disease (AD). However, whether autoantibodies in peripheral blood can be used as biomarkers for AD has been elusive. Serum samples were obtained from 1,686 participants, including 767 with AD, 146 with mild cognitive impairment (MCI), 255 with other neurodegenerative diseases, and 518 healthy controls. Specific autoantibodies were measured using a custom-made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states. As a result, seven candidate AD-specific autoantibodies were identified, including MAPT, DNAJC8, KDM4D, SERF1A, CDKN1A, AGER, and ASXL1. A classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out-performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001). This study indicated that AD onset and progression are possibly accompanied by an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

Physiological Changes in the Levels of Anti-Cytokine Autoantibodies in Early Pregnancy Are Missing in Pregnant Women with Hashimoto's Thyroiditis.

T helper type 1 (Th1) and inflammatory cytokines play essential roles in early pregnancy and also in the pathogenesis of Hashimoto's thyroiditis (HT). Changes in the serum level of autoantibodies to cytokines, which may be able to modulate their availability and actions have been described in several autoimmune disorders. Yet, no data are available on anti-cytokine autoantibodies either during early pregnancy or in patients with HT. The aim of the study was to measure autoantibodies to inflammatory-, Th1- and Th22-cytokines in serum samples in healthy pregnancy (HP) and in pregnant women with HT (HTP). As pathological autoantibodies are hallmarks of HT, in addition we also measured anti-B-cell activator factor (BAFF) autoantibodies. The measurement was carried out with a Luminex multiplex assay and the Luminex MAGPIX Instrument, age-matched healthy women (HC) and women with HT (HT) were used as controls. In the first trimester of HP, anti-TNFα, anti-IL-8, and anti-IFNγ autoantibodies were significantly decreased, while autoantibodies to BAFF were significantly elevated compared to the HC. However, these alterations were not present in the HTP. Moreover, the levels of autoantibodies to IL-22 and TNFα were significantly increased in HTP compared to the HP. All differences in the levels of the investigated autoantibodies could be detected in the first trimester of pregnancies except for anti-IL-22 autoantibodies. According to our results we can conclude that alterations in the levels of autoantibodies to inflammatory and Th1 cytokines are physiological in the first trimester of pregnancy and their disturbance can be associated with autoimmune conditions such as HT.

Cerebrospinal fluid biomarkers in psychiatric autoimmune encephalitis: a retrospective cohort study.

Psychiatric autoimmune encephalitis (pAE) is a growing field of interest in diagnosis and therapy in psychiatric hospitals and institutions. This study investigates the relevant extent to which there are potential biomarkers in cerebrospinal fluid (CSF) that can differentiate against a cohort with neurodegenerative disease. We included in this study a total of 27 patients with possible and definite psychiatric autoimmune encephalitis and compared with a cohort with CSF-based AD (n = 27) different biomarkers in CSF such as lactate, cell count, % lymphocytes, % monocytes, total protein content, albumin, immunoglobulins G (IgG), M (IgM) and A (IgA), CSF/serum albumin ratio, CSF/serum IgG ratio, CSF/serum IgA ratio, intrathecal IgG synthesis, blood-brain barrier disruption, specific antibody synthesis for measles, rubella, herpes simplex virus, varicella zoster virus, Ebstein-Barr virus and cytomegalovirus, total tau protein (t-tau), phosphorylated tau protein 181 (p-tau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40) and the amyloid beta 42/ amyloid beta 40 (Aß42/40) ratio. The p-tau 181 was elevated above cut-off values in both possible pAE and AD. However, in definitive pAE, p-tau181 levels were not elevated. When elevated p-tau181 levels in possible AE were compared with those in AD, we found relevant differences, such as a relative increase in p-tau181 in AD patients. Elevated p-tau181 levels were detected in possible psychiatric AEs with IgLON5, glycine, recoverin, titin, and nonspecific neuropil antibodies in serum and IgLON5, titin, Yo, and nonspecific neuropil autoantibodies in CSF. In addition, we detected elevated levels of p-tau181 and IgLON5 autoantibodies in serum and CSF, and Yo autoantibodies in CSF in patients with definitive pAE. Interestingly, we observed a higher CSF/serum IgM ratio in possible and definitive pAE than in AD patients. Our results suggest that neuroaxonal brain damage may occur in specific psychiatric AEs associated with IgLON5, glycine, recoverin, and titin autoantibodies. Further research should focus on the CSF/serum IgM ratio as an early marker of autoantibody production in pAE compared to AD as a potential biomarker for differential diagnosis.

β-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. β-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether β-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and β-arrestin2 knockout (Arrb2 KO) mice, and the experimentsidentified that liver β-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, β-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. β-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that β-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas β-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, β-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3β pathway. These results suggest that β-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, β-arrestin2 may act as an effective therapeutic target for AIH.

A quinazoline derivative suppresses B cell hyper-activation and ameliorates the severity of systemic lupus erythematosus in mice.

Background: Aberrant autoreactive B cell responses contribute to the pathogenesis of systemic lupus erythematosus (SLE). Currently, there is no safe and effective drug for intervention of SLE. Quinazoline derivative (N4-(4-phenoxyphenethyl)quinazoline-4,6-diamine, QNZ) is a NF-κB inhibitor and has potent anti-inflammatory activity. However, it is unclear whether QNZ treatment can modulate B cell activation and SLE severity. Methods: Splenic CD19+ B cells were treated with QNZ (2, 10, or 50nM) or paeoniflorin (200μM, a positive control), and their activation and antigen presentation function-related molecule expression were examined by flow cytometry. MRL/lpr lupus-prone mice were randomized and treated intraperitoneally with vehicle alone, 0.2mg/kg/d QNZ or 1mg/kg/d FK-506 (tacrolimus, a positive control) for 8weeks. Their body weights and clinical symptoms were measured and the frequency of different subsets of splenic and lymph node activated B cells were quantified by flow cytometry. The degrees of kidney inflammation and glycogen deposition were examined by hematoxylin and eosin (H&E) and PAS staining. The levels of serum autoantibodies and renal IgG, complement C3 deposition were examined by ELISA and immunofluorescence. Results: QNZ treatment significantly inhibited the activation and antigen presentation-related molecule expression of B cells in vitro. Similarly, treatment with QNZ significantly mitigated the SLE activity by reducing the frequency of activated B cells and plasma cells in MRL/lpr mice. Conclusion: QNZ treatment ameliorated the severity of SLE in MRL/lpr mice, which may be associated with inhibiting B cell activation, and plasma cell formation. QNZ may be an excellent candidate for the treatment of SLE and other autoimmune diseases.

Does the Association of Hashimoto's Thyroiditis with Differentiated Thyroid Cancer Really Have a Protective Role?

The study is an investigation of aggressive tumor features, prognosis, and disease-specific mortality rates of differentiated thyroid cancer (DTC) in the presence of concomitant Hashimoto's Thyroiditis (HT). The data of patients with DTC followed in our tertiary care center between 2000-2022 were analyzed. Variables such as patient age, gender, preoperative serum autoantibody levels, tumor characteristics, and treatment modalities were obtained from medical records. The diagnosis of HT was based either on the presence of a positive result in the pathological examination and/or on antibody positivity. A total of 637 patients [mean±SD age, 44.9±13.5 years; 485 women [76.1%)] were included in the analysis. The overall prevalence of coexistent HT was 22.9% (n=146). The disease-specific mortality associated with DTC was 2.9%. DTC patients with HT compared to those without; have more positive lymphovascular invasion (p<0.001), and lymph node metastases (p<0.001). According to the Kaplan-Meier curves, disease-specific survival rates among DTC patients without HT were significantly higher than patients with HT (log-rank p=0.002). The disease-specific mortality rate was 4.79% in DTC patients with HT, it was 1.43% in those without HT. Hashimoto thyroiditis was not associated with a 10-year recurrence-free survival (p=0.059). Differentiated thyroid cancers with concomitant HT are associated with some aggressive tumor features (such as lymphovascular invasion and nodal metastasis) and lower survival. In staging systems based on tumor risk factors, it may be useful to evaluate the presence of concomitant HT as a prognostic factor.

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with 'Actionable' Pulmonary Nodules.

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology's Lung Imaging and Reporting Data System (Lung-RADS) 80-90% of patients screened will have clinically "non-actionable" nodules (Lung-RADS 1 or 2), and those harboring larger, clinically "actionable" nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

Possible autoimmune mechanisms of regulation of rat behavior in the “open field” test

BACKGROUND: In recent years, researchers have demonstrated interest in the autoimmune mechanisms of regulation of physiological processes. In response to damage or protein expression, the levels of autoantibodies increased to ensure the restoration of the disturbed balance. Levels of autoantibodies are high in many diseases.&#x0D; AIM: The aim of this study was to assess the levels of autoantibodies in the blood serum of experimental animals and evaluate their behavior in the open field test.&#x0D; MATERIALS AND METHODS: Of 32 male rats, two groups were formed: group 1 was not exposed to stress, whereas group 2 was subjected to stress for 7 days by applying a clamp on the skin fold for 15 min daily. Three days after the last stress procedure, testing was conducted in the open field. After assessing the behavior, blood serum was obtained, and the levels of autoantibodies to dopamine receptors (DR1 and DR2) and NMDA receptors (NR1, NR2A, and NR2B) were determined.&#x0D; RESULTS: Compared with group 1, group 2 visited the central zones of the field less often, had lower vertical activity, and less often performed acts of washing. In group 2, the levels of autoantibodies to DR1 and DR2 were higher, but to NR2B were lower. Correlation analysis revealed that in group 2, the level of autoantibodies to DR2 was associated with horizontal activity (r = 0.60). In group 1, a relationship was established between the level of autoantibodies to NR2B and the number of runs through the central zones of the field (r = +0.68).&#x0D; CONCLUSIONS: Taking into account the revealed relationship between the levels of autoantibodies and activity in the open field, the degree of increase in blood IgG titers to DR2 receptors may reflect the severity of changes in the behaviors of animals under stress. Conversely, in connection with the emerging data on the possibility of IgG penetration through the bloodbrain barrier, the effect of autoantibodies on brain dopamine receptors with a limited activity of the dopaminergic system may be considered.

Changes in Clinical Activity, Serum Autoantibody Levels, and Chorioretinal Vessels After Systemic Glucocorticoid Therapy in Thyroid Eye Disease.

The aim of this study was to investigate changes in the Clinical Activity Score, serum thyroid-stimulating hormone receptor antibody and thyroid-stimulating immunoglobulin levels, chorioretinal blood vessels, and extraocular muscle thickness in patients with thyroid eye disease following systemic steroid treatment. This prospective observational study enrolled 57 patients with active thyroid eye disease who received systemic intravenous glucocorticoids for 12weeks. Demographics, clinical activity scores, optical coherence tomography images, and serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were assessed at baseline, at 6 and 12weeks after intravenous (IV) GC therapy initiation, and 2months after IV GC therapy termination. The extraocular muscle thickness, choroidal thickness, and choroidal vascularity index were measured. The clinical activity scores showed a significant decrease. Serum thyroid-stimulating immunoglobulin levels dropped continuously for 2months. The thyroid-stimulating hormone receptor antibody level decreased until 12weeks after treatment but returned to within the normal range in 75% of patients after 77 and 126days, respectively. The choroidal thickness decreased at all time points. The thickness of the medial and inferior rectus muscles decreased at 2months after treatment. The clinical activity score decreased to < 3 points in 50% of patients after 78days. Intravenous glucocorticoid therapy improved the clinical activity score, chorioretinal blood flow, and extraocular muscle thickness. The serum autoantibody levels were normalized in patients with active thyroid eye disease 2 months after IV GC termination. The serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels correlated with restoration of chorioretinal capillary perfusion and improved clinical symptoms and muscle thickness. Non-invasive optical coherence tomography findings and serologic factors predict the response to intravenous glucocorticoid therapy.