Elevated Levels Of Autoantibodies Research Articles

Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival.

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis groupcompared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19.

Increased serum interferon activity in sarcoidosis compared to that in tuberculosis: Implication for diagnosis?

ObjectivesIn this study, we measured serum interferon (IFN) levels and activity in patients with sarcoidosis and tuberculosis (TB) with and without uveitis. We aimed to understand the role of IFN in the pathophysiology of both conditions and explore its potential as a discriminating marker for these clinically similar diseases. MethodsSera from an Indonesian TB and a Dutch sarcoidosis cohort were used in the analysis. IFNα2 and IFNγ concentrations were measured using Simoa® and Luminex assays, respectively. Serum IFN activity was assessed by incubating THP-1 cells with patient serum and measuring IFN-stimulated gene transcription using qPCR. Anti-IFNα2 and IFNγ autoantibodies were detected via Luminex assay and tested for neutralizing capacity using a flow cytometry-based signal transducer and activator of transcription (STAT) 1 phosphorylation inhibition assay. ResultsIFNα2 was detected in 74 % and 64 % of patients with sarcoidosis and pulmonary TB, respectively, while IFNγ was found in 78 % and 23 % of patients with sarcoidosis and TB, respectively. For uveitis cases specifically, IFNα2 was detected in 85 % of sarcoid uveitis (SU) and 33 % of tubercular uveitis (TBU) cases. Similarly, IFNγ was detected in 69 % of SU and 17 % of TBU cases. IFNγ serum concentrations were higher in sarcoidosis than that in TB patients (p < 0.0001). Focusing on patients with uveitis, SU showed increased IFNα2 (p = 0.004) and IFNγ (p < 0.002) serum concentrations compared to that in TBU. Notably, TBU displayed significantly reduced IFNα2 concentrations compared to that in healthy controls (p = 0.006). These results align with the increased interferon stimulated gene (ISG) transcriptional upregulation observed in THP-1 cells stimulated with serum from patients with sarcoidosis. Elevated levels of non-neutralizing anti-IFN autoantibodies were observed in patients with TB; however, these levels were similar to those observed in geographically matched healthy Indonesian controls. ConclusionOur results suggest decreased serum levels and activity of type I and II IFN in TB compared to those in sarcoidosis. This is indicative of distinct pathophysiological processes in these highly clinically similar diseases. We propose that the assessment of serum IFN levels and IFN activity has the potential to distinguish between sarcoidosis/SU and TB/TBU.

Pathology Deterioration in a Pure β-zero Thalassemia Heterozygote After mRNA COVID-19 Vaccination: A Case Report and Literature Review

Background: β-thalassemia heterozygotes produce sensitive levels of fetal hemoglobin and hemoglobin A2 to remain asymptomatic for life compared to β-thalassemia intermedia and β-thalassemia major patients. The asymptomatic β0 thalassemia minor individuals rarely deteriorate to the point of requiring a blood transfusion. Case report: An asymptomatic individual with a pure β0-thalassemia trait, after his first and only Pfizer modified mRNA COVID-19 injection, immediately developed cardiological, neurological, and other clinically important symptoms. The patient’s severe physical impairments resembled a presyncope (about to feint) syndrome. Multiple hematological tests prior to and after the Pfizer injection revealed that the patient sustained a medically important rise in fetal hemoglobin and concurrently a remarkable drop of his hemoglobin A2 levels, compared to prior to mRNA injection. Moreover, the alterations in his life sustaining fetal hemoglobin and hemoglobin A2 levels was accompanied by a clinically significant lowering of blood hemoglobin concentration that required blood transfusion. The patient’s antibody response to the spike protein remains very high (&gt; 10,000 AU/ml) even almost three years after the Pfizer injection. Furthermore, the elevated levels of C-reactive protein — through May 2024 — after the mRNA injection, apart from pointing to multi-organ systemic inflammation, are consistent with his elevated levels of anti-p53 autoantibodies. Conclusions: The simultaneous decrease of patient blood hemoglobin levels was consistent with the hematological readings of mean corpuscular volume, hematocrit, ferritin, folate, and zinc level deteriorations soon after the mRNA injection, which, apart from his double digit rise in C-reactive protein, resemble overall the pathological manifestations of a β-thalassemia worsening condition. By performing an investigative literature review we conclude that an autoimmune hematological disorder contributed to the patient’s severe hematological stress.

Role of T cell-induced autoimmune response in the pathogenesis of glaucoma.

This review aims to elucidate the role of T cell-induced autoimmune responses in the pathogenesis of glaucoma, focusing on the immunological changes contributing to retinal ganglion cell (RGC) damage. A comprehensive review of recent studies examining immunological mechanisms in glaucoma was conducted. This included analyses of T cell interactions, heat shock proteins (HSPs), and resultant autoimmune responses. Key findings from experimental models and clinical observations were synthesized to present a coherent understanding of immune dynamics in glaucoma. Glaucoma is a neurodegenerative disease marked by optic nerve atrophy and irreversible vision loss due to RGC damage. The disease is etiologically heterogeneous, with multiple risk factors and pathogenic mechanisms. Recent research highlights the dual immunomodulatory role of T cells in immune protection and injury. T cells, pre-sensitized by bacterial HSPs, can cross-react with endogenous HSPs in RGCs under stress, leading to autoimmune damage. Elevated levels of HSP autoantibodies and abnormal T cell activity have been observed in glaucoma patients, indicating a significant autoimmune component in disease progression. T cell-induced autoimmune responses are crucial in the pathogenesis of glaucoma, contributing to RGC degeneration beyond the effects of elevated intraocular pressure. Understanding these immunological mechanisms is vital for developing targeted neuroprotective therapies for glaucoma.

Notch1 hyperactivity drives ubiquitination of NOX2 and dysfunction of CD8+ regulatory T cells in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) display heightened immune activation and elevated IgG autoantibody levels, indicating compromised regulatory T cell (Tregs) function. Our recent findings pinpoint CD8+ Tregs as crucial regulators within secondary lymphoid organs, operating in a NOX2-dependent mechanism. However, the specific involvement of CD8+ Tregs in SLE pathogenesis and the mechanisms underlying their role remain uncertain. SLE and healthy individuals were enlisted to assess the quantity and efficacy of Tregs. CD8+CD45RA+CCR7+ Tregs were generated ex vivo, and their suppressive capability was gauged by measuring pZAP70 levels in targeted T cells. Notch1 activity was evaluated by examining activated Notch1 and HES1, with manipulation of Notch1 accomplished with Notch inhibitor DAPT, Notch1 shRNA, and Notch1-ICD. To create humanized SLE chimeras, immune-deficient NSG mice were engrafted with PBMCs from SLE patients. We observed a reduced frequency and impaired functionality of CD8+ Tregs in SLE patients. There was a downregulation of NOX2 in CD8+ Tregs from SLE patients, leading to a dysfunction. Mechanistically, the reduction of NOX2 in SLE CD8+ Tregs occurred at a post-translational level rather than at the transcriptional level. SLE CD8+ Tregs exhibited heightened Notch1 activity, resulting in increased expression of STUB1, an E3 ubiquitin ligase that binds to NOX2 and facilitates its ubiquitination. Consequently, restoring NOX2 levels and inhibiting Notch1 activity could alleviate the severity of the disease in humanized SLE chimeras. Notch1 is the cell-intrinsic mechanism underlying NOX2 deficiency and CD8+ Treg dysfunction, serving as a therapeutic target for clinical management of SLE.

Hereditary periodic fevers in children

Fevers in children is a pressing challenge in paediatrics, as they are one of the most common symptoms people seek medical help. Autoinflammatory diseases (AIDs) constitute a group of diseases, where fever is one of the main symptoms, and fever attacks have a certain frequency and duration. Autoinflammatory diseases are rooted in the systemic aseptic inflammation associated with activation of the innate immune system, without elevated levels of autoantibodies. The most common autoinflammatory diseases include hereditary periodic fevers, among which are familial Mediterranean fever (FMF), HIDS/MKD, CAPS-, TRAPS-syndromes and rarer diseases (deficiency of natural interleukin receptor antagonists). The pathogenesis of this group of diseases is based on the process of accelerated formation of a supramolecular protein complex (inflammasome), which subsequently leads to the transition of the inactive form of IL1β into its active form. The clinical presentations of these diseases may be similar and include episodes of fever, abdominal pain, arthralgia, various rashes, etc., as well as an increase in acute phase parameters. These diseases are characterized by symptoms at certain intervals; they usually have intervals without showing any symptoms. Familial Mediterranean fever is characterized by a certain ethnic background (Armenians, Turks, Arabs, Jews). Today, molecular genetic testing is the most accurate method for diagnosing familial Mediterranean fever. Current therapy aims to prevent attacks of the disease, but it is also important to use symptomatic therapy to relieve the child’s condition when an attack has already developed. Modern treatment strategies include both drugs that have long been used in paediatric practice (colchicine, non-steroidal anti-inflammatory drugs (ibuprofen), glucocorticosteroids) and novel genetically engineered biological drugs (interleukin antagonists and tumour necrosis factor inhibitors, etc.).

Hashimoto’s Encephalopathy Presenting as Dizziness and Diplopia

Hashimoto’s encephalopathy (HE) is an uncommon neurological disorder characterized by subacute encephalopathy with elevated serum levels of thyroid autoantibodies. Due to the absence of specific tests and the diversity of neurological symptoms and signs, the diagnosis of HE is often delayed. We highlight the various manifestations of HE by reporting a patient who presented with atypical neurological signs such as dizziness and diplopia. The diagnosis was delayed until the patient progressed to cognitive impairment and generalized chorea.

Hashimoto’s Encephalopathy Presenting as Dizziness and Diplopia

Hashimoto’s encephalopathy (HE) is an uncommon neurological disorder characterized by subacute encephalopathy with elevated serum levels of thyroid autoantibodies. Due to the absence of specific tests and the diversity of neurological symptoms and signs, the diagnosis of HE is often delayed. We highlight the various manifestations of HE by reporting a patient who presented with atypical neurological signs such as dizziness and diplopia. The diagnosis was delayed until the patient progressed to cognitive impairment and generalized chorea.

Elevated plasma levels of specific antiplatelet glycoprotein autoantibodies in patients with primary Sjögren syndrome with thrombocytopenia.

Thrombocytopenia is one of the primary Sjögren's syndrome (pSS) hematological manifestations. The objective of this study was to evaluate the possible roles of antiplatelet glycoprotein autoantibodies in the pathogenesis of thrombocytopenia in primary Sjögren's syndrome (pSS). The level of plasma anti-glycoprotein Ib, IIIa and IIb/IIIa autoantibodies in 36 pSS patients without thrombocytopenia and 35 pSS patients with thrombocytopenia, 36 Idiopathic thrombocytopenic purpura (ITP) patients and 39 normal control were measured with enzyme-linked immunosorbent assay (ELISA). The level of anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies (A490) in the pSS with thrombocytopenia was significantly higher than that of pSS without thrombocytopenia (0.813 ± 0.161 vs 0.688 ± 0.133; 0.917 ± 0.094 vs 0.802 ± 0.070; 0.911 ± 0.125 vs 0.782 ± 0.109). Incidences of the anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies in the pSS with thrombocytopenia was significantly higher than that of pSS without thrombocytopenia (25.7% vs 0%; 65.7% vs 11.1%; 31.4% vs 0%). In patients with pSS, there was a lower platelet count in anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies positive patients ((25.67 ± 5.5) × 10^9/L vs (116.8 ± 84.52) × 10^9/L; 29.04 ± 11.33 × 10^9/L vs (152.0 ± 75.47) × 10^9/L; (31.55 ± 14.0) × 10^9/L vs (118.8 ± 85.24) × 10^9/L). Elevated plasma levels of anti-platelet glycoprotein autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS. Key Points • The level of anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies (A490) in the pSS with thrombocytopenia was increased. • Incidences of the anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies in the pSS with thrombocytopenia was increased. • In patients with pSS, there was a lower platelet count in anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies positive patients.

Abstract 16323: Functional Autoantibody Analysis in Post-Acute Sequela of COVID-19 Patients With and Without Pots: A Case Control Study

Introduction: Post-Acute Sequela of COVID-19 (PASC) occurs after recovery from the initial illness. Autonomic dysfunction (AD) may explain these findings. We have previously shown orthostatic intolerance (OI) on standard Italian protocol head-up tilt table in 23 of 24 prospectively studied subjects with PASC and no prior OI. Postural orthostatic tachycardia syndrome (POTS) was noted in 4 of the 23. POTS is associated with elevated levels of autoantibodies. There is a paucity of data evaluating autoantibody presence in subjects with PASC related POTS. Hypothesis: We hypothesized that individuals with PASC related POTS would demonstrate higher levels of certain autoantibodies than controls. Methods: We recruited healthy, COVID-19 PCR negative controls, all previously vaccinated for COVID, who were age and gender matched with the 4 previously identified PASC related POTS patients. Serum was tested for autoantibodies in both groups. Results: Mean ages for the PASC related POTS and control groups were 29 and 31 years, respectively. The PASC related POTS patients had higher levels of functional autoantibodies to several G-protein coupled receptors than controls. The median values for adrenergic A1, adrenergic B2, muscarinic M4, angiotensin 2 and endothelin receptors, comparing controls to PASC related POTS patients, were 10.4 vs 27.5, 14.9 vs 38.5, 7.8 vs 29.0, 12.2 vs 29.5 and 12.6 vs 31.7 Units/ml, respectively. The small size of the 2 groups precludes meaningful statistical testing, but the box plots in Figure 1 show consistent differences in the concentration of antibody receptors seen between the 2 groups. Conclusions: Functional autoantibodies to several G-protein coupled receptors were seen in higher amount in subjects with PASC related POTS compared to healthy controls. While this is a small, case-control study, it suggests a potential autoantibody mediated mechanism that may explain some of the AD seen in PASC patients with POTS.

Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.

Amyloid-like p53 as prognostic biomarker in serous ovarian cancer-a study of the OVCAD consortium.

TP53 is the most commonly mutated gene in cancer and has been shown to form amyloid-like aggregates, similar to key proteins in neurodegenerative diseases. Nonetheless, the clinical implications of p53 aggregation remain unclear. Here, we investigated the presence and clinical relevance of p53 aggregates in serous ovarian cancer (OC). Using the p53-Seprion-ELISA, p53 aggregates were detected in 46 out of 81 patients, with a detection rate of 84.3% in patients with missense mutations. High p53 aggregation was associated with prolonged progression-free survival. We found associations of overall survival with p53 aggregates, but they did not reach statistical significance. Interestingly, p53 aggregation was significantly associated with elevated levels of p53 autoantibodies and increased apoptosis, suggesting that high levels of p53 aggregates may trigger an immune response and/or exert a cytotoxic effect. To conclude, for the first time, we demonstrated that p53 aggregates are an independent prognostic marker in serous OC. P53-targeted therapies based on the amount of these aggregates may improve the patient's prognosis.

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.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are positively correlated with disease activity of bullous pemphigoid.

Bullous pemphigoid (BP) is a complex inflammatory process with elevated levels of autoantibodies, eosinophils, neutrophils, and various cytokines. Hematological inflammatory biomarkers can reflect inflammatory state in various diseases. Up to now, the correlations of hematological inflammatory biomarkers and disease activity of BP remain unknown. The purpose of this study was to clarify the associations between hematological inflammatory biomarkers and disease activity of BP. The levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR) and mean platelet volume (MPV) of 36 untreated BP patients and 45 age and gender matched healthy controls were detected by routine blood tests. The correlations between hematological inflammatory markers and clinical characteristics of BP were statistically analyzed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean levels of NLR, PLR, PNR and MPV in 36 untreated BP patients were 3.9, 157.9, 45.7 and 9.4fl, respectively. Increased NLR (p < 0.001), PLR (p < 0.01), and MPV (p < 0.001) but decreased PNR (p < 0.001) were observed in BP patients when compared with healthy controls. In BP patients, the levels of NLR were positively correlated to BPDAI Erosion/Blister Scores (p < 0.01); and the levels of NLR and PLR were both positively correlated to BPDAI without Damage Score (both p < 0.05) and BPDAI Total Score (both p < 0.05). No correlation was found in other statistical analyses between hematological inflammatory markers and clinical characteristics in BP patients involved in the present study. Therefore, NLR and PLR are positively correlated with disease activity of BP.

Survivors of Ebola virus disease exhibit elevated levels of autoantibodies

Abstract Survivors of Ebola virus disease (EVD) report a wide range of symptoms following recovery from acute viral infection, but underlying mechanisms are unclear. Many of these symptoms, collectively termed Post-Ebola Syndrome (PES), occur in the absence of detectable virus and resemble symptoms associated with autoimmune disease, such as arthralgia and myalgia, suggesting that EVD survivors may be experiencing a virus-induced autoimmune response. Studies in mice have shown that mice develop autoantibodies (autoAb) against HSP-60 and double stranded (ds) DNA that can bind to host tissues following Ebola virus (EBOV) infection. To determine if human EVD survivors also develop autoAb that may be associated with PES development, we profiled the humoral immune response of 354 survivors and 195 household contacts (HHC) from the 2014–2016 outbreak in Sierra Leone. Using Systems Serology, we measured the levels of antibodies against common autoantigens and found that EVD survivors had elevated levels of autoAb against dsDNA, HSP-60, IFNα, and citrullinated histone compared to HHC. As a subset of HHC were seropositive for EBOV glycoprotein (GP)-specific antibodies, separation of HHC into GP-seropositive and seronegative groups showed that the levels of autoAb in GP-seropositive HHC were elevated compared to GP-seronegative HHC, strongly suggesting that exposure/infection to EBOV tracks with presence of autoAb. As antibodies can activate innate immune cells via the antibody Fc domain, current studies are focused on analyzing the innate effector response mediated by these autoAb in EVD survivors and seropositive HHC. Together, our study highlights the potential role of autoAb in long-term sequelae associated with survival from EVD.

The role of immune disfunction in schizophrenia pathogenesis

IntroductionIn the last years there has been increasing evidence that inflammation and autoimmunity may play a role in the pathogenesis of schizophrenia.Although the brain has been considered an immune-privileged site, we understand now that infections and inflammation interfere with the blood-brain barrier, making the brain vulnerable to antibodies, cytokines and infectious agents.ObjectivesTo understand the role of immune disfunction in schizophrenia pathogenesis, as well as the potential role of immunotherapy in its treatment.MethodsWe performed a narrative review of the evidence, using the following terms and their combinations “schizophrenia”, “autoimmunity” and “monoclonal antibodies”.ResultsIt is widely known that prenatal, perinatal and childhood exposure to infections, nutritional deficits and other environmental insults, acting on a background of genetic vulnerability, may lead to schizophrenia. In such cases, we can observe potent and enduring inflammatory responses, such as cytokines dysregulations.State markers, including IL-1β, IL-6 and TGF-β have increased levels during exacerbation of symptoms and stabilized levels when antipsychotics are administrated. Trait markers, such as IL-12, IFN-γ and TNF-α have systematically increased levels in acutely and chronically ill patients, even during clinical stability.Moreover, patients with schizophrenia have been showing abnormalities of the blood-brain barrier, signs of central nervous system inflammation and elevated autoantibody levels and reactivity.Several autoimmune diseases are associated with schizophrenia, such as celiac disease, Graves’ disease and psoriasis. On the other hand, it is known since the 1950’s that schizophrenia has a negative association with rheumatoid arthritis.There are case reports of people with psychosis that were treated with immunosuppressive agents (for concurrent autoimmune diseases) that showed improvement in their psychotic symptoms.NSAIDs, immunomodulators and several monoclonal antibodies have been tested as potential treatments for schizophrenia. The results were conflicting but promising. It is suggested that not every patient with schizophrenia may benefit from these treatments. Ideally, treatment targeting the immune system should be provided in earlier phases of disease, such as in prodromal psychosis and first episode psychosis, because these are related to irreversible grey matter loss which causes cognitive decline.ConclusionsImmune dysregulation may have an important etiological role in schizophrenia.Hence, specific therapeutic approaches targeting the immune system may lead to new ways of treating and even preventing psychotic disorders.Further investigation is necessary in order to provide more information on how aberrant antibody and cytokine production interferes with neuronal function and how it is expressed at the clinical level.Disclosure of InterestNone Declared

Treatment of Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by elevated levels of transaminases, immunoglobulin G, and positive autoantibodies. The disease course is dynamic and presents heterogeneous disease manifestations at diagnosis. This review summarizes the issues regarding the treatment and monitoring of AIH in adult patients. Glucocorticoids and azathioprine are the first line of treatment. Alternative first-line treatments include budesonide or mycophenolate mofetil (MMF). Although no randomized controlled trials have been performed, MMF, cyclosporine, tacrolimus, 6-mercaptopurine, 6-thioguanine, allopurinol, sirolimus, everolimus, infliximab, or rituximab have been attempted in patients not responding to or intolerant to first-line treatments. Most patients require life-long special monitoring, with or without maintenance treatment.

Autoantibodies to PAX5, PTCH1, and GNA11 as Serological Biomarkers in the Detection of Hepatocellular Carcinoma in Hispanic Americans

Studies have demonstrated that autoantibodies to tumor-associated antigens (TAAs) may be used as efficient biomarkers with low-cost and highly sensitive characteristics. In this study, an enzyme-linked immunosorbent assay (ELISA) was conducted to analyze autoantibodies to paired box protein Pax-5 (PAX5), protein patched homolog 1 (PTCH1), and guanine nucleotide-binding protein subunit alpha-11 (GNA11) in sera from Hispanic Americans including hepatocellular carcinoma (HCC) patients, patients with liver cirrhosis (LC), patients with chronic hepatitis (CH), as well as normal controls. Meanwhile, 33 serial sera from eight HCC patients before and after diagnosis were used to explore the potential of these three autoantibodies as early biomarkers. In addition, an independent non-Hispanic cohort was used to evaluate the specificity of these three autoantibodies. In the Hispanic cohort, at the 95.0% specificity for healthy controls, 52.0%, 44.0%, and 44.0% of HCC patients showed significantly elevated levels of autoantibodies to PAX5, PTCH1, and GNA11, respectively. Among patients with LC, the frequencies for autoantibodies to PAX5, PTCH1, and GNA11 were 32.1%, 35.7%, and 25.0%, respectively. The area under the ROC curves (AUCs) of autoantibodies to PAX5, PTCH1, and GNA11 for identifying HCC from healthy controls were 0.908, 0.924, and 0.913, respectively. When these three autoantibodies were combined as a panel, the sensitivity could be improved to 68%. The prevalence of PAX5, PTCH1, and GNA11 autoantibodies has already occurred in 62.5%, 62.5%, or 75.0% of patients before clinical diagnosis, respectively. In the non-Hispanic cohort, autoantibodies to PTCH1 showed no significant difference; however, autoantibodies to PAX5, PTCH1, and GNA11 showed potential value as biomarkers for early detection of HCC in the Hispanic population and they may monitor the transition of patients with high-risk (LC, CH) to HCC. Using a panel of the three anti-TAA autoantibodies may enhance the detection of HCC.

Dysregulated Levels of Circulating Autoantibodies against Neuronal and Nervous System Autoantigens in COVID-19 Patients.

COVID-19 is a heterogenous disease resulting in long-term sequela in predisposed individuals. It is not uncommon that recovering patients endure non-respiratory ill-defined manifestations, including anosmia, and neurological and cognitive deficit persisting beyond recovery-a constellation of conditions that are grouped under the umbrella of long-term COVID-19 syndrome. Association between COVID-19 and autoimmune responses in predisposed individuals was shown in several studies. To investigate autoimmune responses against neuronal and CNS autoantigens in SARS-CoV-2-infected patients, we performed a cross-sectional study with 246 participants, including 169 COVID-19 patients and 77 controls. Levels of antibodies against the acetylcholine receptor, glutamate receptor, amyloid β peptide, alpha-synucleins, dopamine 1 receptor, dopamine 2 receptor, tau protein, GAD-65, N-methyl D-aspartate (NMDA) receptor, BDNF, cerebellar, ganglioside, myelin basic protein, myelin oligodendrocyte glycoprotein, S100-B, glial fibrillary acidic protein, and enteric nerve were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Circulating levels of autoantibodies were compared between healthy controls and COVID-19 patients and then classified by disease severity (mild [n = 74], severe [n = 65], and requiring supplemental oxygen [n = 32]). COVID-19 patients were found to have dysregulated autoantibody levels correlating with the disease severity, e.g., IgG to dopamine 1 receptor, NMDA receptors, brain-derived neurotrophic factor, and myelin oligodendrocyte glycoprotein. Elevated levels of IgA autoantibodies against amyloid β peptide, acetylcholine receptor, dopamine 2 receptor, myelin basic protein, and α-synuclein were detected in COVID-19 patients compared with healthy controls. Lower IgA autoantibody levels against NMDA receptors, and IgG autoantibodies against glutamic acid decarboxylase 65, amyloid β peptide, tau protein, enteric nerve, and S100-B were detected in COVID-19 patients versus healthy controls. Some of these antibodies have known clinical correlations with symptoms commonly reported in the long COVID-19 syndrome. Overall, our study shows a widespread dysregulation in the titer of various autoantibodies against neuronal and CNS-related autoantigens in convalescent COVID-19 patients. Further research is needed to provide insight into the association between these neuronal autoantibodies and the enigmatic neurological and psychological symptoms reported in COVID-19 patients.

The development of immunosorbents for the treatment of systemic lupus erythematosus via hemoperfusion.

Systemic lupus erythematosus (SLE) is an autoimmune disease (AID) that involves multiple organ systems and is characterized by elevated levels of autoantibodies (ANA) and immune complexes. The immunoadsorption technique uses an extracorporeal clearance process to remove pathogenic toxins from patients' blood and alleviate disease symptoms. An immunosorbent is a key component of the immunoadsorption system that determines therapeutic efficacy and safety. Immunosorbents are prepared by immobilizing antibodies, antigens, or ligands with specific physicochemical affinities on a supporting matrix. Immunosorbents and pathogenic toxins bind via affinity adsorption, which involves electrostatic interactions, hydrogen bonds, hydrophobic interactions, and van der Waals forces. Immunosorbents are classified on the basis of their interaction mechanism with toxins into three categories: non-selective, semi-selective, and highly selective. This review aimed to summarize the current status of various commercial immunosorbents that are used to treat SLE. Moreover, recent developments in immunosorbents have heightened the need for a brief discussion about specific ligands and a supporting matrix.