Nuclear Antigens Research Articles

Increased antinuclear (anti-Sm) antibodies in infertile patients with peritoneal endometriosis.

The aim of this study is to evaluate the intensity of five antibodies against extractable nuclear antigens (ENA: RNP, ScL-70, SS-B, SS-A, and Sm) in infertile patients with endometriosis. We investigated infertile women with minimal/mild endometriosis (n=43) and fertile women (n=46). The intensity of immunoreactions was also similar for anti-RNP and anti-SS-A antibodies. However, the intensity of immunoreactivity for anti-Sm antibodies was higher in the endometriosis group. Patients with minimal/mild endometriosis have higher levels of anti-Sm autoantibodies.

Autoantibodies Directed Against Interferon Alpha, Nuclear Antigens, Cardiolipin, and Beta 2 Glycoprotein 1 Are Not Induced By SARS-CoV-2 or Associated with Long COVID

Autoantibodies (AAbs) directed against interferon alpha (aIFNα), nuclear antigens (ANAs), cardiolipin (aCL), and beta 2 glycoprotein 1 (aβ2GP1), have been demonstrated to significantly correlate with the severity of acute COVID-19. However, whether SARS-CoV-2 infection induces these AAbs and whether they are associated with long COVID remains unclear. The potential induction of aIFNα, ANAs, aCL, and aβ2GP1 by SARS-CoV-2 was assessed by measuring these AAbs in 224 pre- and post-infection paired serum samples from the Johns Hopkins Hospital Emergency Department (JHHED). The relationship between these AAbs and long COVID was assessed using 60 serum samples from participants in the Outpatient SARS-CoV-2 Mild and Asymptomatic Infection Response and Transmission (OutSMART) study. We found no evidence that these AAbs were induced in the JHHED cohort and no significant difference in their prevalence between patients with (n=30) and without (n=30) long COVID in the OutSMART cohort. These findings do not support the hypotheses that SARS-CoV-2 induces these AAbs or that they are related to long COVID.

Diagnostic value of antibody immunoblotting detection in rheumatoid arthritis patients

Objective. To assess the diagnostic value of antinuclear antibody (ANA) profiling in rheumatoid arthritis by immunoblotting.Materials and methods. In total, 46 patients with rheumatoid arthritis (RA) with a mean age of 34.6 years (21.3–63.2) were observed. The disease duration was 11.2 years (3.7–19.8); the activity according to DAS 28 was 3.15 ± 1.36 (3.05–3.61) points. The RA diagnosis was based on generally accepted clinical guidelines. The control group included 28 patients with osteoarthritis. Laboratory examinations were conducted using a set of reagents to determine IgG antibodies to nuclear antigens by immunoblotting. Results. The RA patients showed an increased level of antibodies to the RNP/Sm antigen, with its frequency being significantly higher than in the control group (p = 0.007). The most specific testomes for diagnosing RA were anti-RNP/Sm (specificity 96%, sensitivity 25%) and antibodies to the recombinant antigen (sensitivity 25%, specificity 88.1%). The method of ROC analysis found that the value of anti-RNP/Sm = 0 is the point corresponding to the optimal ratio of sensitivity/specificity. This value corresponds to a sensitivity of 50% and a specificity of 73.8%.Conclusion. The studied laboratory tests, as a rule, showed high specificity, but rather low sensitivity. The most specific test for RA is anti-RNP/Sm. The conducted ROC analysis showed that the anti-RNP/Sm test has an average quality index for diagnosing RA.

Free Immunoglobulin Light Chains in Patients With Myocarditis: a New Biomarker of Inflammation and Heart Failure

To study the concentration of immunoglobulin free light chains (FLCs) in patients with myocarditis in comparison with non-inflammatory heart diseases, their relationship with inflammatory markers and the severity of chronic heart failure (CHF). This study included 77 patients (31 women, mean age 54.1±13.3 years): 41 patients with myocarditis verified by myocardial biopsy (n=18) or using a noninvasive diagnostic algorithm, 31 patients with noninflammatory CHF (comparison group), and 5 patients with monoclonal gammopathy identified during the study (4 of them were diagnosed with AL amyloidosis with heart damage). In the myocarditis group, CHF was diagnosed in 29 patients, mean stage IIA, functional class (FC) 2-3, with a mean left ventricular ejection fraction 43%. In the comparison group, patients had predominantly IIA stage, FC 2-3 CHF without systolic dysfunction. The blood concentration of kappa and lambda FLC types was measured with Cloneus S-FLC-K TIA Kit and Cloneus S-FLC-L TIA Kit. Concentrations were considered normal at FLC-kappa 4.84-14.20 mg/l, FLC-lambda 7.03-22.50 mg/l, and the FLC-kappa/lambda ratio 0.426-1.050. Increased FLC concentrations were found in 58% of patients with myocarditis and in 77% of patients in the comparison group. The FLC-lambda concentration was significantly higher in the comparison group; there were no significant differences between the groups in FLC-kappa and their ratio. The closest significant correlations in both groups and the entire cohort were noted between FLCs of either type and CHF, as well as the requirement for loop diuretics (correlation coefficients, 0.60-0.90), independent on the severity of systolic dysfunction. Myocarditis patients also showed correlations of FLCs with the titer of antibodies to cardiomyocyte nuclear antigens, levels of C-reactive protein, leukocytes, neutrophils, erythrocyte sedimentation rate, and the concentration of N-terminal fragment of brain natriuretic peptide. In a subgroup of 10 myocarditis patients who were treated with immunosuppressants, FLCs of both types were significantly lower than in the comparison group; only with the persistence of severe CHF was an increase in FLCs noted. An increased FLC concentration can be considered as an important pathogenesis component that reflects both the specific mechanisms of myocarditis and the severity of CHF. In the absence of a statistically significant increase in general inflammatory markers in the blood of myocarditis patients, the measurement of FLCs can be used as an additional diagnostic marker and predictor of the decompensated variant of the course of myocarditis. However, the diagnostic and prognostic significance of FLC concentration in patients without CHF requires a further study.

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Exposure to Gold Induces Autoantibodies against Nuclear Antigens in A.TL Mice.

To demonstrate causation or/and assess pathogenic mechanisms of environment-induced autoimmunity, various animal models that mimic the characteristics of the human autoimmune diseases need to be developed. Experimental studies in mice reveal the genetic factors that contribute to autoimmune diseases. Here, the immune response of two mouse strains congenic for non-H-2 genes, A.TL (H-2tl) and A.SW (H-2s), was evaluated after 15 weeks' exposure to gold aurothiomalate (AuTM). AuTM-treated A.TL mice showed anti-nuclear antibodies (ANA) with homogenous and/or fine speckled staining patterns and serum autoantibodies to ds-DNA, chromatin, histones, and ribonucleoproteins (RNP). Female A.TL mice showed a stronger immune response than males, as well as an increase of B cells in their spleen after 15 weeks of gold exposure. A.SW exposed for AuTM showed the induction of anti-nucleolar antibodies (ANoA) with a clumpy staining pattern, as well as an increase in splenic B and T cells. The serum autoantibodies levels in A.SW mice were limited compared to those of A.TL mice. Overall, A.TL presents a stronger immune response after gold exposure than A.SW. The immune response developed in A.TL presents similarities with the clinical manifestations in human autoimmune diseases. Thus, gold-exposed A.TL could constitute a potential experimental mouse model for the study of autoimmunity.

Induced tumor associated autoantibodies (iTAAs) by hapten plus drugs for targeting oncogenic nuclear antigens at sentinel lymph node of pancreatic cancer

Background: the abscopal is a hypothesis of effect on non-irradiated tumors after localized radiation therapy which associated with the products of tumor-associated gene as autoantibodies (aTAAs) in reaction to the tumor-associated antigens (TAAs). When TAAs interact with hapten within tumor after hapten plus chemotherapy drugs intratumoral injection to pancreatic cancer like tumor lysates vaccine, TAAs-hapten stimulates the immune system as a neu antigen and produces autologous tumor antibodies, it is called induced tumor-associated autoantibodies (iTAAs) which is lightly difference to aTAAs since epitope of antigen linked with hapten. Method: immunofluorescence (IF) was applied for detect the binding of the iTAAs in tumor cells at sentinel lymph node. Results: aTAAS naturally could not target and bind the TAAs in tumor since due to immune tolerance. The iTAAs can target and bind the TAAS, also the iTAAs targeted in the tumors of sentinel lymph node with complements C help, it was found Cmyc (P = 0.0017 at one week; P = 0.0001 at two weeks), p53 (P = 0.0373; 29.13 ± 6.91, and P = 0.0254), and Zeta (P = 0.1513, P = 0.0044) increased significantly in the tumor cells or perinuclear tumor cells in lymph node at one and two weeks after treatment. Conversely, IMP1 (P = 0.6154; P = 0.0138), Koc (P = 0.5684, P = 0.0103), Survivn (P = 0.1020; P = 0.0147) and Rala (P = 0.3226; P = 0.0249) increased significantly in the cell or perinuclear of tumor in lymph node at two weeks later following. Conclusions: it indicated all of iTAAs plays a function in the binding of original cellular tumor genes at sentinel lymph node while the aTAAs could not bind the cellular tumor genes at lymph node due to immune tolerance. We could make a hypothesis: TAAs inside the cancer cells’ nuclei can be targeted by the iTAAs which produced by hapten enhanced intratumoral chemotherapy. The iTAA may play a distinctive role in controlling tumor cell growth and resulting in an abscopal effect, which is one of hapten associated with TAA induced immune response.

Mechanisms underlying sex differences in autoimmunity.

Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune diseases occur more often in women than men, with rheumatic autoimmune diseases being among those most highly expressed in women. Several key factors, identified mainly in animal models and cell culture experiments, are important in increasing autoimmune disease in females. These include sex hormones, immune genes including those found on the X chromosome, sex-specific epigenetic effects on genes by estrogen and the environment, and regulation of genes and messenger RNA by microRNAs found in extracellular vesicles. Evidence is also emerging that viruses as well as drugs or toxins that damage mitochondria may contribute to increased levels of autoantibodies against nuclear and mitochondrial antigens, which are common in many autoimmune diseases. The purpose of this Review is to summarize our current understanding of mechanisms that may determine sex differences in autoimmune disease.

Pathogenic role of anti-nuclear autoantibodies in systemic sclerosis: Insights from other rheumatic diseases.

Systemic sclerosis (SSc) is a severe autoimmune disease characterized by vasculopathy, fibrosis, and dysregulated immunity, with hallmark autoantibodies targeting nuclear antigens such as centromere protein (ACA) and topoisomerase I (ATA). These autoantibodies are highly prevalent and disease-specific, rarely coexisting, thus serving as crucial biomarkers for SSc diagnosis. Despite their diagnostic value, their roles in SSc pathogenesis remain unclear. This review summarizes current literature on ACA and ATA in SSc, comparing them to autoantibodies in other rheumatic diseases to elucidate their potential pathogenic roles. Similarities are drawn with anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis, particularly regarding disease specificity and minimal pathogenic impact of antigen binding. In addition, differences between ANA and ACPA in therapeutic responses and Fab glycosylation patterns are reviewed. While ACA and ATA are valuable for disease stratification and monitoring activity, understanding their origins and the associated B cell responses is critical for advancing therapeutic strategies for SSc.

Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. SLE pathogenesis involves genetic, environmental, and hormonal factors. The disease course includes flares and remission and involves various organs. Recent therapeutic progresses, including biologics, have improved management and prognosis, though the long-term impact of novel therapies remains to be determined. Biologics in SLE: Rituximab, the earliest B-cell-oriented biologic, binds CD20 and depletes CD20+ B cells, leading to remission in some SLE patients. Belimumab is a B-cell-activating factor (BAFF) inhibitor with a recent additional indication for lupus nephritis. The CALIBRATE and BLISS-BELIEVE studies investigated combinations of these drugs with conventional therapies, showing varied efficacy. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. The latest trials highlight their efficacy and safety. Anifrolumab, targeting type-I interferon receptors, was evaluated in the TULIP 1/2 trials. The ongoing TULIP LTE trial supports the long-term safety and efficacy of anifrolumab. Additionally, the IRIS Phase III trial is exploring anifrolumab for lupus nephritis, showing favorable renal responses. Tocilizumab and secukinumab are being assessed for SLE, with mixed outcomes. Several biologics targeting the C5 complement protein, together with immunomodulators and immunotherapeutics, are also under investigation for potential benefits in SLE. Biologics in SLE target specific immune components, aiming to improve disease control and reduce the side effects of conventional therapy. However, trial outcomes vary due to factors like inclusion criteria and trial design. Biotechnology progress enables targeted biologic therapies for SLE, reducing disease activity and improving patients' quality of life.

Abstract P180: Female mice with systemic lupus erythematosus produce antibodies to mitochondrial antigens and have impaired renal mitochondrial function

Patients with autoimmune disorders like systemic lupus erythematosus (SLE) are at significant risk for renal and cardiovascular mortality. The pathology of SLE is driven by a loss of immune tolerance with the subsequent production of autoantibodies (IgG), and our laboratory previously demonstrated a mechanistic role for autoantibodies in autoimmune mediated hypertension. While anti-double stranded DNA (dsDNA) antibodies are pathognomonic for SLE, a breadth of autoantibodies may contribute to disease pathology. The goal of this study is to identify autoantibodies that may contribute to the renal and cardiovascular consequences associated with SLE. To accomplish this goal, an antigen array was performed (University of Texas Southwestern Genomics &amp; Microarray Core Facility) using plasma samples collected from an established experimental mouse model of SLE (30 week old female NZBWF1, n=8) and healthy controls (30 week old female NZWLacJ, n=7). As anticipated, autoantibodies raised to nuclear antigens were prominently represented in the array and were significantly increased relative to control mice. This includes antibodies to dsDNA, ssRNA, chromatin, and histones (total) (p&lt;0.02). In addition, SLE mice produce antibodies to mitochondrial antigens including cardiolipin and cytochrome C (p&lt;0.02 vs control mice), critical components of the inner mitochondrial membrane and respiratory chain, respectively. In a separate study, renal mitochondrial function was tested using high resolution respirometry (Oroboros Instruments) in whole kidney homogenates from 30 week old female SLE (n=6) and control mice (n=5). Results show that coupled respiration, an estimation of oxidative phosphorylation, is significantly impaired at Complex I in kidneys from SLE mice compared to healthy controls (62±9 vs. 90±7 pmol/s/mg tissue, p&lt;0.05). Uncoupled respiration, an estimation of maximal electron transport, is also reduced in the kidneys of female SLE mice compared to controls (157±23 vs. 212±14 pmol/s/mg tissue, p=0.07). These data provide insight for new mechanistic pathways to pursue in understanding the underlying mechanisms promoting cardiovascular risk factors like hypertension during SLE.

An Uncommon Case Report of Hypothyroidism, Type 1 Diabetes Mellitus, and Systemic Lupus Erythematosus with an Immunosuppressive Consequence: A Case Report

An autoimmune condition known as Systemic Lupus Erythematosus (SLE) affects several systems and manifests itself in a variety of ways. It is far more common among young women who are fertile. It has been demonstrated that a mix of environmental and genetic variables may trigger immunological responses, triggering T and B cells, and leading the B cells to overproduce pathogenic autoantibodies and dysregulate cytokines, which ultimately result in harm to many organs and tissues. One feature of SLE is the presence of antibodies against cytoplasmic and nuclear antigens. An autoimmune illness is also type 1 diabetes. β-cell antibodies (Ab) and other antibodies that cause the autoimmune death of the pancreatic β-cells, which make insulin, are part of the multifactorial pathophysiology of type 1 diabetes mellitus (T1DM). Immunosuppression is the therapy for systemic lupus erythematosus (SLE), and diabetes itself compromises immunity, making infections more opportunistic. We came across an unusual instance of a patient with SLE, T1DM, hypothyroidism on immunosuppression who subsequently acquired pulmonary TB. Key phrase: Autoimmune diseases such as type 1 diabetes mellitus (T1DM) and Systemic Lupus Erythematosus (SLE).

Evaluating Autoimmune Markers in Relation to Gastrointestinal Measures in Patients With Symptoms of Gastroparesis.

Patients with symptoms (Sx) of gastroparesis (Gp) may have signs of autoimmune disease. We hypothesized that serum autoantibodies in Gp Sx patients are associated with follow-up at 48 weeks (about 11mo) and later autoimmune questionnaires (AQ). One hundred eleven patients: 24 male, 87 female, mean age 43 years, with Gp Sx: 27 diabetic (DM), 78 idiopathic (ID), 6 postsurgical (PS) were studied at baseline, 48 weeks (about 11mo) and long term. Serum western blot (WB) was performed by an enzyme linked immunosorbent assay for qualitative evaluation of serum antibodies to various specific nuclear antigens. A blotting score (GIBS) was used to compare global immunologic reactions. At long-term follow-up (>5y), 38 AQ-responding patients (34 with baseline WB data) were compared with WB by AQ responses. A total of 69/111 (62%) had gastric emptying delay. Correlations exist between WB autoantibodies and clinical follow-up at 48 weeks (about 11mo). 94/96 (97.9%) were WB positive and 62/96 patients had 48-week data. From 5 years follow-up of 38 patients, AQ Sx responses were recurring abdominal pain (89%), lack of energy (87%), exhaustion (74%), and constipation (68%). From AQ and WB data (34 patients), Anti-SSA was higher in those indicating dry mouth and mouth and nose sores and SM was higher in dysphagia (P=0.01 for both). Conclusions In patients with gastroparesis symptoms baseline western blot has significant associations with a number of clinical findings and autoimmune disorders symptoms. These associations suggest possible undiagnosed autoimmune disorders. Further work with Western blotting and other autoimmune measures in patients with gastroparesis symptoms is needed.

A study of the correlation between phospholipase A2 enzyme activity and anti-complement antibodies in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs or organ systems. SLE and one of its most common complications, lupus nephritis (LN), are characterized by chronic inflammation due to the secretion of pro-inflammatory molecules and a tissue deposition of immune complexes formed by autoantibodies and their target antigens, such as double-stranded DNA, other nuclear antigens, and complement proteins. Increased activity of phospholipase A2 enzymes (PLA2) like calcium-independent PLA2 (iPLA2), secretory PLA2 (sPLA2), and cellular PLA2 (cPLA2) has a crucial role in the maintenance of the inflammatory process during the course of SLE. This study aimed to evaluate PLA2 activity and identify the dominant type of PLA2 enzymes in a cohort of Bulgarian patients with SLE and LN. Additionally, we investigated whether the increased PLA2 activity was correlated with the presence of autoantibodies specific to the complement proteins C3 and factor H.

Macaque liver substrate for evaluating dense fine speckled-like patterns on HEp2010 cells

Antinuclear antibody (ANA) detection by indirect immunofluorescence (IIF) is instrumental in the evaluation of systemic autoimmune diseases (SADs). The dense fine speckled (DFS) ANA staining predominantly associates with anti-DFS70, an autoantibody that is thought to exclude the presence of SAD. However, the DFS pattern may mask the presence of other ANA patterns that may be clinically relevant. Our laboratory uses the HEp2010 substrate which contains both HEp2 and liver substates. The aim of this study was to determine whether negative liver nucleus immunofluorescence could exclude the presence of antibodies to extractable nuclear antigens (ENA) in sera with DFS-like patterns. One hundred consecutive sera samples suspicious for DFS pattern, along with 15 sera of control patterns (positive metaphase bars) were included in the study. Each sample was examined separately on HEp2010 (Euroimmun) and liver by two independent readers. Anti-DFS70 was assessed by line and chemiluminescent immunoassays. DFS-like sera were more likely to be liver nucleus-negative compared with control sera. Of the liver-negative sera, 61/64 (95.3%) were deemed anti-ENA negative. Using the liver substrate in the evaluation of anti-ENA had a sensitivity of 90.0% and a negative predictive value of 95.4%. In our cohort, concurrent evaluation of sera with the liver substrate helped rule out the presence of other anti-ENA. This technique may be a safeguard for DFS-like ANA patterns that may mask underlying anti-ENA on IIF.

Autoimmune diseases, autoantibody status and silicosis in a cohort of 1238 workers from the artificial stone benchtop industry

ObjectivesAutoimmune disorders are multifactorial but occupational exposures have long been implicated, including respirable crystalline silica (RCS). A modern epidemic of silicosis is emerging internationally, associated with dry processing of engineered...

Up-Regulation of microRNA-34a in Women with Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease with multiple contributing factors. It is characterized by the immune system's inability to tolerate autoantigens such as nuclear antigens. The objective of this study is to evaluate the expression of microRNA-34a in relation to the incidence and occurrence of SLE in Iraqi women using quantitative real-time PCR and to determine its potential relationship with various demographic and laboratory parameters and disease activity. This investigation enrolled 100 healthy controls with a mean age of 31.68 years and 100 SLE patients, all of whom were women with a mean age of 32.85 years and a disease duration of 9.00 (6.75) years. The mean of the Systemic Lupus Erythematosus disease activity index (SLEDAI-2k) score was 10.860±3.275. Erythrocyte sedimentation rate, C-reactive protein, urea, and creatinine were significantly higher (50.00 vs. 10.00 mm/h, 16.70 vs. 0.650 mg/dl, 58.00 vs. 33.00 mg/l, and 1.550 vs. 0.700 mg/l, respectively), while hemoglobin, white blood cells, and Complement 3 and Complement 4 were significantly lower (8.40 vs. 13.00 g/dl, 3.500 vs. 6.800 x 109 /L, 74.00 vs. 130.00 mg/dl, and 10.00 vs. 13.50 mg/dl, respectively) in patients with SLE compared with controls (P≤ 0.001). The analysis of anti-nuclear antibodies (ANA) in patients showed that 89% have ANA and 95% have anti-double-stranded DNA (anti-dsDNA). Also, the findings revealed a significant increase in microRNA-34a expression with fold change (5.19 ±0.48) when compared to the fold change mean in controls (1.00 ±0.00). There is no evidence for any correlation between microRNA-34a fold change and any laboratory or demographic examination of the illness in the present study except for age and BMI. In addition, receiver operating characteristic (ROC) analysis was performed on SLE patients to establish the diagnostic accuracy of microRNA-34a in differentiating SLE patients from controls. The specificity and sensitivity of microRNA-34a were 98% and 100%, respectively. The area under the curve (AUC) was 0.990, and the cutoff point was 1.050. This indicates that the identified microRNA-34a may represent strong biomarkers for SLE disorders.

Epstein-Barr Viruses: Their Immune Evasion Strategies and Implications for Autoimmune Diseases.

Epstein-Barr virus (EBV), a member of the γ-herpesvirus family, is one of the most prevalent and persistent human viruses, infecting up to 90% of the adult population globally. EBV's life cycle includes primary infection, latency, and lytic reactivation, with the virus primarily infecting B cells and epithelial cells. This virus has evolved sophisticated strategies to evade both innate and adaptive immune responses, thereby maintaining a lifelong presence within the host. This persistence is facilitated by the expression of latent genes such as EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), which play crucial roles in viral latency and oncogenesis. In addition to their well-known roles in several types of cancer, including nasopharyngeal carcinoma and B-cell lymphomas, recent studies have identified the pathogenic roles of EBV in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This review highlights the intricate interactions between EBV and the host immune system, underscoring the need for further research to develop effective therapeutic and preventive strategies against EBV-associated diseases.

B cells secrete functional antigen-specific IgG antibodies on extracellular vesicles

B cells and the antibodies they produce are critical in host defense against pathogens and contribute to various immune-mediated diseases. B cells responding to activating signals in vitro release extracellular vesicles (EV) that carry surface antibodies, yet B cell production of EVs that express antibodies and their function in vivo is incompletely understood. Using transgenic mice expressing the Cre recombinase in B cells switching to IgG1 to induce expression of fusion proteins between emerald green fluorescent protein (emGFP) and the EV tetraspanin CD63 as a model, we identify emGFP expression in B cells responding to foreign antigen in vivo and characterize the emGFP+ EVs they release. Our data suggests that emGFP+ germinal center B cells undergoing immunoglobulin class switching to express IgG and their progeny memory B cells and plasma cells, also emGFP+, are sources of circulating antigen-specific IgG+ EVs. Furthermore, using a mouse model of influenza virus infection, we find that IgG+ EVs specific for the influenza hemagglutinin antigen protect against virus infection. In addition, crossing the B cell Cre driver EV reporter mice onto the Nba2 lupus-prone strain revealed increased circulating emGFP+ EVs that expressed surface IgG against nuclear antigens linked to autoimmunity. These data identify EVs loaded with antibodies as a novel route for antibody secretion in B cells that contribute to adaptive immune responses, with important implications for different functions of IgG+ EVs in infection and autoimmunity.

Genetic prion disease – fatal familial insomnia (clinical case)

Background. Fatal familial insomnia is a rare genetically determined neurodegenerative disorder from the group of prion diseases. Its main cause is the autosomal dominant D178N mutation of the PRNP gene, which leads to the synthesis of the pathological prion protein PrP.The aim. Using the example of a clinical case to describe an example of the early onset of fatal familial insomnia in a teenager, a clinical example of its management.Materials and methods. Female patient V., 16 years old, of hyposthenic constitution, undernourished, with negative family history (multiple sclerosis in her paternal grandmother) for the first time consulted a neurologist in Tver for the complaints of superficial sleep, shortened to 4–5 hours, unspecific pain all over the body, periodic numbness in the upper limbs. Six months later, retardation of speech and movements, changes in gait, and intentional tremor occurred; sleep was shortened to 2 hours. In the future, the teenager lost the ability to independently maintain the vertical body position, the ability to walk without assistance, speech was reduced to syllable answers to questions. In order to verify the diagnosis and to carry out differential diagnosis with other neurodegenerative diseases, the girl underwent auxiliary research methods: detection of antibodies to nuclear antigens, magnetic resonance imaging, computer electroencephalography, polyexomal genome sequencing.Results. Based on the anamnesis, complaints, clinical picture and results of genetic research the final diagnosis of fatal familial insomnia was made. Due to the lack of etiological and pathogenetic therapy, the patient was subsequently provided with palliative medical care. The fatal outcome occurred 19 months after the onset of the disease.Conclusions. The presented clinical case reflects the complexity of managing patients with rare genetic diseases, confirms the need for mandatory polyexomal genome sequencing in order to verify the diagnosis, which allows timely palliative care