Autoimmune Process Research Articles

Autoimmune Dysphagia Related to Rheumatologic Disorders: A Focused Review on Diagnosis and Treatment.

Autoimmune dysphagia is defined as dysphagia caused by autoimmune processes affecting various components of the swallowing processsuch as muscle, neuromuscular junction, nerves, roots, brainstem, or cortex. These autoimmune causes can be classified into gastroenterological, dermatological, rheumatologic, and neurologic. Rheumatological disorders, such as scleroderma, Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, Behcet's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, or granulomatosis with polyangiitis, have been associated with dysphagia. Autoimmune dysphagia in the context of rheumatological disorders is particularly significant because it can occur as a sole manifestation or as part of a symptom complex associated with the underlying disorder and often responds to immunosuppressive therapies. However, diagnosing autoimmune dysphagia can be challenging as it requires the exclusion of structural and primary motility disorders through procedures such as endoscopy and manometry. Early diagnosis is important to improve the quality of life and prevent significant mortality and morbidity. Management focuses on treating the underlying disease activity, and a multidisciplinary approach involving various medical specialties may be necessary to achieve success. This article aims to review the autoimmune rheumatological conditions that can lead to dysphagia and discuss the associated pathophysiological mechanisms. We also outline the clinical clues and laboratory testing methods that facilitate early diagnosis, with the goal of improving patient outcomes through timely intervention and appropriate management.

Diagnostic markers of yersiniosis in patients with inflammatory bowel diseases

Relevance. This study is related to the study of the etiology, pathogenesis and clinic of inflammatory bowel diseases (IBD). In a number of patients with IBD who are refractory to anti-inflammatory/immunosuppressive therapy, there are signs of current or transferred yersiniosis infection, not diagnosed by routine methods.Aim. According to the scientific literature and the results of our own research, to identify the presence and assess the nature of the influence of yersinia on the occurrence and development of IBD.Materials Methods. In our study, we conducted a bacteriological examination of feces by polymerase chain reaction (PCR) in patients with a diagnosis of IBD (UC and CD) in the acute phase (MMDAI ≥ 4 points for UC and Best index ≥ 150 points for CD), as well as immunological diagnostics using enzyme immunoassay (IFA) in the version of line-blotting (IB). Using the results obtained, clinical and instrumental semiotics were evaluated in subgroups of individuals suffering from IBD with confirmed yersiniosis ("IBD+ IER+") and without it ("IBC+ IER–"). We also assessed the role of intestinal infection by determining the effectiveness of initial antibacterial therapy in the treatment of exacerbation of IBD.Results. A significant part (in the case of our sample – 45%) of patients with IBD, when examined by high-tech methods, demonstrate the presence of markers of a transferred or current yersiniosis infection. Its role in the initiation and development of autoimmune intestinal inflammatory process requires further clarification.Conclusions. In 45% of patients with IBD, high-precision examination reveals markers of transferred or current yersiniosis infection. Routine clinical methods for the diagnosis of yersiniosis have low sensitivity and do not allow us to convincingly assess the role of this bacterial agent as a trigger factor for the onset or recurrence of IBD. There is a tendency for greater manifestation in the debut of IBD in patients with markers of systemic yersiniosis. The fact of improvement against the background of empirical antibacterial therapy in 24% of patients with IBD, achievement of early clinical remission in 57% of patients receiving antibiotic therapy, indicates a significant role of bacterial enterocolopathogens in the genesis of chronic intestinal inflammation in a number of patients.

COVID-19 vaccine and hepatitis: A mini review

Abstract An efficient vaccine is urgently required due to the high death rate and quick spread of the COVID-19 pandemic. Several reports on the side effects of the vaccine have focused on the negative effects of the COVID-19 inoculation. Clinical hepatology is quite concerned about the liver issue that manifests after receiving the COVID-19 vaccination. The COVID-19 vaccination may result in a variety of clinical problems, including hepatitis. Regarding the underlying pathogenesis, the autoimmune pathological process is usually mentioned. Immunopathological processes are likely to be implicated in the COVID-19 vaccine-related hepatitis, despite the fact that the exact cause is yet unknown.

Experiences in implementing immunopsychiatry in real life

Immunological mechanisms, both alone and in combination, are associated with a broad range of psychiatric disorders encompassing autoimmune, autoinflammatory disorders but also genetic, metabolic, or other immunological disorders. Early treatment improves the outcome for autoimmune disorders, but early diagnosis is more difficult when isolated psychiatric symptoms are manifestations of autoimmunity. Treatment of these cases must encompass integrated models of disease, as both systemic autoimmunity and psychological processes influence mental health. Several challenges need to be overcome to efficiently merge psychiatric and somatic disease paradigms and medical care ranging from language and conceptual barriers to organizational barriers. Since 2015, the Immunopsychiatry team at Uppsala University has developed a collaborative multidisciplinary approach to improve and integrate care for patients with moderate to severe psychiatric disorders. Based on this experience, we have outlined the obstacles to be overcome in taking steps forward to achieve the long-term goal of understanding and early detection and identification of treatable immunological conditions within the psychiatric patient population; the described framework of evaluations and work-flow may serve as a model for other centers.

Autoimmune nodo-paranodopathies 10 years later: Clinical features, pathophysiology and treatment.

Autoimmune neuropathies are classified, on the basis of pathophysiology, as demyelinating or axonal. The term nodo-paranodopathy, introduced in 2013 to better categorize the neuropathies with antiganglioside antibodies and later expanded to include neuropathies with antibodies to nodal and paranodal axoglial complexes, characterizes disorders in which the nodal region is critical in the pathogenesis. These neuropathies, although presenting electrophysiologic demyelinating features do not show pathologic evidence of segmental demyelination, or, although being classified as axonal, can show reversible nerve conduction failure and rapid recovery contrary with the communal concept of an axonal neuropathy. In this personal view is reported, with a splitting approach, an update on autoimmune nodo-paranodopathies, classified according to the domains of peripheral nerve fiber, the target antigens and the antibody class and subclass involved. The clinical features, the electrophysiologic findings, the results of the immunopathological and ultrastructural studies, the pathophysiology and treatment are also described. The nodo-paranodopathy category integrates the clinical classification of autoimmune neuropathies and expands the traditional dichotomous demyelinating and axonal classification. It helps to a better systematization pointing to the domain and target antigens of the autoimmune process, it resolves conflicting pathologic and electrophysiologic findings, reconciles the contradiction that axonal neuropathies may be rapidly reversible, avoids taxonomical confusion and possible misdiagnoses. Finally this categorization, through the identification of the specific antibody and its prevalent class and subclass, clarifies the pathophysiological mechanisms and addresses to a more targeted therapeutic approach.

Alemtuzumab-induced Graves' disease

Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves' disease (GD) develops most often, followed by autoimmune thyroiditis.We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.

The features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves’ disease in dynamics after radioactive iodine therapy

BACKGROUND: The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves’ disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease.AIM: To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves’ disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease.MATERIALS AND METHODS: A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves’ disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies.RESULTS: The study included 36 women with recurrent Graves’ disease, middle age 46.34±14.32 years. In patients with Graves’ disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves’ disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg.CONCLUSION: A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.

Diagnostic Challenge of Adult-onset Type 1 Diabetes Mellitus in a Remote Hospital

Type 1 Diabetes Mellitus (T1DM) is a chronic endocrinological disease due to an autoimmune process. The prevalence of T1DM is 9.5% worldwide, with the incidence of 15 out of 100,000 people, ranging from childhood to 40 years of age. Autoimmunity-related late-onset Diabetes Mellitus (DM) patients could be diagnosed as classic T1DM or latent autoimmune diabetes in adults (LADA). A 30-year-old male patient with unremarkable previous medical history was admitted to the emergency room with dyspnea for the last three days that was worsened six-hour before admission. Physical examinations showed a body Mass Index (BMI) of 18.75 kg/m2, irregular pulse, and Kussmaul breathing. The patient was diagnosed with diabetic ketoacidosis (DKA) on May 23, 2019. He was discharged with subcutaneous insulin pen injections. Two years later, he was readmitted with DKA due to discontinuing his treatment. He stated that the reason for stopping the insulin was because he was tired of injecting it. The patient was hospitalized and was discharged with oral antidiabetic agents to cope with his injection tiredness issue. One week later, the patient complained of dyspnea and was diagnosed with recurrent DKA. He was hospitalized and prescribed subcutaneous insulin. In this kind of situation, a diagnosis of LADA for patients presenting with DKA without prior history of DM in early adulthood needs to be considered. In contrast to the classic T1DM, the need for insulin occurs late in LADA. Affordable and widely available ancillary examinations are needed, including in remote hospitals. Finally, motivational support for patients is as important as the pharmacological treatment since lifelong insulin injections are needed.

The Effect of COVID-19 Severity, Associated Serum Autoantibodies and Time Interval after the Disease on the Outcomes of Fresh Oocyte ART Cycles in Non-Vaccinated Patients

It is assumed that SARS-CoV-2- and COVID-19-associated autoimmune processes may affect the outcomes of assisted reproductive technology (ART) cycles. This observational prospective study included 240 infertile patients: 105 patients had no history of COVID-19 (group 1) and 135 patients had experienced COVID-19 (group 2) in a mild (n = 85) or moderate (n = 50) form less than 12 months prior to oocyte retrieval. Using ELISAs, the profiles of their serum autoantibodies were determined, including antiphospholipid antibodies and antibodies to nuclear and thyroid antigens. The parameters of oogenesis and embryogenesis, as well as the pregnancy and childbirth rates, did not differ between groups 1 and 2, and also between the subgroups with different severities of COVID-19. However, when oocyte retrieval was performed less than 180 days after COVID-19, a higher proportion of poor-quality blastocysts was obtained (p = 0.006). A high risk of early miscarriage was found in the patients with moderate COVID-19. In group 2, IgG antibodies to annexin V, phosphatidylethanolamine (PE), and TSHr were detected more often than in group 1 (p = 0.035; p = 0.028; and p = 0.033, respectively), and a weak inverse correlation was revealed between anti-PE IgG and the number of oocytes and zygotes obtained. The results of the study suggest a possible adverse effect of COVID-19 and its associated autoantibodies on the outcomes of fresh oocyte ART cycles and early pregnancy, which depends on the severity of COVID-19 and the time interval after the disease.

Human peripheral blood age-associated (CD11c+Tbet+) B cells: No association with age.

Human peripheral blood age-associated (CD11c+Tbet+) B cells: No association with age.

Sweet’s Syndrome: A Rare Case Report

Sweet’s Syndrome, also known as acute febrile neutrophilic dermatosis is a rare disease of unknown etiology, but has been associated with autoimmune processes, malignancies, infections, GI disorders and drug reactions. It is more prevalent in women than men, except in case of malignancy associated origin. Clinical features of this disorder include acute onset of painful plaques on skin, neutrophilic leukocytosis, fever, dermal infiltrations by neutrophils. Usually, sweet’s syndrome is presented in three main clinical settings which includes: the classical (idiopathic), malignancy-associated, and drug induced. Classical Sweet’s Syndrome (CSS) is usually seen in women between the age of 30 to 50 years. It is frequently preceded by an upper respiratory illness and could be linked to pregnancy, inflammatory bowel disease, and both. Recurrence of the dermatosis is usually seen in one third of the patients experiencing classical sweet’s syndrome. Malignancy associated Sweet’s Syndrome (MASS) is usually present in patients with confirmed cancer and manifested as a paraneoplastic syndrome. Also occurs in those whose solid tumor or hematologic dyscrasia associated with sweet’s syndrome was previously undetected. Drug induced Sweet’s Syndrome (DISS) occurs in patients being treated with granulocyte-colony stimulating factor. Various other drugs including antibiotics like Minocycline, Trimethoprim Sulfamethoxazole, nitrofurantoin, antiepileptics like Carbamazepine, Diazepam, NSAIDS, Diuretics and Retinoids can also cause DISS. Diagnosis of sweet syndrome is usually done by two major criteria (histopathology and acute cutaneous lesion), and four minor criteria’s (infection, malignancy, medications, fever, and extra cutaneous manifestations like leukocytosis and corticosteroid response. Systemic corticosteroids are the golden standard of treatment for Sweet’s Syndrome. Systemic corticosteroids (0.5mg to 1mg/kg/day) for 4-6 weeks improves the systemic symptoms and reduce the skin lesions. For treating localized lesions, topical application of high potency corticosteroids or intralesional corticosteroids are effective. Other first line agents including potassium iodide and colchicine are also used. Second line agents include Indomethacin, Cyclosporine, Dapsone and Clofazimine. Keywords: Sweet’s Syndrome, Corticosteroids, Malignancy, Leukocytosis

A current and future perspective on T cell receptor repertoire profiling.

T cell receptors (TCR) play a vital role in the immune system's ability to recognize and respond to foreign antigens, relying on the highly polymorphic rearrangement of TCR genes. The recognition of autologous peptides by adaptive immunity may lead to the development and progression of autoimmune diseases. Understanding the specific TCR involved in this process can provide insights into the autoimmune process. RNA-seq (RNA sequencing) is a valuable tool for studying TCR repertoires by providing a comprehensive and quantitative analysis of the RNA transcripts. With the development of RNA technology, transcriptomic data must provide valuable information to model and predict TCR and antigen interaction and, more importantly, identify or predict neoantigens. This review provides an overview of the application and development of bulk RNA-seq and single-cell (SC) RNA-seq to examine the TCR repertoires. Furthermore, discussed here are bioinformatic tools that can be applied to study the structural biology of peptide/TCR/MHC (major histocompatibility complex) and predict antigenic epitopes using advanced artificial intelligence tools.

OSTEOLYSIS OF THE MANDIBLE AND PERIODONTITIS ASSOCIATED WITH RHEUMATOID ARTHRITIS AND METHOTREXATE

The citrullination process is exaggerated in rheumatoid arthritis, leading to abnormal accumulation of citrulline. Antibodies are released, triggering an autoimmune inflammatory process. Methotrexate, an antimetabolite and antifolate drug, used in arthritis, leads to myelosuppression favoring the appearance of opportunistic infections. Methotrexate therapy has side effects, which include oral manifestations. This report aimed to describe a case of periodontal disease with osteolysis of the mandible associated with rheumatoid arthritis and methotrexate therapy. A 38-year-old female presented a history of tooth mobility. Radiographic examination showed horizontal bone loss exceeding the middle third of the roots, in addition to bone rarefaction throughout the body of the mandible. Fine needle aspiration and an excisional biopsy with curettage of one of the lesions were performed, which yielded an inconclusive report. In the imaging follow-up, bone neoformation was observed in the biopsy region. The citrullination process is exaggerated in rheumatoid arthritis, leading to abnormal accumulation of citrulline. Antibodies are released, triggering an autoimmune inflammatory process. Methotrexate, an antimetabolite and antifolate drug, used in arthritis, leads to myelosuppression favoring the appearance of opportunistic infections. Methotrexate therapy has side effects, which include oral manifestations. This report aimed to describe a case of periodontal disease with osteolysis of the mandible associated with rheumatoid arthritis and methotrexate therapy. A 38-year-old female presented a history of tooth mobility. Radiographic examination showed horizontal bone loss exceeding the middle third of the roots, in addition to bone rarefaction throughout the body of the mandible. Fine needle aspiration and an excisional biopsy with curettage of one of the lesions were performed, which yielded an inconclusive report. In the imaging follow-up, bone neoformation was observed in the biopsy region.

Environmental factors in autoimmune bullous diseases with a focus on seasonality: new insights.

Autoimmune bullous diseases are a heterogeneous group of rare conditions clinically characterized by the presence of blisters and/or erosions on the skin and the mucous membranes. Practically, they can be divided into two large groups: the pemphigoid group and the pemphigus group, depending on the depth of the autoimmune process on the skin. A family history of autoimmune diseases can often be found, demonstrating that genetic predisposition is crucial for their development. Moreover, numerous environmental risk factors, such as solar radiation, drugs, and infections, are known. This study aimed to evaluate how seasonality can affect the trend of bullous pemphigoid and pemphigus vulgaris, especially considering the number of hospitalizations recorded over the course of individual months. The total number of hospitalizations in the twelve months of the year was evaluated. Moreover, blood chemistry assay and, for some patients, enzyme-linked immunosorbent assay were executed to evaluate antibodies. Regarding the severity of the disease, the bullous pemphigoid area index and the pemphigus disease area index score systems were used. Results showed a complex interplay between environmental factors such as seasons and autoimmune conditions.

Eosinophilic granulomatosis with polyangiitis: etiopathogenesis, classification and clinical phenotypes

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic disease that can be classified as both a hypereosinophilic condition and an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and is characterized by granulomatous inflammation. The pathogenesis of EGPA is not completely understood. It is likely that this disease is Th2-mediated, and blood and tissue eosinophilia serves as the main diagnostic criterion. The hallmarks and main effectors of organ damage in EGPA include asthma-associated necrotizing vasculitis of small-to-medium vessels and eosinophilic proliferation. Endothelial injury and vascular inflammation in EGPA is caused by ANCA via activation of circulating neutrophils. Two clinical phenotypes of the disease have been described based on the detection of ANCA: ANCA-negative with manifestations of hypereosinophilia (for example, pulmonary infiltrates and cardiomyopathy) and ANCA-positive with clinical signs of vasculitis (for example, glomerulonephritis, purpura, and mononeuritis multiplex). Both phenotypes were confirmed by histological and genomic research. However, these two coexisting mechanisms cannot be separated in clinical practice.The aim of the article is to present current knowledge of eosinophilic and ANCA-mediated aspects of the pathogenesis, classification and clinical phenotypes of EGPA, and consider prospects for future research.Conclusion. The development of EGPA is based on eosinophilic dysfunction. This dysfunction means that patients with a genetically determined predisposition to recognize the ANCA antigen and with HLA-DQ (human leukocyte antigen DQ) alleles produce anti-myeloperoxidase autoantibodies and later develop an aberrant autoimmune process. Further comprehensive post-genomic studies are needed to identify the pathogenetic mechanisms and characterize molecular features of EGPA clinical phenotypes. The elaboration of molecular endotypes will lead to the identification of new activity biomarkers and therapeutic targets that can improve the diagnosis of EGPA and the treatment outcomes.

The therapeutic validation of long COVID

The therapeutic validation of long COVID

NOD mouse dorsal root ganglia display morphological and gene expression defects before and during autoimmune diabetes development.

During the development of Autoimmune Diabetes (AD) an autoimmune attack against the Peripheral Nervous System occurs. To gain insight into this topic, analyses of Dorsal Root Ganglia (DRG) from Non-Obese Diabetic (NOD) mice were carried out. Histopathological analysis by electron and optical microscopy in DRG samples, and mRNA expression analyzes by the microarray technique in DRG and blood leukocyte samples from NOD and C57BL/6 mice were performed. The results showed the formation of cytoplasmic vacuoles in DRG cells early in life that could be related to a neurodegenerative process. In view of these results, mRNA expression analyses were conducted to determine the cause and/or the molecules involved in this suspected disorder. The results showed that DRG cells from NOD mice have alterations in the transcription of a wide range of genes, which explain the previously observed alterations. In addition, differences in the transcription genes in white blood cells were also detected. Taken together, these results indicate that functional defects are not only seen in beta cells but also in DRG in NOD mice. These results also indicate that these defects are not a consequence of the autoimmune process that takes place in NOD mice and suggest that they may be involved as triggers for its development.

Alzheimer’s Disease as an Autoimmune Disease

AbstractBackgroundThe identification of new exploitable molecular pathogeneses (beyond the conventional amyloid hypothesis) for Alzheimer’s disease (AD) is a continuing neurotherapeutic priority, and has yielded a range of mechanistic proposals including immunopathy, gliopathy, mitochondriopathy, synaptopathy. However, as these new hypotheses emerge, they are often regarded as mutually exclusive and even in competition. Rather than unconditionally rejecting the role of amyloid‐β (Aβ) (or any other proposed mechanism), the need for a broadly‐encompassing model of AD, which harmonizes multiple divergent theories into a single unified explanation emerges as a much‐needed goal.MethodWe performed a comprehensive series of in silico, in vitro and in vivo studies explicitly evaluating the atomistic‐molecular mechanisms of cytokine‐mediated and Aβ‐mediated neurotoxicities in AD. Next, new chemical entities were synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small molecule therapeutics.ResultIn response to various stimuli (e.g. infection, trauma, ischemia, air pollution, depression), Aβ is released as an early responder immunopeptide triggering an innate immunity cascade in which Aβ exhibits both immunomodulatory and antimicrobial properties (whether bacteria are present, or not), resulting in a misdirected attack upon ‘self’ neurons, arising from analogous electronegative surface topologies between neurons and bacteria, and rendering them similarly susceptible to membrane‐penetrating attack by antimicrobial peptides (AMPs) such as Aβ. Following this self‐attack, the resulting necrotic (but not apoptotic) neuronal breakdown products diffuse to adjacent neurons eliciting further release of Aβ, leading to a chronic self‐perpetuating autoimmune cycle. AD thus emerges as a brain‐centric autoimmune disorder of innate immunity. Based upon the hypothesis that autoimmune processes are susceptible to endogenous regulatory processes, a subsequent comprehensive screening program of small molecules normally present in human brain identified tryptophan metabolism as a regulator of brain innate immunity and a source of potential endogenous anti‐Alzheimer’s molecules capable of chemical modification into multi‐site therapeutic modulators targeting AD’s complex immunopathic‐proteopathic pathogenesis.ConclusionConceptualizing AD as a brain‐centric autoimmune disease of innate immunity (with Aβ as an immunopeptide), and identifying endogenous regulators of this autoimmunity, represents a novel comprehensive conceptualization approach to AD with therapeutic implications.

Role of miR-155 gene expression in Rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is prolonged, inflamed, and causes progressive disability, MicroRNAs appear to influence autoimmune disease processes through systemic consequences , including the immune system's irritant activities, in which specific antibodies with a high sensitivity for RA are the anti-CCP antibodies, Therefore, this research aims to evaluate the range of expression profile of circulating miRNA155 gene as a potential diagnostic biomarker in RA patients. The overall number comprised 36 RA patients, in addition to 14 healthy individuals as a comparison detection with ages ranging 20 to 60 years. All samples of patients and control suspected for diagnosed with anti-citrullinated protein antibodies test (ACPA) by immune assay for enzyme sorbent technique (ELISA). Relative quantification (RQ) of miRNA155 expression was performed after miRNA extraction from the serum of all study participants, was estimated using RT- qPCR. Significant Results noticed increased in expression of miRNA155 profile depending on the fold of expression (11.12 Fold expression ± 1.08), in comparison to a healthy people so as high significant (p ≤ 0.0001) of Anti-ccp Abs in patients with RA in which at risk and assessed the change in expression levels. In conclusion the study identified upregulation in circulated miRNA155 which may probably serve as prognostic form as biomarkers for disease in development.

Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus

Oral lichen planus (OLP) is considered a T cell-mediated chronic inflammatory process activated by an unknown antigen, making basal keratinocytes vulnerable to a cytotoxic cell mediated immune response. The aim of this review is to summarize information on the role and pathways of Epstein–Barr virus (EBV) and immune cells in inducing OLP as an autoimmune lesion. The pathogenesis of OLP is analyzed from immunological aspects of interactions between EBV and oral mucosa. The results of the available studies allow us to assume that EBV can act both as an exogenous and an endogenous antigen in the pathogenesis of OLP. We emphasized the role of antigen-presenting cells (APC), such as dendritic cells (Langerhans cells, LC), in detecting and capturing antigens and modulating the adaptive immune response. Although EBV shows tropism for B cells and epithelial cells, under certain conditions it can infect monocytes, LCs, NK, and T lymphocytes. It means that under some circumstances of the chronic inflammatory process, EBV particles can react as endogenous agents. During the development of the autoimmune process, a decisive role is played by the loss of immune tolerance. Factors like the activity of cytokines, chemokines, and autoantibodies secreted by EBV-positive plasma cells, autoantigens formed due to virus protein mimicry of human proteins, new self-peptides released from damaged tissues, self-reactive B and T cells, dysregulation of LC function, the anti-apoptotic effect of EBV early lytic antigens, and an imbalance between inflammatory and anti-inflammatory immune cells facilitate the development of an autoimmune process.