scholarly journals Phage display identification of immunodominant epitopes and autoantibodies in autoimmune diseases

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Marco Palma
Keyword(s):  
Autoimmune Diseases ◽  
Phage Display ◽  
Lupus Erythematosus ◽  
Clinical Signs ◽  
Immunosuppressive Drugs ◽  
Antigenic Structure ◽  
Therapeutic Approaches ◽  
Invaluable Tool ◽  
Epitope Sharing ◽  
Immunodominant Epitopes

Phage display represents an invaluable tool to study autoimmune diseases. The side effects of immunosuppressive drugs for the treatment of autoimmune diseases raise awareness of the need to explore alternative therapeutic approaches such as antibodies and peptides. Therefore, phage display is an important technique for generating such molecules, so the purpose of this review is to determine the potential advantages of this technique in the research of autoimmune diseases. Many studies have also demonstrated the efficacy of phage display in identifying immunodominant epitopes of autoimmune diseases such as Goodpasture disease, immunologic thrombocytopenia, and systemic lupus erythematosus. Phage display peptide libraries have been screened with immunopurified autoantibodies from patients with autoimmune diseases. This makes it possible to more precisely locate the autoantibody binding sites, reveal a possible epitope sharing between the host and microbe, and identify a motif that mimics an antigenic structure such as that of dsDNA. Several studies have been conducted that have investigated the effectiveness of phage display in isolating autoantibody repertoires of autoantibodies against human epitopes. This allows the identification and design of antibody fragments (e.g., Fab, scFv, sdAb) that could block the binding of autoantibodies such as the deposition of IgG in the kidney and reduce the clinical signs of disease. In conclusion, phage display helps identify common epitopes and hotspot residues that can be potential therapeutic targets for the treatment of autoimmune diseases. This leads to a better understanding of the immunopathogenesis of autoimmune diseases and the development of more specific therapeutic strategies.

scholarly journals Current Paradigms of Tolerogenic Dendritic Cells and Clinical Implications for Systemic Lupus Erythematosus

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1291 ◽  
Author(s):  
Ritprajak ◽  
Kaewraemruaen ◽  
Hirankarn
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Ex Vivo ◽  
Immunosuppressive Drugs ◽  
Clinical Implications ◽  
Systemic Lupus ◽  
Tolerogenic Dendritic Cells

Tolerogenic dendritic cells (tolDCs) are central players in the initiation and maintenance of immune tolerance and subsequent prevention of autoimmunity. Recent advances in treatment of autoimmune diseases including systemic lupus erythematosus (SLE) have focused on inducing specific tolerance to avoid long-term use of immunosuppressive drugs. Therefore, DC-targeted therapies to either suppress DC immunogenicity or to promote DC tolerogenicity are of high interest. This review describes details of the typical characteristics of in vivo and ex vivo tolDC, which will help to select a protocol that can generate tolDC with high functional quality for clinical treatment of autoimmune disease in individual patients. In addition, we discuss the recent studies uncovering metabolic pathways and their interrelation intertwined with DC tolerogenicity. This review also highlights the clinical implications of tolDC-based therapy for SLE treatment, examines the current clinical therapeutics in patients with SLE, which can generate tolDC in vivo, and further discusses on possibility and limitation on each strategy. This synthesis provides new perspectives on development of novel therapeutic approaches for SLE and other autoimmune diseases.

scholarly journals A mikro-RNS-ek jelentősége szisztémás autoimmun betegségek kialakulásában

2019 ◽  
Vol 160 (15) ◽  
pp. 563-572 ◽  
Author(s):  
Ilona Jámbor ◽  
Krisztina Szabó ◽  
Margit Zeher ◽  
Gábor Papp
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Cell Lineage ◽  
Therapeutic Approaches ◽  
Systemic Autoimmune Diseases ◽  
Protein Coding ◽  
Diagnosis And Prognosis ◽  
Research Findings ◽  
Posttranscriptional Level

Abstract: MicroRNAs (miRNAs) are 18–25 nucleotide long, single stranded, endogenous, non-coding small RNAs playing an important role in regulating gene expression at posttranscriptional level. miRNAs control approximately 90% of protein-coding genes, and play a central role in various biological processes including immune cell lineage commitment, differentiation, proliferation, apoptosis and maintenance of immune homeostasis. Changes in the expression of certain miRNAs may lead to the development of many diseases, including systemic autoimmune diseases. In this study, we summarize the biogenesis of miRNAs, their role in regulation of the immune system, and review the latest research findings in systemic lupus erythematosus, primary Sjögren’s syndrome, rheumatoid arthritis and systemic sclerosis. In the future, miRNAs may help not only in establishing diagnosis and prognosis but potentially serve as targets for modern therapeutic approaches in autoimmune diseases. Orv Hetil. 2019; 160(15): 563–572.

scholarly journals Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3621-3625 ◽  
Author(s):  
HH Euler ◽  
AM Marmont ◽  
A Bacigalupo ◽  
S Fastenrath ◽  
P Dreger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autoimmune Disease ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Lupus Erythematosus ◽  
Clinical Signs ◽  
High Dose

Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases.

scholarly journals Current advances in the treatment of autoimmune-associated interstitial lung diseases

2021 ◽  
Vol 64 (4) ◽  
pp. 264-276
Author(s):  
Sunggun Lee ◽  
Jae Ha Lee
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Immunosuppressive Agents ◽  
Interstitial Lung Diseases ◽  
Limited Data ◽  
Therapeutic Approaches ◽  
Inflammatory Myositis ◽  
Clinically Significant ◽  
High Level

Autoimmune-associated interstitial lung disease (ILD) is a widespread and clinically significant form of autoimmune diseases. ILD can be present in most type of autoimmune diseases. Scleroderma, Sjogren syndrome, rheumatoid arthritis, inflammatory myositis, systemic lupus erythematosus, and mixed connective tissue disease are all examples of autoimmune disorders that can cause ILD. Treatment and prognosis vary from that of other forms of ILD depending on the etiology and pathogenesis of the autoimmune disease. As a result, glucocorticoids and immunosuppressive agents are the mainstays of treatment for autoimmune-associated ILD, despite the fact that there is little high-level evidence to guide the treatment owing to limited data from randomized controlled trials. Immunosuppressive agents including cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil can be used to reduce the dose of glucocorticoids and the inflammatory cascade and inhibit various pro-inflammatory cytokines. Studies have also started alternative therapeutic approaches, such as biological and antifibrotic agents, and traditional immunosuppressive agents. In this review, we summarize available treatment options and recent advances in therapeutic strategies for patients with autoimmune-associated ILD.

scholarly journals Contemporary aspects on the immunopathogenesis of autoimmune diseases of the epidermal basement membrane in the dog

2017 ◽  
Vol 56 (1) ◽  
pp. 27
Author(s):  
E. I. PAPADOGIANNAKIS (E. Ι. ΠΑΠΑΔΟΓΙΑΝΝΑΚΗΣ)
Keyword(s):  
Basement Membrane ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Skin Diseases ◽  
Clinical Signs ◽  
Molecular Techniques ◽  
Mucous Membrane Pemphigoid ◽  
Linear Iga Dermatosis ◽  
Specific Antigens ◽  
Epidermal Basement Membrane

Autoimmune diseases of the epidermal basement membrane are the result of the immune system self-activation against specific antigens of its essential structural elements. This group of skin diseases is characterized by the destruction of connecting bonds between the membrane zone and dermis, which eventually leads to the dermoepidermal separation and the formation of subepidermal vesicles and bullae. In this article, the immunopathogenesis and the clinical, histopathological and immunohistochemical features of each of these skin diseases are briefly reviewed. The autoimmune diseases of the canine epidermal basement membrane have been recently classified as bullous pemphigoid, mucous membrane pemphigoid, linear IgA dermatosis, epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Recent advances in immunopathological and molecular techniques have markedly facilitated the understanding of their pathogenesis, thus giving the opportunity for the development of new therapeutic strategies that may improve or eliminate the clinical signs.

scholarly journals Bacterial molecular mimicry in autoimmune diseases

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Marco Palma
Keyword(s):  
Autoimmune Diseases ◽  
Phage Display ◽  
Chlamydia Pneumoniae ◽  
Molecular Mimicry ◽  
Fc Receptors ◽  
Immunosuppressive Drugs ◽  
Cross Reactivity ◽  
Antibody Fragments ◽  
Local Alignment ◽  
Atherosclerotic Vascular Disease

Bacterial molecular mimicry in autoimmune diseases is one of the leading mechanisms by which microorganisms may induce autoimmunity and survive in the host. The main purpose of the current study was to determine the main microbes that elicit autoimmune reactions through molecular mimicry and identify the most relevant approaches to investigate this mechanism. A classic example is the M protein of Streptococcus pyogenes, which induces antibody cross-reactivity with a cardiac protein and causes rheumatic fever. Another notable example is the protein from Porphyromonas gingivalis that closely resembles the human heat shock protein and accelerates atherosclerotic. There is evidence that antibodies against Helicobacter pylori CagA interact with different parts of smooth muscle and endothelial cells enhancing atherosclerotic vascular disease. Recently, one cause of infertility has been associated with Staphylococcus aureus molecular mimicry that triggers an antibody response that cross-reacts with human spermatozoa proteins. Further examples of bacterial molecular mimicry are associated with Chlamydia pneumoniae, Escherichia coli, Yersinia, and Salmonella. From the literature, the most widely used methods in this field are Basic Local Alignment Search Tool (BLAST), serological assays, and phage display. The subjects of particular concern are vaccine cross-reactivity and immunosuppressive drugs side-effects, therefore alternative approaches are needed. Such an approach is phage display where therapeutic antibody fragments obtained by this technique have been used in the treatment of autoimmune diseases by neutralizing the pathological effects of autoantibodies. Phage display libraries are constructed from the antibody repertoires of autoimmune disease patients. Antibody fragments without the Fc domain can not interact with Fc receptors and proteins of the complement system and trigger autoimmune diseases. Another approach is to block the Fc receptors. In conclusion, this review highlights key aspects of bacterial molecular mimicry to better understand the factors associated with autoimmune diseases and encourage further research in this field.

scholarly journals Bortezomib in antibody-mediated autoimmune diseases (TAVAB): study protocol for a unicentric, non-randomised, non-placebo controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e024523 ◽  
Author(s):  
Siegfried Kohler ◽  
Stefanie Märschenz ◽  
Ulrike Grittner ◽  
Tobias Alexander ◽  
Falk Hiepe ◽  
...  
Keyword(s):  
Side Effects ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Case Reports ◽  
Controlled Trial ◽  
Neuropsychological Testing ◽  
Significant Proportion ◽  
Clinical Signs ◽  
Specific Treatment ◽  
Experimental Models

IntroductionThe clinical characteristics of autoantibody-mediated autoimmune diseases are diverse. Yet, medical treatment and the associated complications are similar, that is, the occurrence of long-term side effects and the problem that a significant proportion of patients are non-responders. Therefore, new therapeutic options are needed. Bortezomib, a proteasome inhibitor, is effective in the treatment of multiple myeloma and data from experimental models and case reports suggest an effect in the treatment of autoantibody-mediated autoimmunity. In our study, we will determine the effect of bortezomib treatment on a shared surrogate parameter for clinical efficacy, namely change in autoantibody levels, which we chose as primary parameter.Methods and analysisWe designed a phase IIa trial with altogether n=18 treatment-refractory patients suffering from myasthenia gravis, systemic lupus erythematosus and rheumatoid arthritis that will be treated with bortezomib add-on to pre-existing therapy. Primary endpoint is the change in autoantibody levels 6 months after therapy. Secondary endpoints include concomitant medication, disease-specific clinical scores and measures of quality of life and activities of daily living.Ethics and disseminationSafety parameters include neurophysiological and clinical signs of peripheral neuropathy as well as potential central nervous system side effects determined by olfactory and neuropsychological testing. The study has been approved by the local ethical committee and first participants have already been enrolled. This proof of concept study will contribute to improve our understanding of plasma cell-specific treatment approaches by assessing its safety and efficacy in reducing serum levels of antibodies known to mediate autoimmune disorders.We plan to publish the final results of our study in a peer reviewed journal and to present our findings at international conferences.Trial registration numberNCT02102594.

scholarly journals Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice

2004 ◽  
Vol 199 (11) ◽  
pp. 1577-1584 ◽  
Author(s):  
Bimba F. Hoyer ◽  
Katrin Moser ◽  
Anja E. Hauser ◽  
Anette Peddinghaus ◽  
Caroline Voigt ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Immunosuppressive Drugs ◽  
Current View ◽  
Humoral Autoimmunity ◽  
Auto Antibody ◽  
Ig Heavy Chain ◽  
B And T Lymphocytes ◽  
Antibody Secreting Cells

The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressive drugs designed to interfere with this activation the production of autoantibodies often persists and contributes to progression of the immunopathology. In the present study, we analyzed the life span of (auto)antibody-secreting cells in the spleens of NZB × NZW F1 (NZB/W) mice, a murine model of systemic lupus erythematosus. The number of splenic ASCs increased in mice aged 1–5 mo and became stable thereafter. Less than 60% of the splenic (auto)antibody-secreting cells were short-lived plasmablasts, whereas 40% were nondividing, long-lived plasma cells with a half-life of >6 mo. In NZB/W mice and D42 Ig heavy chain knock-in mice, a fraction of DNA-specific plasma cells were also long-lived. Although antiproliferative immunosuppressive therapy depleted short-lived plasmablasts, long-lived plasma cells survived and continued to produce (auto)antibodies. Thus, long-lived, autoreactive plasma cells are a relevant target for researchers aiming to develop curative therapies for autoimmune diseases.

scholarly journals Lupus Erythematosus and Chronic Granulomatous Disease: Report of Four Iranian Patients with AR-CGD and One XL-CGD

2019 ◽  
Author(s):  
Marzieh Maddah ◽  
Mohammad Reza Fazlollahi ◽  
Reza Shiari ◽  
Farhad Shahram ◽  
Setareh Mamishi ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Granulomatous Disease ◽  
Lupus Erythematosus ◽  
Genetic Disorder ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Granulomatous Disease ◽  
Clinical Signs And Symptoms ◽  
Bacteria And Fungi

Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase–positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X–linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow–up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results.

Immune Thrombocytopenia in an Adolescent with Hashimoto’s Thyroiditis – Case Report

2019 ◽  
Vol 4 (3) ◽  
pp. 145-149 ◽  
Author(s):  
Izabella Kelemen ◽  
Zsuzsanna Erzsébet Papp ◽  
Mária Adrienne Horváth
Keyword(s):  
Platelet Count ◽  
Autoimmune Diseases ◽  
Hashimoto’S Thyroiditis ◽  
Clinical Signs ◽  
Immunoglobulin Therapy ◽  
Peripheral Blood Smear ◽  
Bleeding Complications ◽  
Hashimoto's Thyroiditis ◽  
Line Treatment ◽  
First Line

Abstract Introduction: In childhood, thrombocytopenia caused by transient antibody-mediated thrombocyte destruction is most frequently diagnosed as immune thrombocytopenic purpura (ITP). We report the case of a girl with ITP associated with autoimmune thyroiditis. Case presentation: A 11-year-old female patient with Hashimoto’s thyroiditis presented with clinical signs of petechiae and ecchymoses on the extremities. Laboratory tests showed remarkable thrombocytopenia with a platelet count of 44,500/μL, hence she was referred to a hematologic consultation. The peripheral blood smear showed normal size platelets in very low range. The bone marrow examination exposed hyperplasia of the megakaryocyte series with outwardly morphologic abnormalities. The patient was diagnosed with ITP, and her first-line treatment was pulsed steroid and immunoglobulin therapy. The thrombocytopenia was refractory to these first-line medications. After 6 months of corticotherapy and a period of severe menorrhagia, azathioprine immunosupression was initiated as a second-line treatment. Her platelet count rapidly increased, and the evolution was good, without bleeding complications. Conclusion: In case of a medical history of autoimmune diseases and treatment-resistant ITP, attention must be focused on detecting coexisting autoimmune diseases and adjusting the treatment in accordance with the chronic evolution of the disease.

Sign in / Sign up

Export Citation Format

Share Document