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 Tocilizumab for the Treatment of Rheumatoid Arthritis and Other Systemic Autoimmune Diseases: Current Perspectives and Future Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Atsushi Ogata ◽  
Toshio Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Host Defense ◽  
Lupus Erythematosus ◽  
Therapeutic Strategy ◽  
Case Reports ◽  
Systemic Autoimmune Diseases ◽  
Future Directions ◽  
Pilot Studies ◽  
Beneficial Effects

Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis.

scholarly journals Mupirocin Pemphigus-Like Drug Reaction in a Dog

2019 ◽  
Vol 47 ◽  
Author(s):  
Tiago Cunha Ferreira ◽  
Rodrigo Fonseca De Medeiros Guedes ◽  
Belise Maria Oliveira Bezerra ◽  
Diana Célia Sousa Nunes-Pinheiro
Keyword(s):  
Side Effects ◽  
Autoimmune Diseases ◽  
Clinical Signs ◽  
Inguinal Region ◽  
Pemphigus Foliaceus ◽  
High Dose ◽  
Azathioprine Therapy ◽  
Dermatological Examination ◽  
Days Of Therapy ◽  
Triggering Factor

Background: Pharmacodermia is defined as adverse reaction in skin, mucosa and appendages, which generates morpho-functional alterations in cutaneous barrier, inducing autoimmune diseases, such as pemphigus foliaceous, which is known as the most common autoimmune skin disease in dogs. This disease involves autoantibodies against desmoglein and desmocolin molecules, being induced by the use of certain drugs. Mupirocin (pseudomonic acid A) is a broad-spectrum antibiotic with bacteriostatic activity, being effective against Gram-positive pathogens and used to control superficial bacterial folliculitis. Based on that, the aim of this study was to report a pemphigus-like lesions after topical use of mupirocin in dog.Case: An 1-year-old, uncastrated male, Poodle dog, weighing 13.8 kg was treated in a private clinic in Fortaleza. The main complaint was related to pruritus in abdominal and inguinal region, in addition of legs licking. Dermatological examination revealed melanic crusts, epidermal collars and diffuse pustules in inguinal, abdominal, perianal and thoraco-lumbar regions. The therapy was based on topical use of Mupirocin in form of 0.2% aquous spray. After drug administration, the animal presented urticaria, diffuse epidermal collars, papulo-crusted and pustular lesions, which were more evident in abdominal and inguinal region. Nasal erythema, binocular blepharitis, apathy and fever were also observed. Cytological examination and bacterial culture were performed, revealing inflammatory and acantholytic cells and no bacterial growth. Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigus foliaceous. The topical treatment of ocular lesions with 0.1% Tacrolimus associated with systemic treatment with high dose of prednisolone (1.2 mg kg-1). The patient improved the dermatological clinical signs, however, some side effects have already become evident, such as the presence of telangiectasia, polyuria, polyphagia and polydipsia. Heterodox therapy based on the use of azathioprine (2 mg kg-1) was chosen in order to reduce corticoid dose. After 3 days of therapy, blood material was collected for hepatic evaluation, detecting hepatotoxicity. From the results, azathioprine therapy was suspended, and only high-dose corticosteroid therapy (1.5 mg kg-1) was maintained. The patient presented a considerable improvement in the lesion after 10 days of treatment.Discussion: There have been reports that pharmacodermic reactions may be associated with the development of autoimmune diseases, such as pemphigus foliaceus and vulgaris. In some cases, the lesions regress after drug discontination. In others, the medication acts as a triggering factor, activating the genetic predisposition of patient, which develops the pathology even after therapy interruption. The drug related pemphigus-foliaceous is a well-recognized disease in humans, however this disease is limited to sporadic cases in dogs. The therapy was based in use of a high dose of prednisolone, which caused some side effects. Therefore, a heterodox therapy was chosen in order to reduce the corticoid dosage. At the first hemato-biochemical evaluation, the patient already presented significant alterations, being requested to suspend the prescribed treatment, although the owners already reported improvement of the dermatological lesions. Due to this, a higher dose of prednisolone was chosen, obtaining the best response among the therapies used since the beginning of the treatment. After clinical improvement, the gradual reduction of steroidal therapy was started in order to avoid side effects related to suppression of the hypothalamic-pituitary-adrenal axis. This report provides evidences of Mupirocin as a potential triggering factor of pemphigus-like lesions in dogs.

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 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 Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1013 ◽  
Author(s):  
Rossana Scrivo ◽  
Carlo Perricone ◽  
Alessio Altobelli ◽  
Chiara Castellani ◽  
Lorenzo Tinti ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Clinical Studies ◽  
Dietary Habits ◽  
Salt Intake ◽  
Experimental Models ◽  
Fine Tuning ◽  
Current Evidence

The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn’s disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity.

scholarly journals Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

2009 ◽  
Vol 2009 ◽  
pp. 1-20 ◽  
Author(s):  
Manfred Kunz ◽  
Saleh M. Ibrahim
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Expression Patterns ◽  
Specific Treatment ◽  
Systemic Lupus ◽  
Treatment Approaches ◽  
New Genes ◽  
New Treatment

The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL)-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

scholarly journals Psychiatric side effects induced by chloroquine and hydroxychloroquine: a systematic review of case reports and population studies

2020 ◽  
Author(s):  
Fernanda Talarico ◽  
Sucheta Chakravarty ◽  
Yang S. Liu ◽  
Andrew Greenshaw ◽  
Ives Cavalcante Passos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Lupus Erythematosus ◽  
Psychotic Disorders ◽  
Suicide Attempts ◽  
Population Studies ◽  
Psychiatric Symptoms ◽  
Case Reports ◽  
Psychomotor Activity ◽  
Psychiatric Side Effects

AbstractChloroquine and hydroxychloroquine are commonly used drugs in the treatment of malaria as well as chronic diseases, such as rheumatoid arthritis, and systemic lupus erythematosus. Although various reports on possible psychiatric side effects of these drugs exist, the nature and extent of these effects remain poorly understood. Moreover, the relevance of these drugs in the treatment of early stages of COVID-19 necessitates a careful estimation of their side effects. Here, we provide a systematic review of the psychiatric side effects associated with chloroquine and hydroxychloroquine. We used PubMed, Scopus, and Web of Science platforms to identify relevant literature published between 1962 and 2020. Search terms included chloroquine, hydroxychloroquine, psychiatry, psychosis, depression, anxiety, bipolar disorder, delirium, and psychotic disorders. Only case reports and clinical trials were included. All studies included records of psychiatric side effects induced by either chloroquine or hydroxychloroquine or both. Both retrospective and prospective, randomized as well as non-randomized population studies were included. Overall, the psychiatric side effects are dose- and sex-independent. The most common psychiatric side effects reported are increased speech output/ excessive talking, increased psychomotor activity, irritable mood, auditory hallucinations, delusion of grandiosity, and suicide attempts, likely due to brain intoxicationbe of chloroquine or hydroxychloroquine. The symptoms can develop in a few hours to 11 weeks after drug intake and are normally reversed within a week after the drug withdrawal. We conclude that CQ and HCQ have the potential to induce psychiatric side effects. This study calls for further investigation of psychiatric symptoms induced by these drugs in the short and long term.

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 Autoimmune Diseases in Patients with Cushing’s Syndrome after Resolution of Hypercortisolism: Case Reports and Literature Review

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Luigi Petramala ◽  
Federica Olmati ◽  
Maria Gabriella Conforti ◽  
Antonio Concistré ◽  
Valeria Bisogni ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Cushing’S Syndrome ◽  
Lupus Erythematosus ◽  
Case Reports ◽  
Cushing's Syndrome ◽  
Secondary Hypertension ◽  
Metabolic Complications ◽  
Ectopic Acth ◽  
Ectopic Acth Production

Introduction. Cushing’s syndrome (CS) is a clinical condition characterized by excessive cortisol production, associated with metabolic complications, such as diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, and cardiovascular diseases. Nowadays, the occurrence of autoimmune diseases in CS have not been completely evaluated in the previous studies. Objective. The aim of this study was to evaluate the occurrence of autoimmune diseases in CS patients after successfully treated. Materials and Methods. From January 2001 to December 2017, in our Secondary Hypertension Unit, we evaluated 147 CS patients (91 with ACTH-independent disease, 54 with ACTH-dependent disease, and 2 patients with ectopic ACTH production. Results. 109 CS patients (74.1%) were surgically treated (67 ACTH-independent CS patients (61.5%) undergone adrenalectomy and 42 ACTH-dependent CS (38.5%) undergone transsphenoidal surgery) and evaluated after 6, 12, and 24 months after clinical and biochemical remission of disease. In 9 (8.3%) of overall treated CS patients (8.3%), during follow-up, we observed the onset of some manifestations of autoimmune diseases. In particular, one patient had a systemic lupus erythematosus, one patient had rheumatoid arthritis, 4 patients reported autoimmune thyroiditis (Basedow-Graves’ disease and Hashimoto’s thyroiditis), one patient had clinical features of psoriasis, one patient showed myasthenia gravis, and one patient had giant cell arteritis. Conclusions. Our results demonstrate that patients successfully treated for CS could develop autoimmune diseases. Therefore, after treatment, CS patients need to be strictly monitored in order to evaluate the possible onset of 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.

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