Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
32648858 Ultra-fast detection and quantification of nucleic acids by amplification-free fluorescenc 2020 Aug 24 Two types of clinically important nucleic acid biomarkers, microRNA (miRNA) and circulating tumor DNA (ctDNA) were detected and quantified from human serum using an amplification-free fluorescence hybridization assay. Specifically, miRNAs hsa-miR-223-3p and hsa-miR-486-5p with relevance for rheumatoid arthritis and cancer related mutations BRAF and KRAS of ctDNA were directly measured. The required oligonucleotide probes for the assay were rationally designed and synthesized through a novel "clickable" approach which is time and cost-effective. With no need for isolating nucleic acid components from serum, the fluoresence-based assay took only 1 hour. Detection and absolute quantification of targets was successfully achieved despite their notoriously low abundance, with a precision down to individual nucleotides. Obtained miRNA and ctDNA amounts showed overall a good correlation with current techniques. With appropriate probes, our novel assay and signal boosting approach could become a useful tool for point-of-care measuring other low abundance nucleic acid biomarkers.
34727697 IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW. 2020 Winter Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.
34724793 IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW. 2020 Winter Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans.
32305500 Chloroquine paradox may cause more damage than help fight COVID-19. 2020 May Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.
32239887 Follicular occlusion triad: an isotopic response or adverse effect of rituximab? 2020 Feb 15 Follicular occlusion triad is a symptom complex of three conditions with a similar pathophysiology including hidradenitis suppurativa (HS), dissecting cellulitis of the scalp, and acne conglobata. Although the exact pathogenesis of the triad is unknown, it appears to be related to follicular occlusion in areas with apocrine glands. Wolf isotopic response refers to the occurrence of a new dermatosis at the site of another, unrelated, previously healed dermatosis. We present a 26-year-old man with a history of pemphigus foliaceus (PF) who developed large draining nodules with scarring and sinus tracts, compatible with follicular occlusion triad, preferentially at areas previously affected by PF thirteen months after treatment with rituximab. To the authors' knowledge there are no reported cases of follicular occlusion triad or HS manifesting as an isotopic response. However, one member of the triad, HS, has been reported to occur infrequently following the use of biologic agents such as adalimumab, infliximab, tocilizumab, and rituximab for chronic immune-mediated inflammatory diseases (psoriasis, Crohn disease, rheumatoid arthritis, and ankylosing spondylitis).
31950440 Correction to: Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arth 2020 Mar The first name of the co-author of the above article was presented incorrect in the published version. The author name "Miangliang Qiu" should read "Mingliang Qiu" as mentioned above.
31495525 [Pyoderma gangrenosum and systemic lupus erythematosus: A rare association]. 2020 Jan INTRODUCTION: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is traditionally associated with systemic disorders such as chronic inflammatory bowel diseases, rheumatoid arthritis and malignant hematologic disorders. Its association with systemic lupus erythematosus (SLE) is rare and not well known. We report a case of this association with a review of the literature. CASE REPORT: A 43-year-old female patient, followed for 4 years for SLE, presented a deep ulceration of the anterior face of the left thigh with inflammatory borders, an ulcerated nodule of the right shoulder and four small ulcerations of the back of the right hand. The biopsy of the ulceration of the left thigh concluded to PG. The patient was treated by corticosteroids with complete healing of lesions. CONCLUSION: The prognosis of lupus does not seem to be aggravated by PG and the treatments of a SLE flare are usually enough for treating associated PG.
31427374 Multitasking Kinase RIPK1 Regulates Cell Death and Inflammation. 2020 Mar 2 Receptor-interacting serine threonine kinase 1 (RIPK1) is a widely expressed kinase that is essential for limiting inflammation in both mice and humans. Mice lacking RIPK1 die at birth from multiorgan inflammation and aberrant cell death, whereas humans lacking RIPK1 are immunodeficient and develop very early-onset inflammatory bowel disease. In contrast to complete loss of RIPK1, inhibiting the kinase activity of RIPK1 genetically or pharmacologically prevents cell death and inflammation in several mouse disease models. Indeed, small molecule inhibitors of RIPK1 are in phase I clinical trials for amyotrophic lateral sclerosis, and phase II clinical trials for psoriasis, rheumatoid arthritis, and ulcerative colitis. This review focuses on which signaling pathways use RIPK1, how activation of RIPK1 is regulated, and when activation of RIPK1 appears to be an important driver of inflammation.
33066667 The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function. 2020 Oct 14 Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mechanism of AhR signaling in regulating osteoclastogenesis is not widely understood. AhR, when binding with exogenous ligands (environmental pollutants such as polycylic aryl hydrocarbon (PAH), dioxins) or endogenous ligand indoxyl-sulfate (IS), has dual functions that are mediated by the nature of the binding ligand, binding time, and specific pathways of distinct ligands. In this review, AhR is discussed with a focus on (i) the role of AhR in osteoclast differentiation and function and (ii) the mechanisms of AhR signaling in inhibiting or promoting osteoclastogenesis. These findings facilitate an understanding of the role of AhR in the functional regulation of osteoclasts and in osteoclast-induced bone destructive conditions such as rheumatoid arthritis and cancer.
33063545 IgG4-negative pituitary inflammatory pseudotumor with sphenoidal involvement resembling a 2020 Oct 16 BACKGROUND: Inflammatory pseudotumors (IPTs) are rare benign conditions of unknown etiology that can affect any part of the body. IPTs are most commonly associated with Immunoglobulin G4 (IgG4)-related disease. Central nervous system IPTs, especially with pituitary involvement, are even rarer entities. The presence of an IgG4-negative pituitary IPT with simultaneous extracranial involvement has not been reported. CASE REPORT: We present the case of a 41-year-old female with past medical history of rheumatoid arthritis and a diagnosis of pituitary IPT with coexisting sphenoidal (extracranial) involvement mimicking a pituitary macroadenoma at presentation. The patient underwent multiple consecutive biopsies, and an extensive workup prior to establishing the diagnosis. Laboratory work-up showed normal serum IgG4 and unremarkable liver function tests. CONCLUSION: Pituitary lesions with simultaneous sphenoidal involvement in patients with IgG4-negative systemic inflammatory disease should raise the clinical suspicion for intracranial IPTs, as these tumors can mimic aggressive counterparts causing adjacent bony erosion, and local invasion.
32939516 From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity. 2020 Aug Sequence analyses highlight a massive peptide sharing between immunoreactive Epstein-Barr virus (EBV) epitopes and human proteins that-when mutated, deficient or improperly functioning-associate with tumorigenesis, diabetes, lupus, multiple sclerosis, rheumatoid arthritis, and immunodeficiencies, among others. Peptide commonality appears to be the molecular platform capable of linking EBV infection to the vast EBV-associated diseasome via cross-reactivity and questions the hypothesis of the "negative selection" of self-reactive lymphocytes. Of utmost importance, this study warns that using entire antigens in anti-EBV immunotherapies can associate with autoimmune manifestations and further supports the concept of peptide uniqueness for designing safe and effective anti-EBV immunotherapies.
32608358 [Bronchiectasis - a review]. 2020 Jul Bronchiectasis is a disease that is characterized by permanent bronchial dilation. This can be localized or diffuse in the lungs. The disease can occur at any age and causes cough, sputum production and repeated infections. It is more common in women and incidence increases with age. Bronchiectasis is characterized by repeated episodes of worsening symptoms that are usually caused by respiratory infections. The cause of bronchiectasis can be unknown but it can be caused by respiratory diseases and diseases outside the chest. Examples of such diseases are asthma, chronic obstructive pulmonary disease, rheumatoid arthritis in addition to immune deficiency. Disease profile is therefore different for each patient. Bronchiectasis is diagnosed with computerized tomography of the chest in addition to clinical symptoms. Workup to diagnose other diseases that could be causing it is therefore important. For that detailed history, physical examination and additional investigations are appropriate. Patients with bronchiectasis have decreased health related quality of life and increased mortality. Treatment focuses on treatment of underlying diseases, airway clearance and treatment of infections. Pulmonary rehabilititation is also important. Regular follow-up is important. This is a review on bronchiectasis that is intended for a spectrum of physicians, because bronchiectasis can be seen in primary care, hospitals and out of hospital.
32572805 Correction to: Anti-cyclic citrullinated peptide antibody in the cerebrospinal fluid in pa 2020 Aug The authors regret that the original published version of the above article contained errors. The authors requested that these be noted.
33425508 Post-Surgical Inflammatory Neuropathy: An Underappreciated but Critical and Treatable Caus 2020 Dec 5 The diagnosis and management of postoperative nerve injury can be a challenging and frustrating proposition for the patient, surgeon, and anesthesia provider. Unfortunately, in many cases, the true etiology is never elucidated and the injury is ascribed to positioning or a nerve block with "expectant management" being the order of the day, which can result in persistent disability for the patient. However, there is a rare subset of disorders affecting the nervous system that can masquerade as a peripheral nerve injury that warrants further investigation of risk factors and co-morbidities when other common causes of nerve injury are ruled out. We describe a patient with rheumatoid arthritis that underwent revision hip arthroplasty and presented almost immediately in the postoperative period with what was initially diagnosed as femoral nerve palsy. Further diagnostic workup later revealed that she had suffered from postoperative inflammatory neuropathy resulting in lumbosacral plexus injury and not a discrete nerve injury. Had the true cause been identified early enough, treatment with corticosteroids could have been initiated in an attempt to mitigate and perhaps reverse the progress of the neuropathy. We present this cautionary tale to remind practitioners to continue to be vigilant and consider more esoteric and unconventional diagnoses in the workup of perioperative neuropathies.
33296970 CNS demyelination during tofacitinib therapy: First report. 2020 Nov Iatrogenic demyelination is a distinct clinical subtype of central nervous system inflammatory disorders. The Janus kinase inhibitor, tofacitinib, is an oral disease-modifying antirheumatic drug that has shown contradictory effects on multiple sclerosis in animal models. In this report, we describe a novel case of reversible multifocal CNS demyelination in a patient with seropositive rheumatoid arthritis on tofacitinib. Although the mechanism is not completely understood, activation of T17 cells by tofacitinib and the subsequent increased production of interleukin-17 could be the cause. Moreover, a link between TNF-α and JAK/STAT pathways has been suggested, which may further explain the occurrence of iatrogenic demyelination in this case.
33162505 [The pathogenesis of anemia in inflammation]. 2020 Inflammation is a physiological process that primarily occurs as a way to help protect the host against tissue damage and invasion by pathogens. During inflammation, erythropoiesis is suppressed and, if it lasts, anemia develops. The mechanisms underlying this are complex and not fully understood, but various cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and IL-6, are involved. TNF-α upregulates PU.1, which is a crucial transcription factor in granulocytic differentiation, and downregulates GATA-1, a master transcription factor for erythroid differentiation, in hematopoietic stem cells. TNF-α and IL-1β suppress erythropoietin production in the kidney, whereas IFN-γ downregulates the expression of erythropoietin receptors in erythroid precursor cells. Moreover, IL-6 upregulates the production of hepcidin, the master regulator of systemic iron metabolism, in the liver. Hepcidin reduces the iron available for erythropoiesis by downregulating the rate of iron release from macrophages. Activated macrophages may also contribute to the development of anemia by shortening the erythrocyte lifespan. Proper management of the underlining conditions is necessary in treating anemia associated with inflammation. Erythropoiesis-stimulating agents may be administered to patients with chronic kidney disease, whereas anti-IL-6 agents may be beneficial for anemic patients with rheumatoid arthritis and idiopathic multicentric Castleman disease.
33036119 A 47-Year-Old Woman With Pulmonary Nodules and Facial Hemispasms. 2020 Oct A 47-year-old woman visited her primary physician for a health check, and some radiographic abnormalities were detected. She was referred to our division for further management. In recent years, she had become conscious of occasional facial hemispasms. She denied respiratory symptoms, smoking, alcohol consumption, and any particle inhalation. She had undergone oophorectomy and platinum-based chemotherapy because of ovarian cancer (serous cystadenocarcinoma stage â… a) at the age of 29 years, with no recurrence for 17 years. The patient was diagnosed with rheumatoid arthritis (RA) 5 years before being seen by us and had been treated with bucillamine. No signs of RA progression were evident, and the only used antirheumatic drug was bucillamine. The patient had no history of use of immune-modulating drugs or immunosuppressants. No previous chest radiographs or CT had been performed.
33010903 Mindfulness, Stress, and Aging. 2020 Nov Mindfulness has been applied in several adaptations, including Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy, to treat chronic conditions in older adults. Older adults may be particularly well suited for mindfulness interventions, because they bring decades of life experience to this contemplative therapy. Mindfulness is also an appealing intervention for older adults as it is inexpensive, effective over time, and easy to access. This article examines mental and physical chronic conditions proven responsive to mindfulness, including cognitive function, anxiety, depression, sleep quality, loneliness, posttraumatic stress disorder, cardiovascular conditions, diabetes, rheumatoid arthritis, Parkinson's disease, urge urinary incontinence, and chronic pain.
32984346 Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N(6)-Methyladenos 2020 RNA modifications have emerged as key regulators of transcript expression in diverse physiological and pathological processes. As one of the most prevalent types of RNA modifications, N(6)-methyladenosine (m(6)A) has become the highlight in modulation of various diseases through interfering RNA splicing, translation, nuclear export, and decay. In many cases, the detailed functions of m(6)A in cellular processes and diseases remain unclear. Notably, recent studies have determined the relationship between m(6)A modification and musculoskeletal disorders containing osteosarcoma, osteoarthritis, rheumatoid arthritis, osteoporosis, etc. Herein, this review comprehensively summarizes the recent advances of m(6)A modification in pathogenesis and progression of musculoskeletal diseases. Specifically, the underlying molecular mechanisms, detection technologies, regulatory functions, clinical implications, and future perspectives of m(6)A in musculoskeletal disorders are discussed, with the aim to provide a novel insight into their association.
32849178 Myasthenia Gravis and Physical Exercise: A Novel Paradigm. 2020 The benefits of physical exercise for healthy individuals are well-established, particularly in relation to reducing the risks of chronic lifestyle related diseases. Furthermore, physical exercise has been seen to provide beneficial effects in many chronic diseases such as multiple sclerosis, rheumatoid arthritis, and chronic obstructive pulmonary disease and is therefore recommended as part of the treatment regimen. Myasthenia Gravis (MG) is a chronic autoimmune disease that causes neuromuscular transmission failure resulting in abnormal fatigable skeletal muscle weakness. In spite of this fluctuating skeletal muscle weakness, it is reasonable to assume that MG patients, like healthy individuals, could benefit from some of the positive effects of physical exercise. Yet exercise-related research in the field of MG is sparse and does not provide any guidelines on how MG patients should perform physical training in order to obtain exercise's favorable effects without risking disease deterioration or more pronounced muscle fatigue. A handful of recent studies report that MG patients with mild disease activity can adhere safely to general exercise recommendations, including resistance training and aerobic training regimens, without subjective or objective disease deterioration. These findings indicate that MG patients can indeed improve their functional muscle status as a result of aerobic and high-resistance strength training. This knowledge is important in order to establish collective as well as personalized guidelines on physical exercise for MG patients. This review discusses the present knowledge on physical exercise in MG.