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ID PMID Title PublicationDate abstract
31683054 A novel NFKBIA variant substituting serine 36 of IκBα causes immunodeficiency with warts 2020 Jan Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.
33003234 [Arthrodesis of the Upper Ankle and Subtalar Joint - Indication and Technique]. 2021 Jun Arthrodesis of the upper ankle and subtalar joint are still frequently used and at the moment the gold standard in the therapy of severe arthritis and deformity of the ankle joint and hindfoot. The spectrum of indications is wide, beginning from posttraumatic or degenerative changes to postinfectious, rheumatoid and diabetic causes of arthritis and as a salvage procedure after failed ankle arthroplasty. The types of arthrodesis have to be differentiated from each other: tibiotalar, subtalar and tibiotalcalcaneal fusion. Soft tissue conditions have to be taken into account; these and individual factors like comorbidities and osseous conditions require an individual planning of the approaches and types of fixation.
33521571 The Differential Effect of Antibodies on Radiographic Progression in Rheumatoid Arthritis. 2020 Dec BACKGROUND/OBJECTIVES: The presence of bony erosions in patients with RA is a marker of disease severity and once present they are largely irreversible. Previous studies have shown that the presence of both rheumatoid factor (RF) and anti-cyclic citrullinated peptide (ACPA) antibodies is associated with erosive burden. The aim of our study is to determine the strength of relationship between antibody status and the presence of radiographic erosions at diagnosis. METHODS: A retrospective study of patients diagnosed with RA at a large university teaching hospital between January 1981 and December 2018. Clinical records were reviewed to determine antibody status, diagnosis date, duration of symptoms, DAS-28, age, ethnicity and whether the 1987 RA criteria was met. The presence of erosions at diagnosis were determined from plain film radiographs reports of hands and feet of patients. Statistical analysis was done using a Chi Square Model and Mann Whitney two-tailed U test. RESULTS: There were 774 patients diagnosed with RA in our cohort. 367 (47%) of them were RF+/ACPA+, 87 (11%) were RF+/ACPA-, 66 (9%) were RF-/ACPA+ and 254 (33%) were antibody negative. 127 patients had erosions at the time of diagnosis. Patients in the double positive group had a significantly higher (p=0.003) erosion burden compared to the double negative group i.e. 21.5% in RF+/ACPA+ versus 11.0% in RF-/ACPA- group. The erosion burdens in RF+/ACPA- and RF-/ACPA+ groups were 13.7% and 12.1% respectively. CONCLUSIONS: Our results show that patients RF+/ACPA+ have nearly two-fold higher incidence of radiographic erosions than patients who are RF-/ACPA-.
33488588 Epstein-Barr Virus and Systemic Autoimmune Diseases. 2020 Epstein-Barr Virus (EBV) is an extremely successful human herpes virus, which infects essentially all human beings at some time during their life span. EBV infection and the associated immune response results in production of antibodies (seroconversion), which occurs mainly during the first years of life, but may also happen during adolescence or later in life. Infection of adolescents can result in infectious mononucleosis, an acute serious condition characterized by massive lymphocytosis. Transmission of EBV mainly occurs through saliva but can rarely be spread through semen or blood, e.g. through organ transplantations and blood transfusions. EBV transmission through oral secretions results in infection of epithelial cells of the oropharynx. From the epithelial cells EBV can infect B cells, which are the major reservoir for the virus, but other cell types may also become infected. As a result, EBV can shuttle between different cell types, mainly B cells and epithelial cells. Moreover, since the virus can switch between a latent and a lytic life cycle, EBV has the ability to cause chronic relapsing/reactivating infections. Chronic or recurrent EBV infection of epithelial cells has been linked to systemic lupus erythematosus and Sjögren's syndrome, whereas chronic/recurrent infection of B cells has been associated with rheumatoid arthritis, multiple sclerosis and other diseases. Accordingly, since EBV can shuttle between epithelial cells and B cells, the systemic autoimmune diseases often occur as overlapping syndromes with symptoms and characteristic autoantibodies (e.g. antinuclear antibodies and rheumatoid factors) reflecting epithelial and/or B cell infection.
33132897 Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. 2020 Neurodegenerative diseases are characterized by the loss of neurons and/or myelin sheath, which deteriorate over time and cause dysfunction. Interleukin 17A is the signature cytokine of a subset of CD4(+) helper T cells known as Th17 cells, and the IL-17 cytokine family contains six cytokines and five receptors. Recently, several studies have suggested a pivotal role for the interleukin-17A (IL-17A) cytokine family in human inflammatory or autoimmune diseases and neurodegenerative diseases, including psoriasis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and glaucoma. Studies in recent years have shown that the mechanism of action of IL-17A is more subtle than simply causing inflammation. Although the specific mechanism of IL-17A in neurodegenerative diseases is still controversial, it is generally accepted now that IL-17A causes diseases by activating glial cells. In this review article, we will focus on the function of IL-17A, in particular the proposed roles of IL-17A, in the pathogenesis of neurodegenerative diseases.
32839670 Hydroxychloroquine is protective to the heart, not harmful: a systematic review. 2020 Sep Hydroxychloroquine (HCQ) has been shown to be at least somewhat effective in treating patients with coronavirus disease 2019 (COVID-19). Recently the US Food and Drug Administration and Centers for Disease Control and Prevention warnings of fatal cardiac toxicity from torsades de pointes (TDP) arrhythmia from HCQ receipt have been made, notwithstanding the long safe provision of HCQ to treat lupus and rheumatoid arthritis. This has resulted in restricted access of HCQ for COVID-19 treatment. We hypothesized that HCQ and azithromycin have not been reported to cause significant acute cardiac arrhythmic mortality. We performed a literature search for the effects of HCQ and azithromycin on the heart. No TDP or related deaths were found to have been reported as a result of HCQ and azithromycin receipt in the peer-reviewed literature. On the contrary, HCQ and azithromycin were both found to substantially reduce cardiac mortality and also decrease thrombosis, arrhythmia and cholesterol in treated patients in recent peer-reviewed studies and meeting presentations. HCQ and azithromycin do not cause TDP cardiac mortality; rather, HCQ decreases cardiac events. HCQ should not be restricted in COVID-19 patients out of fear of cardiac mortality.
32474886 Correction to: Sustained improvement in work outcomes in employed patients with rheumatoid 2020 Aug The original version of this article was published without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed.].
32210960 Semaphorins in Angiogenesis and Autoimmune Diseases: Therapeutic Targets? 2020 The axonal guidance molecules, semaphorins, have been described to function both physiologically and pathologically outside of the nervous system. In this review, we focus on the vertebrate semaphorins found in classes 3 through 7 and their roles in vascular development and autoimmune diseases. Recent studies indicate that while some of these vertebrate semaphorins promote angiogenesis, others have an angiostatic function. Since some semaphorins are also expressed by different immune cells and are known to modulate immune responses, they have been implicated in autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. We conclude this review by addressing strategies targeting semaphorins as potential therapeutic agents for angiogenesis and autoimmune diseases.
32002008 Pes anserine syndrome in post knee arthroplasty. A rare case report. 2020 Jan Pes anserine syndrome is a cause of inferomedial knee pain. It occurs in patients with diabetes mellitus, osteoarthritis, rheumatoid arthritis and in overweight patients. It is a challenge to identify the causes of knee pain following knee replacement surgery. We present a case report of pes anserine syndrome in a 79-year-old female who had undergone knee arthroplasty 13 years prior. She was pain free until one year ago when her knee pain resurfaced without any symptoms of infection or history of trauma. She was successfully treated with a combination of stretching exercise and steroid local steroid injection. We want to highlight that such common condition as pes anserine syndrome, could occur in total knee arthroplasty, and should be considered as one of the possible diagnosis.
33049127 Clinical value of soluble ST2 in cardiology. 2020 Oct We are constantly looking for new parameters and markers that can help in the assessment of patients with various diseases, including cardiac disorders; this can translate into better care and improved prognosis. Suppression of tumorigenicity 2 (ST2) has recently gained interest as a potential biomarker in many fields: it is involved in many inflammatory diseases and allergies, including asthma, rheumatoid arthritis and inflammatory bowel disease, and it participates in cardiovascular pathophysiology. Suppression of tumorigenicity 2 is being investigated as a promising biomarker in heart diseases. The interaction of interleukin 33 (IL-33) and ST2L is part of a cardioprotective pathway that prevents fibrosis and inhibits inflammatory response, hypertrophy and apoptosis of cardiomyocytes. In this review, we try to summarize the current knowledge about the usefulness of soluble ST2 (sST2) in cardiology. Clinical data show promising results for the possibility of using sST2 in various diseases, such as arrhythmia, hypertension, myocarditis, acute aortic syndrome, and coronary artery disease (CAD). This novel biomarker may also play a role in heart transplantation and perioperative care.
32436620 Analysis of Immunosuppressant Drugs in Whole Blood by Liquid Chromatography-Tandem Mass Sp 2020 Jun Immunosuppressant medications help suppress the immune system response through inhibition of various checkpoints in the regulatory biochemical pathway. This is useful in prevention of organ rejection in transplantation or in the treatment of autoimmune diseases such as lupus or rheumatoid arthritis. Quantification of immunosuppressive drugs in blood is needed clinically for optimization of treatment and to avoid toxicity or unwanted side effects. Here, we describe a quantitative method to determine the concentration of cyclosprine A, tacrolimus, sirolimus, and everolimus in whole blood. This method has been used for many years clinically to support patient care. © 2020 by John Wiley & Sons, Inc.
32089926 Bilateral Stress Fractures of the Femoral Neck after Total Knee Arthroplasty: Importance o 2020 Unilateral stress fracture of the femoral neck following total knee arthroplasty (TKA) is a rare complication; only 21 cases are described in English literature so far. Bilateral stress fractures of the femoral neck occurring simultaneously following a bilateral TKA have been seen in only 2 cases till now. We report a patient suffering from rheumatoid arthritis of both knees, who was treated with bilateral TKA. She developed spontaneous fractures of the femoral neck on both sides 12 months following the TKA. She was treated with bilateral total hip arthroplasty (THA). Stress fracture of the femoral neck should be suspected in patients complaining of hip pain who have undergone TKA.
32911791 Multicentric Reticulohistiocytosis Exhibiting Positive HLA-B*07 and HLA-B*08: A Case Repor 2020 Sep 8 Multicentric reticulohistiocytosis (MRH) is a rare cause of destructive inflammatory arthritis involving both small, as well as larger joints. We report the case of a 40-year-old Caucasian female with a family history of neoplasia who was referred to our service witha two-month history of inflammatory joint pain. On examination, the patient had inflammatory arthritis, mainly involving the peripheral joints, sacroiliac joint pain, and numerous papulonodular mucocutaneous lesions, including periungual "coral beads". Imaging tests revealed erosive arthritis with synovitis and tenosynovitis, sacroiliac joint changes, as well as papulonodular mucosal lesions in the nasal vestibule, the oropharyngeal mucosa, and supraglottic larynx. She tested positive for HLA-B*07 (Human Leukocyte Antigen B*07) and HLA-B*08, ANA (antinuclear antibodies), RF (rheumatoid factor), anti-Ro52, anti-SSA/Ro, and anti-SSB/La antibodies. The skin biopsy was suggestive of MRH, showing a histiocyte infiltrate and frequent giant multinucleated cells. The patient exhibited favorable outcomes under Methotrexate, then Leflunomide. However, she displayed worsening clinical symptoms while under Azathioprine. To our knowledge, this is the first case of MRH to exhibit positive HLA-B*07 together with HLA-B*08. The rarity of MRH, its unknown etiology and polymorphic clinical presentation, as well as its potential neoplastic/paraneoplastic, and autoimmune nature demand extensive investigation.
33300400 Association between inflammasome-related polymorphisms and psoriatic arthritis. 2021 May Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1β-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes.Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329).Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05-1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02-1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23-2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13-2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04-2.55), p = 0.030].Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA.
32575162 Characterization of antiapoptotic microRNAs in primary Sjögren's syndrome. 2020 Dec During the development of primary Sjögren's syndrome (pSS), aberrant expression of autoantigen is a hallmark event. To explore the regulation of autoantigen tripartite motif containing 21 (Ro/SSA, TRIM21), microRNA profiling was performed in our previous study. In which, two TRIM21-targeting microRNAs were identified, namely miR-1207-5p and miR-4695-3p. To further pursue their roles in the development of pSS, assays were performed with cultured human submandibular gland (HSG) cells, and salivary gland tissues. Results showed that transfection of miR-1207-5p or miR-4695-3p mimics down-regulated not only the expression of TRIM21, but also the levels of pro-apoptotic genes B cell lymphoma 2 associated X (BAX), Caspase 9 (CASP-9) and Caspase 8 (CASP-8). This finally led to antiapoptotic phenotypes in HSG cells. Consistent with the antiapoptotic activity, transfection of microRNA inhibitors up-regulated the expression of TRIM21 and led to a pro-apoptotic phenotype. These therefore propose miR-1207-5p and miR-4695-3p as two antiapoptotic microRNAs functioning through apoptosis pathway. Supporting this speculation, assays performed with salivary gland tissues revealed down-regulation of miR-1207-5p and miR-4695-3p, as well as up-regulation of TRIM21 and pro-apoptotic CASP-8 gene in pSS samples. SIGNIFICANCE OF THE STUDY: For pSS patients, apoptosis of acinar and ductal epithelial cells has been proposed to be a potential mechanism that impairs the secretion of salivary glands. In our study, two autoantigen-targeting microRNAs were characterized as antiapoptotic microRNAs functioning through apoptosis pathway, which may be potential targets for the treatment of pSS.
32960015 Pseudoaneurysm of the Posterior Humeral Circumflex Artery After Reverse Shoulder Arthropla 2020 Jul CASE: A 78-year-old woman with rheumatoid arthritis and a massive rotator cuff tear of the right shoulder was treated with reverse shoulder arthroplasty, but a pseudoaneurysm in the posterior humeral circumflex artery suddenly ruptured 7 months after surgery. Embolization of the pseudoaneurysm and skin treatment successfully relieved her symptoms without implant removal. CONCLUSION: Although a rare occurrence, vascular complication can occur after shoulder arthroplasty. The cause of the pseudoaneurysm was hypothesized to be repetitive contact between the humeral component and the artery and/or chronic traction of the blood vessel because of its chronic onset.
32614469 Neutrophil-targeted engineered prodrug nanoparticles for anti-inflammation. 2020 Aug Inflammation response is a defense to infection induced by invading pathogen or tissue injury. However, exaggerated inflammation may cause autoimmune or inflammatory disorders, such as acute respiratory distress syndrome, sepsis, stroke and rheumatoid arthritis. Anti-inflammatory agents and anti-cytokine therapy have been developed to inhibit inflammation pathways and neutralize cytokine storm, but the off-targeting delivery and damage in immune system cause systemic severe side-effect. Selective targeting, precise intracellular drug delivery and induced programed apoptosis of neutrophils may be a potential strategy to regulate the inflammatory responses for immune homeostasis. In this commentary, we summarized that the assembled engineering prodrug nanoparticles carrying doxorubicin via pH-responsive bonds that specifically target to and efficiently induce the apoptosis of activated neutrophils for anti-inflammation with high therapeutic efficacy and no systemically toxicity could be a promising strategy for neutrophil-mediated diseases.
32475188 Which is the best SLE activity index for clinical trials? 2021 Jan Following the advent of molecular targeted drugs, a paradigm shift in treatment similar to that in rheumatoid arthritis has been expected in the treatment of systemic lupus erythematosus (SLE), but clinical trials for drugs that many specialists believed to be effective have failed repeatedly. The causes are not simple, but include the heterogeneity of SLE, inclusion criteria, lack of appropriate disease activity measures, and relapse criteria. This review outlines the disease activity indices used in SLE, discusses their advantages and disadvantages, and describes the ideal activity index.
32258416 Streptococcus Pneumoniae-associated Thrombotic Microangiopathy in an Immunosuppressed Adul 2020 A 62-year-old male who was receiving prednisolone and methotrexate for scleroderma and rheumatoid arthritis complained of diarrhea and vomiting, and was transferred to our hospital for detailed examination and treatment of renal dysfunction and thrombocytopenia. Hemolytic anemia and crushed erythrocytes were found during the patient's course; therefore, we suspected thrombotic microangiopathy (TMA). His ADAMTS13 activity was 60.3% and his ADAMTS13 inhibitor was under 0.5. In addition, his blood culture was positive for Streptococcus pneumoniae, and we finally diagnosed Streptococcus pneumoniae-associated TMA (pTMA). The patient was treated with antibiotics and hemodialysis. The patient recovered and was discharged on the 45(th) hospital day. Adult pTMA cases are remarkably rare. We herein report a successfully treated adult case of pTMA.
32076129 Views on glucocorticoid therapy in rheumatology: the age of convergence. 2020 Apr After decades of sometimes fierce debate about the advantages and disadvantages of glucocorticoids, an age of convergence has been reached. Current recommendations for the management of diseases such as rheumatoid arthritis (RA), polymyalgia rheumatica and large vessel vasculitis reflect the current consensus that as much glucocorticoid as necessary, but as little as possible, should be used. Over the past few years, a range of glucocorticoid-sparing strategies have been developed, as have tools to improve the management of this therapy. A comprehensive view of glucocorticoid-induced osteoporosis has also emerged that recognizes that bone fragility is not solely determined by the dose and duration of glucocorticoid treatment. Nevertheless, open questions remain around whether long-term use of very low doses of glucocorticoids is a realistic option for patients with RA and whether the search for innovative glucocorticoids or glucocorticoid receptor ligands with improved benefit-to-risk ratios will ultimately be successful.