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ID PMID Title PublicationDate abstract
30375409 Interplay between sympathetic nervous system and inflammation in aseptic loosening of hip 2018 Oct 30 Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL. Our results showed that periprosthetic inflammation does not trigger a systemic response of the sympathetic nervous system, but is mirrored rather by the impairment of the sympathetic activity locally in the hip joint. Moreover, macrophages were identified as key players in the local regulation of inflammation by the sympathetic nervous system in a process that is implant debris-dependent and entails the reduction of both adrenergic and Neuropetide Y (NPY)-ergic activity. Additionally, our results showed a downregulation of semaphorin 3A (SEMA3A) that may be part of the mechanism sustaining the periprosthetic inflammation. Overall, the local sympathetic nervous system emerges as a putative target to mitigate the inflammatory response to debris release and extending the lifespan of orthopedic implants.
29460700 The lupus patient with positive rheumatoid factor. 2018 Jul Background Patients with systemic lupus erythematosus (SLE) may form clusters with clinical manifestations and autoantibodies. Objective The objective of this report is to study whether SLE patients with positive rheumatoid factor (RF) have a special clinical and/or serological profile. Methods A retrospective study of 467 SLE patients seen at a single rheumatology unit was conducted. Epidemiological data (age, gender, age at disease onset, ethnic background and tobacco use), clinical data (malar rash, photosensitivity, oral ulcers, discoid lesions, serositis, glomerulonephritis, convulsions, psychosis, hemolytic anemia, leukopenia, lymphocytopenia, arthritis and hypothyroidism) and serological profile (anti-dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-RNP, anti-Sm, IgG aCL, IgM aCL, lupus anticoagulant, direct Coombs and RF) were collected. Patients with positive and negative RF were compared. Results RF was found in 24.9% of the sample. In univariate analysis, RF was positively associated with butterfly rash ( p = 0.04), anti-Ro ( p = 0.03), anti-Sm antibodies ( p = 0.01) and hypothyroidism ( p = 0.01) and negatively associated with glomerulonephritis ( p = 0.003). Logistic regression showed that only glomerulonephritis ( p = 0.03; OR = 0.45; 95% CI = 0.21-0.93) and anti-Ro ( p = 0.009; OR = 2.3; 95% CI = 1.24-4.57) were independent associations. Conclusion In our sample RF was associated with protection from glomerulonephritis and with higher prevalence of anti-Ro antibodies.
29380927 Increased hyperpolarized [1-(13) C] lactate production in a model of joint inflammation is 2018 Apr Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)-induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1-(13) C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate-to-pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the (13) CO(2) /H(13) CO(3)(-) ratio, in animals injected with hyperpolarized H(13) CO(3)(-) , to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA-induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid-sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA-induced inflammation.
29668614 Arthritis of large joints shown as a rare clinical feature of cytokine release syndrome af 2018 Apr RATIONALE: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of therapy that is being used in an increasing number of patients with acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is the most common complication following CAR-T treatment, but the current understanding of the clinical manifestations and pathogenesis of CRS is still limited. PATIENT CONCERNS: A 34-year-old male patient was diagnosed with ALL in June 2015. Complete remission (CR) was achieved after induction chemotherapy. The patient received 8 cycles of consolidation chemotherapy to maintain CR. In May 2017, the patient had recurrent ALL. Induction chemotherapy was given again, but without remission. In October 2017, CAR-T cell therapy was given. On October 14, the patient was pretreated with an FC regimen (fludarabine phosphate 50 mg qd on days 1-3; cyclophosphamide 0.4 g qd on days 1-3). CAR-T cells were infused on October 19 and October 20, with the number of infused cells at 2 × 10/kg and 1 × 10/kg, respectively. On October 25, the patient had a high fever, swelling, and pain in the large joints of the limbs, and joint effusion. DIAGNOSIS: This patient was diagnosed with relapsed ALL, and he developed CRS after CAR-T therapy. INTERVENTIONS: Tacilizumab (400 mg) was infused after CRS was diagnosed, and another dose of tacilizumab (240 mg) was given 6 days later. The pain was also treated with an analgesic drug. Methylprednisolone (1 mg/kg) was given to treat arthritis of the large joints. OUTCOMES: The patient's temperature was back to normal within 1 hour following the treatment of tacilizumab, but the pain in the large joints was progressively aggravated. The joint swelling and pain were obviously alleviated after the treatment of methylprednisolone, and the joint mobility was gradually recovered. LESSONS: CRS after CAR-T therapy can manifest as a high fever with swelling and pain in the large joints of the limbs, similar to rheumatoid arthritis. Tocilizumab can lower the body temperature, but it has no significant effect on arthritis. Glucocorticoids can rapidly alleviate joint swelling and pain.
30320936 The role of IL-3 in bone. 2018 Oct 15 In the recent past, there has been a burgeoning interest in targeting cytokines such as IL-3 for specific disease conditions of bone such as rheumatoid arthritis and multiple myeloma. Unlike other cytokines, IL-3 is a cytokine with a multilineage potential and broad spectrum of target cells and it plays a vital role in hematopoiesis. Due to its common receptor subunit, the action of IL-3 shows functional redundancy with other cytokines such as the granulocyte-macrophage colony-stimulating factor and IL-5. IL-3 has been successfully used in ameliorating radiation-induced bone marrow aplasia and similar conditions. However, the role of IL-3 in bone cells has not been fully unraveled yet; therefore, the aim of this overview is to present the effects of IL-3 in bone with a special emphasis on osteoclasts and osteoblasts in a concise manner.
30274628 Thrombotic Microangiopathies with Rheumatologic Involvement. 2018 Nov Thrombotic microangiopathies are heterogeneous disorders characterized by microangiopathic hemolytic anemia with thrombocytopenia and renal injury. There are a variety of causes, including metabolic disorders, infections, medications, complement disorders, pregnancy, malignancy, and autoimmune disorders. This review focuses on renal thrombotic microangiopathy in the setting of rheumatologic diseases. Systemic lupus erythematosus is the most common autoimmune disease associated with thrombotic microangiopathy. Other etiologies include scleroderma renal crisis and antiphospholipid antibody syndrome, which can be primary or secondary to autoimmune diseases including systemic lupus erythematosus. There have also been case reports of thrombotic microangiopathy in the setting of rheumatoid arthritis and dermatomyositis.
30244458 Generation of Specific Aptamers. 2018 Nucleic acid aptamers are therapeutic agents consisting of short single-strand DNA or RNA oligonucleotides, which have the ability to bind to target therapeutic molecules with high affinity and specificity, and have been developed as potent drugs for the treatment of rheumatoid arthritis. Aptamers have unique and advantageous features over antibodies, such as superior affinity with nano- or pico-molar dissociation constants, and ease of chemical synthesis, modification, and inactivation by designing antisense sequences. In this chapter, using a DNA-oligonucleotide pool, the technology of proteoliposome-systematic evolution of ligands by exponential enrichment (SELEX) is introduced. By using this technique, potential therapeutic agents with high affinity and specificity could be obtained.
30181915 Damage-Associated Molecular Patterns in Inflammatory Diseases. 2018 Aug Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). Although DAMPs contribute to the host's defense, they promote pathological inflammatory responses. Recent studies have suggested that various DAMPs, such as high-mobility group box 1 (HMGB1), S100 proteins, and heat shock proteins (HSPs), are increased and considered to have a pathogenic role in inflammatory diseases. Here, we review current research on the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. We also discuss the possibility of DAMPs as biomarkers and therapeutic targets for these diseases.
30008749 A Rapidly Fatal Case of Low-Dose Methotrexate Toxicity. 2018 An 82-year-old female presented with multiple oral ulcers and malena for 1 week. Her laboratory tests revealed pancytopenia and acute renal failure. She had history of rheumatoid arthritis for which she was taking 7.5 mg methotrexate weekly and stage 4 chronic kidney disease from diabetic nephropathy. During the hospital stay, she developed pneumonia and septic shock requiring norepinephrine and vasopressin. She underwent continuous venovenous hemodiafiltration. Leucovorin, filgrastim, and multiple packed red blood cell and platelet transfusions were given. She remained hypotensive and pancytopenic despite all interventions. She died on day 6 of hospital stay from acute hypoxic respiratory failure due to septic shock.
29574435 Autoimmune pancreatitis with concomitant autoimmune haemolytic anaemia. 2018 Mar 23 Autoimmune pancreatitis (AIP) is an infrequent cause of acute pancreatitis, being more commonly associated with chronic pancreatitis. AIP can be associated with other autoimmune manifestations, including Sjögren's, inflammatory bowel disease, primary biliary cirrhosis, rheumatoid arthritis, hypothyroidism and sarcoidosis. Rarely, concurrent autoimmune haemolytic anaemia (AIHA) is observed, as seen in our case report of a 33-year-old postpartum woman.
29389238 Inflammatory Diseases of the Gut. 2018 Feb Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract whose prevalence has been dramatically increasing over the past decade. New studies have shown that IBD is the second most common chronic inflammatory disease worldwide after rheumatoid arthritis, affecting millions of people mainly in industrialized countries. Symptoms of IBD include frequent bloody diarrhea, abdominal cramping, anorexia, abdominal distension, and emesis. Although the exact etiology is unknown, it has been postulated that immunological, microbial, environmental, nutritional, and genetic factors contribute to the pathogenesis and severity of IBD. Today, no treatment has consistently been shown to be successful in treating IBD. This review summarizes current research on the epidemiology, etiology, pathophysiology, and existing treatment approaches, including pharmaceutical and nutritional options for IBD.
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.
29480591 Atherosclerotic vascular disease in the autoimmune rheumatologic woman. 2018 Feb Autoimmune rheumatologic conditions have increased cardiovascular morbidity and mortality compared to the general population. Many of these diseases occur more commonly in women, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis, and Sjogren's. Most of the literature that has identified the link between autoimmune diseases and atherosclerotic cardiovascular disease (ASCVD) has been regarding patients with RA and SLE. The reason for the increased ASCVD is related to both traditional risk factors for atherosclerosis and nontraditional risk factors such as the burden of inflammation. Presently, our ability to adequately determinecardiovascular risk in the autoimmune patient is subpar, as scoring systems fail to take into account the role of inflammation. No present guidelines exist that take into account the increased burden of cardiovascular disease in this complex patient cohort.
29666259 Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environ 2018 May 1 The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo. Intriguingly, the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the xenobiotic effects of many pollutants, including tobacco combustion products, has been found to activate similar biologic effects. Prompted by these similarities, we sought to determine whether the SE and AhR signaling pathways interact in autoimmune arthritis. Here we uncovered a nuclear factor kappa B-mediated synergistic interaction between the SE and AhR pathways that leads to markedly enhanced osteoclast differentiation and Th17 polarization in vitro. Administration of AhR pathway agonists to transgenic mice carrying human SE-coding alleles resulted in a robust increase in arthritis severity, bone destruction, overabundance of osteoclasts, and IL17-expressing cells in the inflamed joints and draining lymph nodes of arthritic mice. Thus, this study identifies a previously unrecognized mechanism of gene-environment interaction that could provide insights into the well-described but poorly understood amplification of the genetic risk for RA upon exposure to environmental pollutants.
30150979 IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Prim 2018 OBJECTIVE: To investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren's syndrome (pSS) patients. METHODS: This study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation. RESULTS: We found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4(+) T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3. CONCLUSION: Our findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS.
29977933 Expression of Gαq Is Decreased in Lymphocytes from Primary Sjögren's Syndrome Patients a 2018 Primary Sjögren's syndrome (pSS) is a rheumatic disease characterized by the destruction of salivary and lacrimal glands, and its pathogenesis mechanism remains unclear. Gαq is the α-subunit of the heterotrimeric Gq protein. Researches demonstrated that Gαq was involved in the pathogenesis regulation of several rheumatic diseases. This study explored the role of Gαq in pSS. Gαq mRNA levels in peripheral blood mononuclear cells (PBMCs) from 39 patients and 26 healthy controls (HCs) were investigated using real-time PCR. IL-17A serum concentrations in 22 pSS patients and 23 HCs were tested by ELISA, and the clinical significance of Gαq was analyzed. The association of Gαq with interleukin-17A (IL-17A) expression was also analyzed in patients with pSS. We showed that Gαq expression in PBMCs from patients with pSS was significantly lower than that in PBMCs from HCs. Gαq expression level was closely associated with pSS disease activity. Furthermore, a negative association was also found in IL-17A and Gαq expression level. These data suggest that Gαq is involved in pSS pathogenesis regulation, possibly due to its regulation of Th17. These results provide new insights into the pSS pathogenesis mechanism involving abnormal Th17 regulation.
27930436 SELF-PEELING EPIRETINAL MEMBRANE. 2018 Summer PURPOSE: To present a self-peeling epiretinal membrane (ERM) in a patient with spontaneously improved retinal capillary hemangioma in the left eye. METHODS: The authors demonstrate the improvement of an untreated retinal capillary hemangioma and resolution of ERM with fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Genetic testing excluded von Hippel-Lindau disease in this patient. RESULTS: Evaluation of a patient with rheumatoid arthritis revealed retinal capillary hemangioma with retinal exudates at the temporal peripheral fundus and an ERM in the left eye. Patient was asymptomatic and elected observation. Three years after the initial examination, visual acuity and macular appearance improved after spontaneous resolution of the ERM. Capillary hemangioma was smaller and retinal exudates resolved without treatment. CONCLUSION: This case report demonstrates a self-peeling ERM associated with a retinal capillary hemangioma. This case contributes the literature describing the natural history of ERMs associated with peripherally located capillary hemangiomas in patients without von Hippel-Lindau disease.
30317071 Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical 2019 Jan BACKGROUND: Multiple sclerosis (MS) afflicts more than 2.5 million individuals worldwide and this number is increasing over time. Within the past years, a great number of disease-modifying treatments have emerged; however, efficacious treatments and a cure for MS await discovery. Thymosins, soluble hormone-like peptides produced by the thymus gland, can mediate immune and non-immune physiological processes and have gained interest in recent years as therapeutics in inflammatory and autoimmune diseases. METHODS: Pubmed was searched with no time constraints for articles using a combination of the keywords "thymosin/s" or "thymus factor/s" AND "multiple sclerosis", mesh terms with no language restriction. RESULTS: Here, we review the state-of-the-art on the effects of thymosins on MS and its experimental models. In particular, we describe what is known in this field on the roles of thymosin-α1 (Tα1) and -β4 (Tβ4) as potential anti-inflammatory as well as neuroprotective and remyelinating molecules and their mechanisms of action. CONCLUSION: Based on the data that Tα1 and Tβ4 act as anti-inflammatory molecules and as inducers of myelin repair and neuronal protection, respectively, a possible therapeutic application in MS for Tα1 and Tβ4 alone or combined with other approved drugs may be envisaged. This approach is reasonable in light of the current clinical usage of Tα1 and data demonstrating the safety, tolerability and efficacy of Tβ4 in clinical practice.
29478005 Pleuroparenchymal fibroelastosis with positive MPO-ANCA diagnosed with a CT-guided percuta 2018 Feb 24 A 67-year-old woman was referred to our hospital because of gradually increasing dyspnoea on exertion for 6 months. Chest CT scan showed subpleural parenchymal fibrotic opacities with traction bronchiectasis in the bilateral upper lung fields. Serum rheumatoid factor and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were positive. There was no evident reason to suspect connective tissue disease such as ANCA-associated vasculitis or rheumatoid arthritis. We performed a CT-guided percutaneous needle biopsy of the subpleural lesion that showed slight uptake on the fluorodeoxyglucose-positron emission tomography (FDG-PET) CT scan. This specimen showed subpleural fibrosis as evidenced by an abnormal increase of elastic tissue and minimal collagen deposition, which indicated pleuroparenchymal fibroelastosis (PPFE). Although PPFE can be associated with a variety of causes, its association with MPO-ANCA is unknown. A CT-guided transthoracic lung biopsy caused no adverse events and was useful in the diagnosis of PPFE in our patient.
28592200 Anti-carbamylated protein antibodies in systemic lupus erythematosus patients with articul 2018 Jan Objective Several studies have evaluated the prevalence of rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA) in systemic lupus erythematosus (SLE) patients but no data are available on the anti-carbamylated proteins (anti-CarP), a new biomarker for rheumatoid arthritis (RA). We evaluated the anti-CarP prevalence in SLE patients with joint involvement and the associations with different phenotypes. Methods Seventy-eight SLE patients with joint involvement were enrolled (F/M 73/5; mean ± SD age 47.6 ± 11.2 years; mean ± SD disease duration 214.3 ± 115.6 months). As control groups, we evaluated SLE patients without joint manifestations ( N = 15), RA ( N = 78) and healthy individuals (HS, N = 98). Anti-CarP were assessed by home-made ELISA in all patients and controls, RF and ACPA in SLE patients with joint involvement (commercial ELISA kit). Results The prevalence of anti-CarP in SLE patients with joint involvement was similar to RA ( p = NS) and significantly higher compared with SLE without joint involvement and HS ( p < 0.0001, p < 0.0001, respectively). Four patients were positive for all three antibodies: seventy-five percent of these showed Jaccoud arthropathy. Fourty-five percent of ACPA-ve/RF-ve patients were anti-CarP + ve. Conclusions The evaluation of anti-CarP in SLE joint involvement demonstrated a prevalence of almost 50%, similar to RA and significantly higher than SLE without joint involvement and HS.