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ID PMID Title PublicationDate abstract
32341782 Living with a chronic disease: A quantitative study of the views of patients with a chroni 2020 OBJECTIVES: Chronic diseases have an impact on and change patient's lives which means that they need to find ways to cope with the new situation. The aim was to describe how the chronic disease has influenced patients' views of their life situation. METHODS: The study was quantitative in design with data collected using a semi-structured questionnaire. Descriptive statistics were used to compare similarities and differences between patients with asthma-allergy, diabetes mellitus, cancer and inflammatory rheumatoid arthritis. RESULTS: Changes in their life were experienced as a negative outcome for the majority of participants. Support can be in the form of interpersonal support from various persons, but also from activities and beliefs/religion. Family and friends as well as healthcare professionals were identified as being most supportive. Sadness and worry were the most common emotions among the participants and their surrounding networks. CONCLUSION: People with a chronic disease have to live with the consequences the disease has for their life situation. They need to find strategies to cope with the negative outcome in their new life. Support from their own network and healthcare professionals can be helpful in the new life situation.
32610879 Hydroxychloroquine for COVID-19: What is our Current State of Knowledge? 2020 Jun Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.
32400033 Intralymphatic histiocytosis in healing cellulitis: Case report and review of the literatu 2020 Oct Intralymphatic histiocytosis (ILH) is a rare skin benign condition observed in a variety of inflammatory settings. It is characterized by the presence of ectatic dermal lymphatic vessels containing aggregates of histiocytes. Associated conditions that have been identified include rheumatoid arthritis, metallic orthopedic implants, inflammatory bowel disease, and malignancies of the breast, skin, and colon. Some cases with no attributable underlying cause have been described. The pathophysiology of ILH is not well understood. It has been proposed that it may represent macrophage migration during immune activation. Herein, we present the first description of ILH observed in the healing phase of cellulitis on the skin of the breast. Awareness of this possibility is important when the diagnosis of intravascular carcinomatosis is being considered.
32292559 Synthesis and Evaluation of Noncovalent Naphthalene-Based KEAP1-NRF2 Inhibitors. 2020 Apr 9 The oxidative stress response, gated by the protein-protein interaction of KEAP1 and NRF2, has garnered significant interest in the past decade. Misregulation in this pathway has been implicated in disease states such as multiple sclerosis, rheumatoid arthritis, and diabetic chronic wounds. Many of the known activators of NRF2 are electrophilic in nature and may operate through several biological pathways rather than solely through the activation of the oxidative stress response. Recently, our lab has reported a nonelectrophilic, monoacidic, naphthalene-based NRF2 activator which exhibited good potency in vitro. Herein, we report a detailed structure-activity relationship of naphthalene-based NRF2 activators, an X-ray crystal structure of our monoacidic KEAP1 inhibitor, and identification of an underexplored area of the NRF2 binding pocket of KEAP1.
32276504 Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Respons 2020 Apr 8 Following fifteen years of research, neutrophil extracellular traps (NETs) are widely reported in a large range of inflammatory infectious and non-infectious diseases. Cumulating evidences from in vitro, in vivo and clinical diagnostics suggest that NETs may play a crucial role in inflammation and autoimmunity in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Most likely, NETs contribute to breaking self-tolerance in autoimmune diseases in several ways. During this review, we discuss the current knowledge on how NETs could drive autoimmune responses. NETs can break self-tolerance by being a source of autoantigens for autoantibodies found in autoimmune diseases, such as anti-citrullinated protein antibodies (ACPAs) in RA, anti-dsDNA in SLE and anti-myeloperoxidase and anti-protein 3 in AAV. Moreover, NET components could accelerate the inflammatory response by mediating complement activation, acting as danger-associated molecular patterns (DAMPs) and inflammasome activators, for example. NETs also can activate other immune cells, such as B cells, antigen-presenting cells and T cells. Additionally, impaired clearance of NETs in autoimmune diseases prolongs the presence of active NETs and their components and, in this way, accelerate immune responses. NETs have not only been implicated as drivers of inflammation, but also are linked to resolution of inflammation. Therefore, NETs may be central regulators of inflammation and autoimmunity, serve as biomarkers, as well as promising targets for future therapeutics of inflammatory autoimmune diseases.
32049468 Vitamin D in autoimmune bullous disease. 2020 Feb 12 Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic lupus erythematosus. More recently, such a link has been also proposed for autoimmune bullous diseases (AIBD). This is a relatively rare and potentially life-threatening, organ-specific group of inflammatory skin diseases characterized by the presence of tissue-bound and circulating autoantibodies against various molecules present in desmosomes (in pemphigus diseases) or hemidesmosomes (in pemphigoid diseases). In addition to the well-known role of vitamin D in calcium and phosphate homeostasis, the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol), exerts potent effects on cellular differentiation and regulation of immune responses via binding to the vitamin D receptor present in most cells of the immune system. Since cells of both, the innate and adaptive immune systems, are known to be relevant in AIBD, the role of vitamin D analogues in the treatment of patients with these disorders deserves much attention. This mini-review summarizes recent epidemiological and experimental studies on vitamin D involvement in the autoimmune bullous diseases.
31825400 A novel colorimetric and far-red emission ratiometric fluorescent probe for the highly sel 2020 Feb 3 Hypochlorous acid (HOCl)/hypochlorite (OCl-), an important reactive oxygen species, plays a number of important roles in various physiological processes. However, abnormal levels of OCl- can cause many serious diseases, such as atherosclerosis, rheumatoid arthritis, cardiovascular disease, and cancer. The development of efficient methods to monitor OCl- in biological systems is therefore of particular importance. Thus, we herein report a novel isophorone-based fluorescent probe, i.e., DCOH-FR-OCl, for OCl- detection. This probe was found to exhibit colorimetric and far-red ratiometric fluorescence response signals, excellent selectivity and sensitivity for OCl- (detection limit, 88.06 nM), a remarkably large Stokes shift (158 nm), an ultrafast response (completed within 3 s), perfect photostability, and good water solubility (100% in aqueous media). DCOH-FR-OCl, as we know, is the first probe that can detect OCl- by using two different response signals at an ultrafast speed with a large Stokes shift in fully aqueous media. Furthermore, DCOH-FR-OCl can be successfully employed in the real-time imaging of endogenous and exogenous OCl- in living cells.
31352871 Menopausal symptoms and related factors among Cambodian women. 2020 Apr This study analyzed the prevalence and severity of menopausal symptoms and associated factors among Cambodian women. A cross-sectional study was performed with 200 women aged 40-60 years in three provinces and one urban area in Cambodia from July 2017 to August 2017. Three symptom categories: somatic, psychological, and urogenital symptoms (totaling 11 symptoms) related to menopause were assessed using the Khmer version of Menopause Rating Scale (MRS). Over one-fifth (21.5%) of the participants were premenopausal; 22.5% were perimenopausal, and 56% were postmenopausal. Somatic and psychological symptoms occurred more frequently than urogenital symptoms in all three statuses. The three most prevalent symptoms for all women were physical and mental exhaustion (88.1%), irritability (85.9%), and sleep problems (82.5%). The average MRS score was 12.22 ± 5.37 (range 0-44). Postmenopausal women had significantly higher rates of menopausal symptoms than pre- and perimenopausal women. Increased severity of menopausal symptoms was associated with less personal income (≤100 US$), higher parity (>4 children), abortion(s), use of calcium supplements, and history of heart disease and rheumatoid arthritis. This study demonstrated a high prevalence of menopausal symptoms among Cambodian women in Cambodia. A multidisciplinary approach is needed to deal with independent factors associated with these symptoms.
32395171 Acute Inflammatory Optic Neuritis Associated with a Self-Taper of Oral Prednisone in a Pat 2020 Jun Therapies, such as adalimumab, aimed at inhibiting the pro-inflammatory cytokine "tumour necrosis factor" (TNF) are effective and are frequently used in combination with non-biologic disease-modifying anti-rheumatic drugs to treat rheumatoid arthritis (RA) and other autoimmune diseases. Some reports indicate that, rarely, demyelinating CNS disorders such as optic neuritis can present in association with therapy initiation, whilst others suggest that there is no association between the two. Oral corticosteroids such as prednisone, though similarly effective in the treatment of inflammatory or auto-immune conditions, can be associated with adverse effects upon their discontinuation or tapering. We present a patient who developed an acute inflammatory optic neuropathy shortly after a self-taper of oral prednisone while being treated with adalimumab for RA, and discuss the challenge of deciding whether or not to halt anti-TNF therapy.
33019843 Refracture after plate removal following ulnar shortening osteotomy for ulnar impaction sy 2021 Feb Level III, case-control study.
32557263 Type I Interferons in the Pathogenesis and Treatment of Autoimmune Diseases. 2020 Oct Type I interferons (IFN-Is) are a very important group of cytokines that are produced by innate immune cells but also act on adaptive immune cells. IFN-Is possess antiviral, antitumor, and anti-proliferative effects, as well are associated with the initiation and maintenance of autoimmune disorders. Studies have shown that aberrantly expressed IFN-Is and/or type I IFN-inducible gene signatures in the serum or tissues of patients with autoimmune disorders are linked to their pathogenesis, clinical manifestations, and disease activity. Type I interferonopathies with mutations in genes impacting the type I IFN signaling pathway have shown symptoms and characteristics similar to those of systemic lupus erythematosus (SLE). Furthermore, both interventions in animal models and clinical trials of therapies targeting the type I IFN signaling pathway have shown efficacy in the treatment of autoimmune diseases. Our review aims to summarize the functions and targeted therapies (as well as clinical trials) of IFN-Is in both adult and pediatric autoimmune diseases, such as SLE, pediatric SLE (pSLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), Sjögren syndrome (SjS), and systemic sclerosis (SSc), discussing the potential abnormal regulation of transcription factors and epigenetic modifications and providing a potential mechanism for pathogenesis and therapeutic strategies for future clinical use.
33133246 The switch from etanercept originator to SB4: data from a real-life experience on tolerabi 2020 AIMS: Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region. METHODS: Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up. RESULTS: A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7-15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months. CONCLUSION: Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.
32896250 Relationship between common carotid distensibility/aortic stiffness and cardiac left ventr 2021 Mar OBJECTIVES: Chronic inflammatory arthritis (CIAs), including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are characterised by high cardiovascular disease (CVD) risk, partly due to endothelial dysfunction and increased arterial stiffness of the carotid artery and aorta. The aim of the present study is to determine whether ultrasonography measures of carotid and aortic stiffness are correlated with left ventricular mass and function in patients affected by CIAs. METHODS: In this cross-sectional study, we consecutively enrolled outpatients diagnosed with CIAs with no overt CVD. For each participant we assessed disease characteristics, CVD risk factors, medications, including disease-modifying anti-rheumatic drugs (DMARDs), blood pressure, lipids and glucose levels. Carotid ultrasonography was performed in all patients using carotid distensibility (CD) and aortic stiffness index (AoSI) as measures of arterial stiffness. Participants underwent the same day a full echocardiographic study including assessment of left ventricular function and mass (LVM). RESULTS: The study population comprised 208 CIAs patients (mean age 57.4±11.4 y; females 63.9%), including 137 (65.9%) RA, 42 (20.2%) PsA and 29 (13.9%) AS patients. In multiple regression analysis, CD correlated with age (β=-0.198, p<0.0001), mean arterial pressure (β=-0.281, p<0.0001) and treatment with DMARDs (β=-1.976, p=0.021), while AoSI was not associated with any anthropometric, haemodynamic or clinical covariates. CD was inversely related to LVM (r=-0.20, p=0.005), whereas AoSI was directly correlated with diastolic function of the left ventricle (E/E'; r=0.191, p=0.007). CONCLUSIONS: Our results underline the strict correlation between arterial stiffness and left ventricular mass and function in patients with CIAs.
32788921 Use of biologic agents and risk of tuberculosis in Brazil, a tuberculosis high-burden coun 2020 BACKGROUND: Brazil is a country with a high burden of tuberculosis (TB). The immunomodulatory effect of biological therapies is associated with an increased risk of infection. This study evaluated the frequency of TB infection in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis (PsA) after the use of biologic agents in a single center of rheumatology. METHODS: In this observational study, 161 consecutive adult patients with RA, JIA, AS, and PsA using biological therapy were followed up during 55 months to evaluate the occurrence of TB infection throughout treatment. All patients were screened for latent TB infection (LTBI), and TB disease was excluded before introduction of biological therapy. Patients with LTBI received prophylaxis with isoniazid before the start of biological treatment. RESULTS: Of 161 patients on biologics, 31 (19.25%) had positive tuberculin skin test (TST) and received LTBI treatment. Eleven (6.8%) cases of TB were detected in patients on biologics, six (54.5%) had AS, one had PsA (9.09%), two had RA (18.18%), and two had JIA (18.18%). Regarding the use of different biologics, six (54.5%) patients received adalimumab, three (27.2%) infliximab, one (9.09%) etanercept, and one (9.09%) tocilizumab. CONCLUSION: In this study, the frequency of TB infection among 161 patients on biologics, during 55 months of follow-up, was 6.8%. Compared with the national registry of patients receiving biologics (BiobadaBrasil - January 01, 2009 to May 31, 2013), a higher incidence of TB (6.8 versus 0.44%) was found in this sample of patients receiving biological therapy. This study highlights that in a country with high TB burden, the possibility of TB infection in a patient receiving biological therapy should always be considered, even after prophylaxis with isoniazid.
32662821 Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondy 2020 Oct 5 TNF plays a key role in immune-mediated inflammatory diseases including rheumatoid arthritis (RA) and spondyloarthritis (SpA). It remains incompletely understood how TNF can lead to different disease phenotypes such as destructive peripheral polysynovitis in RA versus axial and peripheral osteoproliferative inflammation in SpA. We observed a marked increase of transmembrane (tm) versus soluble (s) TNF in SpA versus RA together with a decrease in the enzymatic activity of ADAM17. In contrast with the destructive polysynovitis observed in classical TNF overexpression models, mice overexpressing tmTNF developed axial and peripheral joint disease with synovitis, enthesitis, and osteitis. Histological and radiological assessment evidenced marked endochondral new bone formation leading to joint ankylosis over time. SpA-like inflammation, but not osteoproliferation, was dependent on TNF-receptor I and mediated by stromal tmTNF overexpression. Collectively, these data indicate that TNF can drive distinct inflammatory pathologies. We propose that tmTNF is responsible for the key pathological features of SpA.
33321234 Ceramic-on-ceramic cementless total hip arthroplasty in patients aged 40 years or under: D 2021 Feb INTRODUCTION: Underlying diseases, bone deformities and polyethylene wear affect outcome in young patients undergoing total hip arthroplasty (THA). These issues are not widely confirmed for ceramic - on-ceramic THA, particularly regarding cup fixation. Therefore, we did a retrospective long-term investigation on a large population of cementless ceramic-on-ceramic THA in patients aged 40 years or younger aiming to analyze: 1) the complication rate; 2) clinical results; and 3) survival for cup loosening with regard to their preoperative conditions. HYPOTHESIS: Cup loosening could be related to preoperative diagnosis in young patients with a cementless ceramic-on-ceramic THA. PATIENTS AND METHODS: Two hundred and seven hips in 171 patients (97 men and 74 women) underwent a cementless ceramic-on-ceramic THA at a mean age of 31.6±6.8 years. The most frequent diagnoses were avascular necrosis (AVN) of the femoral head (74 hips), pediatric hip diseases (35 hips), severe congenital hip dysplasia (CHD) (31 hips), juvenile rheumatoid arthritis (30 hips) and mild CHD (26 hips). The prosthesis included a press-fit metal backed cup with a hydroxyapatite coating and a macrotexture surface on either the equatorial region (93 cups) or the entire surface of the shell (114 cups). Ceramics were made of pure alumina and had a femoral head size of 28 (60 hips) or 32mm (147 hips). In all cases same the straight cementless tapered stem was inserted. RESULTS: There were three early dislocations, one requiring cup revision No hip was revised due to infection, ceramic fracture, or femoral component loosening. Eight cups were revised for aseptic loosening (3,8%). The mean preoperative Harris Hip score was 52.8±6.2 and 93.4±6.9 at the end of follow-up. It was better in AVN (95.7±2.3) and worst in severe CHD (88.8±11.8) (p=0.001). If the end-point was cup aseptic loosening, the survival rate at 17 years was 95.1% (95% CI: 91.3-98.9), 100% for AVN and post-traumatic arthritis, and 86.8% (95% CI: 74.9-98.7) for severe CHD. CONCLUSIONS: Despite diagnoses frequently causing technical difficulties at the surgery, outcome of cementless ceramic-on-ceramic THA in patients under the age of 40 years is satisfactory over ten years of follow up. Cup aseptic loosening was the main cause of failure and appears more related to the initial hip diseases than the age of the patient. LEVEL OF EVIDENCE: III; retrospective comparative study.
32610558 The Potential Effect of Aberrant Testosterone Levels on Common Diseases: A Mendelian Rando 2020 Jun 29 Testosterone has historically been linked to sexual dysfunction; however, it has recently been shown to affect other physical and mental attributes. We attempted to determine whether changes in serum testosterone could play a role in chronic or degenerative diseases. We used two separate genetic instruments comprising of variants from JMJD1C and SHBG regions and conducted a two-sample Mendelian randomization for type II diabetes (T2D), gout, rheumatoid arthritis (RA), schizophrenia, bipolar disorder, Alzheimer's disease and depression. For the JMJD1C locus, one unit increase in log transformed testosterone was significantly associated with RA (OR = 1.69, p = 0.02), gout (OR = 0.469, p = 0.001) and T2D (OR = 0.769, p = 0.048). Similarly, one unit increase in log transformed testosterone using variants from the SHBG locus was associated with depression (OR = 1.02, p < 0.0001), RA (OR = 1.254, p < 0.0001) and T2D (OR = 0.88, p < 0.0001). Our results show that low levels of serum testosterone levels may cause gout and T2D, while higher than normal levels of testosterone may result in RA and depression. Our findings suggest that fluctuations in testosterone levels may have severe consequences that warrant further investigation.
32765484 Increasing the Chemical Variety of Small-Molecule-Based TLR4 Modulators: An Overview. 2020 Toll-Like Receptor 4 (TLR4) is one of the receptors of innate immunity. It is activated by Pathogen- and Damage-Associated Molecular Patterns (PAMPs and DAMPs) and triggers pro-inflammatory responses that belong to the repertoire of innate immune responses, consequently protecting against infectious challenges and boosting adaptive immunity. Mild TLR4 stimulation by non-toxic molecules resembling its natural agonist (lipid A) provided efficient vaccine adjuvants. The non-toxic TLR4 agonist monophosphoryl lipid A (MPLA) has been approved for clinical use. This suggests the development of other TLR4 agonists as adjuvants or drugs for cancer immunotherapy. TLR4 excessive activation by a Gram-negative bacteria lipopolysaccharide (LPS) leads to sepsis, while TLR4 stimulation by DAMPs is a common mechanism in several inflammatory and autoimmune diseases. TLR4 inhibition by small molecules and antibodies could therefore provide access to innovative therapeutics targeting sepsis as well as acute and chronic inflammations. The potential use of TLR4 antagonists as anti-inflammatory drugs with unique selectivity and a new mechanism of action compared to corticosteroids or other non-steroid anti-inflammatory drugs fueled the search for compounds of natural or synthetic origin able to block or inhibit TLR4 activation and signaling. The wide spectrum of clinical settings to which TLR4 inhibitors can be applied include autoimmune diseases (rheumatoid arthritis, inflammatory bowel diseases), vascular inflammation, neuroinflammations, and neurodegenerative diseases. The last advances (from 2017) in TLR4 activation or inhibition by small molecules (molecular weight <2 kDa) are reviewed here. Studies on pre-clinical validation of new chemical entities (drug hits) on cellular or animal models as well as new clinical studies on previously developed TLR4 modulators are reported. Innovative TLR4 modulators discovered by computer-assisted drug design and an artificial intelligence approach are described. Some "old" TLR4 agonists or antagonists such as MPLA or Eritoran are under study for repositioning in different pharmacological contexts. The mechanism of action of the molecules and the level of TLR4 involvement in their biological activity are critically discussed.
32252501 Safety of tumor necrosis factor inhibitor use in patients with concomitant malignancy. 2020 Jul BACKGROUND/AIMS: Safety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use. METHODS: Chart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves. RESULTS: Thirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158). CONCLUSIONS: Our findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.
33072101 Hsp65-Producing Lactococcocus lactis Prevents Antigen-Induced Arthritis in Mice. 2020 Oral tolerance is the physiological process that enables the immune system to differentiate between harmless dietary and microbiota antigens from pathogen derived antigens. It develops at the mucosal surfaces and can result in local and systemic regulatory and anti-inflammatory effects. Translation of these benefits to the clinical practice faces limitations involving specificity and doses of antigen as well as regimens of feeding. To circumvent these problems, we developed a recombinant Hsp65 delivered by the acid lactic bacteria Lactococcus lactis NCDO 2118 directy in the intestinal mucosa. Hsp65 is a ubiquitous protein overexpressed in inflamed tissues and capable of inducing immunoregulatory mechanisms. L. lactis has probiotic properties and is commonly and safely used in dairy products. In this study, we showed that continuous delivery of HSP65 in the gut mucosa by L. lactis is a potent tolerogenic stimulus inducing regulatory CD4(+)LAP(+) T cells that prevented collagen-induced and methylated bovine serum albumin-induced arthritis in mice. Clinical and histological signs of arthritis were inhibited as well as levels of inflammatory cytokines such as IL-17 and IFN-γ, serum titers of anti-collagen antibodies and rheumatoid factor. Oral administration of L. lactis induced alterations in microbiota composition toward an increased abundance of anaerobic bacteria such as Bifidobacterium and Lactobacillus. Tolerance to HSP65 and arthritis prevention induced by the recombinant L. lactis was associated with increase in IL-10 production by B cells and it was dependent on LAP(+) T cells, IL-10 and TLR2 signaling. Therefore, HSP65-producing treatment induced effective tolerance and prevented arthritis development suggesting it can be used as a therapeutic tool for autoimmune diseases.