The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases

Dysregulation of the intestinal epithelial barrier in genetically susceptible individuals may lead to both intestinal and extraintestinal autoimmune disorders. There is emerging literature on the role of microbiota changes in the pathogenesis of systemic rheumatic diseases such as rheumatoid arthritis, spondyloarthropathies, and connective tissue diseases. Although the role of the gastrointestinal tract in the pathogenesis of spondyloartropathies is well defined and many studies underline the importance of gastrointestinal inflammation in modulating local and systemic inflammation, the data are inconclusive regarding the effect of dysbiosis on rheumatoid arthritis and connective tissue diseases. This review aims to summarize current data on the role of the gastrointestinal involvement and intestinal microbiota in the pathogenesis of systemic rheumatic disease

One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet's disease refractory to standard immunosuppressive drugs

Abstract The aim of the study was to assess the long-term efficacy and safety of Infliximab therapy in the treatment of patients with Behçet’s disease refractory to standard immunosuppressive agents. Twenty-one patients that did not respond to corticosteroids and to at least one immunosuppressant (cyclosporin, methotrexate, azathioprine, cyclophosphamide) for the presence of ocular and/or CNS involvement were enrolled. Eighteen patients completed the study up to 54 weeks. Stable doses of prednisone (<10 mg/day) were permitted, immunosuppressants were discontinued at least 4 weeks prior baseline visit. The patients received three infusions of 5 mg/kg Infliximab (at weeks 0, 2 and 6) and then infusions of 5 mg/kg Infliximab every 8 weeks. At each visit data on clinical symptoms, response to therapy and adverse events were collected. The primary outcome of interest was to assess the clinical efficacy (total or partial recovery) of infliximab. Secondary end points were to evaluate quality of life and to monitor the safety of the drug. Eighteen patients achieved a total remission. Two patients achieved a partial remission and relapsed after 3 months from discontinuation of therapy. Infliximab was well tolerated throughout the study. A case of non-Hodgkin lymphoma was observed within 6 months. Minor side effects were headache, dizziness, tachycardia that regressed spontaneously and did not entail interruption. Anti-nuclear antibodies were not detected during the period of observation

CD3 immunohistochemistry is helpful in the diagnosis of giant cell arteritis

To evaluate whether CD3 staining performed routinely on temporal artery biopsy specimens might improve the sensitivity of temporal artery biopsy in patients with biopsy-negative GCA

A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease

OBJECTIVES: Behçet's disease has been historically classified as a Th1 disease. The recently described IL-17/IL-23 pathway seems to play an important role in many inflammatory diseases and in the intestinal abnormalities of AS and CD. The aim of the present study was to evaluate the IL-17/IL-23 axis in parallel with Th1 and IL-27 response in the intestine of patients with BD and gastrointestinal abnormalities. METHODS: Quantitative TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) was utilised for all determinations on ileal biopsy specimens obtained from BD, AS and CD patients. The serum levels of Th1 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay. RESULTS: A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease. CONCLUSIONS: Although BD shares clinical manifestations with both CD and AS, the immunologic abnormalities seen in the intestine are quite different, indicating that other immune mechanisms should be taken into account

Worldwide Interest in Vitamin D, Negative Effects on Kidneys, and Bone Density: Analysis of Google Trends Data

Background: Besides its role in calcium homeostasis and bone mineralization, vitamin D may also reduce the risk of cancer, cardiovascular and autoimmune diseases. Excessive vitamin D intake can lead to life-threatening hypercalcemia and toxicity, however. Here, we wanted to determine the relative search volume (RSV) of interest in vitamin D and its adverse biological effects (hypercalcemia, renal failure, kidney stones, bone density).Methods: We used data from Google Trends to assess changes in RSV trends across the world's regions. Data were extracted via the search terms "cholecalciferol", "ergocalciferol, "hypercalcemia", "acute renal failure", "kidney stones", and "bone density" from queries in English from 1 January 2004 to 1 October 2018 in the tool's related query database. Statistical analysis was performed using SPSS (R) 22.0 for Windows (IBM Inc., Armonk, NY, USA, 10504-1722).Results: There was a correlation between the RSV of cholecalciferol and ergocalciferol (Spearman's correlation) and the RSV of hypercalcemia, renal failure, kidney stones, and bone density. As measured by the change in RSV score, the trend for interest in kidney stones increased more rapidly than that for the other search terms. There was a positive correlation between the RSV score for cholecalciferol (or ergocalciferol) and renal failure and between the RSV score for cholecalciferol (or ergocalciferol) and kidney stones, whereas there was a negative correlation between cholecalciferol and hypercalcemia. The interest of ergocalciferol increased in parallel with the interest in bone density. The highest concentration of interest in cholecalciferol occurred in North America, Europe, India and Australia, whereas interest in ergocalciferol was greater in Central and South America, Spain, and Thailand. Interest in kidney stones was greater than cholecalciferol in North America, Brazil, India, and Australia, while interest in bone density was greater than cholecalciferol in North America, Brazil, Italy, Spain, South Africa, and Australia.Conclusions: In the pre-pandemic COVID-19 (COronaVIrus Disease 19) era, our preliminary results showed a positive correla-tion between global interest in cholecalciferol and kidney stones and renal failure, respectively. However, we found an unexpected negative correlation between global interest in cholecalciferol and hypercalcemia. Additionally, we found a positive correlation between global interest in ergocalciferol and bone density. These correlations can inform health interventions and education

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR = 3.36; 95% CI = 1.46-7.74; p = .005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR = 6.47, 95% CI = 2.58-16.26; p < .0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR = 7.06, 95% CI = 0.07-2.19; p = .002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38 ± 28.49 μmol/L) compared to SLE patients HLA-C1 negative (108.37 ± 86.09 μmol/L) (p = .03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients

A CLUSTER OF SARS-COV-2 DELTA VARIANT OF CONCERN ADDITIONALLY HARBORING F490S, NORTHERN LOMBARDY, ITALY

The Delta variant of concern (VOC) of SARS-CoV-2 has become dominant worldwide. We report here a cluster caused by B.1.617.2 harboring the additional mutation of concern (MOC) F490S. Infection occurred in 5 fully vaccinated subjects between the ages of 47 and 84. The immune escape mutation F490S, first identified in the Lambda VOI, appears to impair vaccine efficacy and is rapidly increasing in prevalence worldwide