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• Colchicine is not superior to standard of care in reducing the risk of mortality, clinical worsening or mechanical ventilation in hospitalized patients with COVID-19 pneumonia. • Colchicine should be administered with caution in the advanced phases of the disease. • Older patients with comorbidities (pre-existent heart, lung, upper-gastrointestinal, lower-gastrointestinal diseases, and cancer) are characterized by worse outcome. To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F<275 mmHg (P=0.005), AST>40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group. Colchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a systemic inflammatory disease, primarily involving the upper and lower respiratory tract and kidneys. It is a relatively uncommon condition, characterized by necrotizing granulomatous vasculitis of small- and medium-sized vessels and the presence of anti-neutrophil cytoplasmic antibodies in the serum as defined in the Chapel Hill Consensus Conference 2012. GPA presents a wide spectrum of manifestations and remains one of the most challenging diagnostic dilemmas in clinical medicine. From common respiratory and neurological symptoms to infrequent cardiac complications, this fatal systemic illness is difficult to distinguish from infectious etiologies, and it is often mistaken for an isolated complaint. We report a case of granulomatosis with polyangiitis in a patient with persistent frontal headache, for a very long time considered as migraine versus tension-type headache. [ABSTRACT FROM AUTHOR]

Background CD28neg T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28neg T-cell populations in these patients. Methods Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementaritydetermining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. Results Abatacept induces a decrease of the percentage and number of CD4+CD28neg T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. Conclusions Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4+CD28neg T cells. [ABSTRACT FROM AUTHOR]

To better understand the kinetics of the delayed reconstitution of peripheral CD4+ T-cells after depletion with a single administration of alemtuzumab (AL) for renal transplantation, we evaluated in these patients the percentage and absolute number of recent thymic emigrants (RTEs) CD4+ T cells, together with naive and memory subsets, defined by the analysis of CD31, CD45RA and CCR7 expression, and compared with patients treated with a nondepleting protocol based on basiliximab, and with healthy controls. In AL-treated patients, the number of circulating CD4+ T cells was greatly reduced 1 year after the infusion ( P < 0.01), but the proportions of central memory, effector memory and terminally differentiated effector memory subsets among CD4+ cells were significantly increased. On the contrary, the proportion and the absolute number of naïve CD4+ T cells, although progressively increasing with time, were severely reduced. In particular, the absolute number of RTEs had only very slight increase with time ( P = 0.049) and was dramatically low 1 year after the therapy ( P < 0.01 vs. healthy controls; P < 0.05 vs. basiliximab-treated transplant recipients). These data suggest that a prolonged defective thymic output after AL therapy in renal transplant recipients is one of the main causes of the persistent CD4+ T-cell lymphopenia observed in these patients. [ABSTRACT FROM AUTHOR]

The article discuses a study conducted by the authors on T-cell in rheumatoid patients with clinical response to rituximab. Topics discussed include demonstration of reduction in circulating CD4+ T-cell number in rheumatoid patients while responding to rituximab, the risk associated with opportunistic infections and suggestions for clinicians in decision making regarding rituximab therapy.

The coexistence of systemic sclerosis (SSc) and multiple sclerosis (MS) in the same patient has been described in few cases. We refer here a further case of association between these diseases, which highlight the difficulty of treating such patients. A 57-year-old male with relapsing-remitting MS since 20 years, shortly after having received high-dose corticosteroids for a relapse of MS, suddenly developed SSc, with onset of Raynaud phenomenon simultaneous to that of scleroderma skin involvement, new appearance of accelerated arterial hypertension, and rapidly progressive oliguric renal failure, indicative of scleroderma renal crisis, that was controlled with ramipril, irbesartan and amlodipin. A further disabling relapse of MS was treated with interferon-beta, but 19 months later he developed multiple severe digital necrotic ulcers, that resolved with interferon discontinuation and therapy with iloprost. This case report shows that some form of treatment useful for MS might enhance the manifestations of SSc. [ABSTRACT FROM AUTHOR]

A strong association between the human leucocyte antigen (HLA)-B*58:01 allele and allopurinol-associated severe cutaneous adverse reactions (SCAR) has been reported. A screening for HLA-B*58:01 before allopurinol has been suggested in guidelines for management of gout. HLA-B*58:01 screening is generally based on molecular biology methods that may be not suitable for wide application. We have retrospectively evaluated the performance on a rapid flow cytometry (FCM) test, based on the use of a monoclonal antibody specific for HLA-B17, an antigen that can be split into HLA-B*57 and -B*58 alleles by molecular biology testing, which is used to screen for HLA-B*57:01 before prescription of the antiretroviral agent abacavir in HIV-positive patients. Among 475 samples that were analysed by FCM and by molecular biology test as gold standard, 2 out of 89 false negative tests for HLA-B*58:01 were found. The sensitivity was 97.8 % and the negative predictive value was 98.9 %. We have shown that a FCM test can identify almost all HLA-B*58:01 positive individuals. As FCM laboratories are more widely available than molecular biology ones, this approach could be used to reduce the risk for allopurinol-induced SCAR. Where both facilities are available, a two-step strategy (FCM as screening, molecular biology for confirmation) may reduce the cost of the screening. [ABSTRACT FROM AUTHOR]

Type I IFN (IFN-I) was firstly described in 1957 as a soluble factor responsible for viral resistance in vitro. Today, it is well known that the IFN-I family comprises a wide number of cytokines with different modulatory effects on angiogenesis, cell growth, fibrosis, and apoptosis. However, one of the most important functions of IFN-I is the capability to trigger a complex array of cellular responses that result in a host-protective antiviral response. For this reason, IFN-I can be considered a “director” of protective immune responses. The recent finding of the so-called interferon signature in patients suffering from different autoimmune diseases has underlined its possible role in the pathogenesis of these diseases. On the other hand, IFN-α/β is reported to be efficacious in the treatment of some autoimmune and infectious diseases not responsive to conventional therapy. On these occasions, the treated patients often start or increase autoantibody production supporting the role of IFN as inducer of an autoimmune response. In this review, we will underline recent acquisitions about IFN-I biology, with a focus on the relevance of the induction of some autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, dermato/polymiositis, and Sjogren's syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Glucagon-like peptide 1-receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 inhibitors (incretin enhancers) have been recently introduced in the treatment of diabetes mellitus. In particular, incretin mimetics seems to have ancillary antioxidant/antinflammatory properties that might be involved in endothelial protection.Aim: To investigate the effect of incretin mimetic therapy (liraglutide, exenatide) given to 11 patients with type 2 diabetes mellitus, on circulating endothelial progenitor cells (EPCs) (bone marrow-derived cells possibly participating in neovascularization and endothelial protection and repair) and capillary density.Methods: Four diabetic patients were treated with exenatide (5 μg twice daily for 4 weeks and then 10 μg twice daily for 3 weeks) and 7 with liraglutide (0.6 mg per day for 1 week and then 1.2 mg per day for 3 weeks). Peripheral venous blood samples were obtained before treatment (basal) and after 4 week in patients treated with liraglutide, and after 4 and 7 weeks in patients treated with exenatide, since drug titration is usually longer. EPCs were evaluated by flow cytometry as CD34+/KDR+ cells. Capillary density was evaluated by videomicroscopy, before and after venous congestion, in the dorsum of the 4th finger.Results: Patients treated with liraglutide (6 males 1 female, age 54 ± 12 years) showed a decrease in body mass index and blood pressure during treatment, while patients treated with exenatide (3 males 1 female, age 57 ± 6 years) did not show any relevant change. EPCs were significantly increased after treatment with exenatide, but not after treatment with liraglutide. Capillary density was slightly increased only after 4 weeks of treatment with exenatide, however the increase was no longer present at the final evaluation.Conclusions: Treatment with exenatide, but not with liraglutide, was able to increase the number of circulating EPCs, possibly through an antioxidative/antiinflammatory effect. [ABSTRACT FROM AUTHOR]

Background and objective:Different components of the immune system, including innate and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes – TREGs) may be involved in the development of hypertension, vascular injury and inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular oxidative stress. Our objective was to investigate possible relationships between T-lymphocyte subtypes and systemic and microvascular oxidative stress in a population of normotensive subjects and hypertensive patients. Patients and methods:In the present study we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. A peripheral blood sample was obtained before surgery for assessment of T lymphocyte subpopulations by flow cytometry and circulating indices of oxidative stress. Results:A significant direct correlation was observed between Th1 lymphocytes and reactive oxygen species (ROS) production (mainly in microvessels). Additionally, significant inverse correlations were observed between ROS and total TREGs, or TREGs subtypes. Significant correlations were detected between circulating indices of oxidative stress/inflammation and indices of microvascular morphology/Th1 and Th17 lymphocytes. In addition, a significant inverse correlation was detected between TREGs in subcutaneous small vessels and C reactive protein. Conclusions:Our data suggest that TREG lymphocytes may be protective against microvascular damage, probably because of their anti-oxidant properties, while Th1–Th17 lymphocytes seem to exert an opposite effect, confirming an involvement of adaptive immune system in microvascular damage. [ABSTRACT FROM PUBLISHER]

The aim of this paper was to look for predictors of abatacept (ABA) therapy discontinuation in patients with rheumatoid arthritis (RA). Seventy-one RA patients treated with ABA were followed up. Demographical, clinical, and laboratory parameters of the patients, including peripheral blood T and B cell populations, different rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies isotypes, and serum free light chains were evaluated. Comparing patients who discontinued ABA with those still in therapy we observed: a higher proportion of smokers (51.9 vs 25.6 %; p = 0.03); a non significant lower proportion of anti-cyclic citrullinated peptide positivity (76 vs 89.5 %; p = 0.13); a lower proportion of terminally differentiated effector memory cells (TDEM) among total CD8+ T lymphocytes at baseline (22.0 % (7.8-39.2) vs 38.7 % (20.7-55.9); p = 0.002). Logistic multivariate analysis showed that only the proportion of CD8+TDEM T cells was an independent predictive factor of therapy discontinuation (OR (95 % IC) = 6.2 (1.2 to 30.8); p = 0.026). Receiver-operating characteristic analysis showed a significant performance of this biomarker for prediction of therapy discontinuation (using a cut-off of 30.6 %: AUC: 0.760 ± 0.07; p = 0.002). Patients with a low proportion of CD8+TDEM at baseline had a higher probability of discontinuing the treatment during time (log-rank test: p < 0.01). T cell characterization for identification of TDEM CD8+ T cells might be a useful test to predict discontinuation of ABA therapy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "CD81 T cell profiles in patients with rheumatoid arthritis and their relationship to disease activity," by H. Carvalheiro and colleagues in the 2015 issue.

Objective: The study aims to obtain more information about the immune deficit of common variable immunodeficiency (CVID) patients. Materials and Methods: A new real-time PCR assay was used to quantify T and B lymphocyte mobilization from the production and maturation sites through the detection of T cell receptor excision circles (TRECs) and kappa-deleting recombination circles (KRECs) and to allow the estimation of the average number of B cell divisions. T and B lymphocyte subsets were analyzed by flow cytometry. Results: The number of TREC lymphocytes, which depends on age and gender, was significantly reduced in CVID patients. Similarly, KREC concentration was lower than in controls. Classification of patients according to the percentage of memory switched B cells showed that patients belonging to MB2 group and therefore with conserved B cell maturation have the lowest new B cell output but increased average peripheral divisions, leading to the highest B cell number. Conclusions: TREC and KREC quantification can be helpful for a more complete and informative understanding of a heterogeneous disease such as CVID. [ABSTRACT FROM AUTHOR]

Objectives. To validate the clinical significance of anti-IFI16 autoantibodies in SSc and assess their associations with serological markers of SSc.Methods. A semi-quantitative ELISA was used to detect anti-IFI16 autoantibodies in the sera of 344 SSc patients from seven Italian hospitals and 144 healthy controls. SSc-associated autoantibodies [anti-RNA polymerase III (anti-RNAP III) antibodies, anti-centromere, anti-topo I] and IF patterns were evaluated using commercial assays. Statistical analyses were performed to test clinical and serological associations.Results. The results of this study confirm a significant prevalence (29%) of anti-IFI16 antibodies in the SSc population (n = 344). Anti-IFI16 antibodies were also detected in 30% of the SSc patients who tested negative for both ACAs and anti-topo I (anti-Scl70) antibodies. In this subgroup of patients, anti-IFI16 antibodies were significantly associated with the limited cutaneous form of SSc with a sensitivity of 40% and a specificity of 81%. Moreover, analysis of the distribution of anti-RNAP III antibodies vs anti-IFI16 in the same SSc population showed that they were mutually exclusive. IIF revealed no association between anti-IFI16 and fluoroscopic patterns, due to a lack of IFI16 autoantigen in HEp-2 cells. Anti-IFI16 antibody levels were also significantly associated with heart involvement.Conclusions. Anti-IFI16 autoantibodies are frequently detected in SSc, displaying clinical and laboratory associations, and being particularly useful for diagnosis and disease classification in patients who are negative for other SSc serological markers. [ABSTRACT FROM PUBLISHER]

Few data are available to assess the efficacy of rehabilitative interventions in systemic sclerosis (SSc). We refer here the results of an individualized rehabilitation program in 16 patients with SSc. In particular, when possible, the number of patients who achieved a minimal clinically important difference (MCID) was determined. Results were evaluated taking advantage of the development of validated questionnaires and tests to assess quality of life (QOL) and disability in SSc. At the end of a period of 4 months of observation, 69% and 62% of patients reported an improvement of the physical and mental components of the SF-36 higher than the MCID (as established in other rheumatic conditions). Analogously, an improvement of the impact of respiratory disease on patients’ QOL, as assessed by the Saint George’s Respiratory Questionnaire, was perceived by 67% of them. These results might be explained by better exercise tolerance, which was suggested by the significant reduction of the heart rate and of a visual analogue scale for dyspnoea at the end of the 6-min walking test. Finally, a statistically significant improvement of hand mobility, as assessed by the hand mobility in scleroderma test was obtained. This study suggests that a significant proportion of patients with SSc experience an improvement in their perception of QOL, a better exercise tolerance, and a better hand mobility after a rehabilitation program consisting by a 2-week period of daily individual 30-min sessions as outpatient, followed by at-home exercise program. [ABSTRACT FROM AUTHOR]