Early Vascular Aging in Normotensive Patients With Systemic Lupus Erythematosus

Connective tissue diseases, like systemic lupus erythematosus (SLE), are associated with early and accelerated atherosclerosis. Recently, the concept of “early vascular aging” (EVA) has been more widely accepted. Aortic stiffness is one of the important markers of EVA. We evaluated EVA and subclinical atherosclerosis, by measuring aortic pulse wave velocity (aPWV) and carotid intima–media thickness (cIMT), in 50 normotensive patients with SLE (mean age: 39 ± 12 years). We compared these participants with 50 age- and sex-matched patients with essential hypertension (EH) and 20 healthy controls. Each participant underwent 24-hour ambulatory blood pressure monitoring (ABPM), aPWV, and cIMT me…

Giant cell arteritis associated with chronic active Epstein-Barr virus infection

Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.

Multifunctional Carrier Based on Halloysite/Laponite Hybrid Hydrogel for Kartogenin Delivery

[Image: see text] A novel carrier system based on halloysite nanotubes (HNT), for the potential intraarticular delivery of kartogenin (KGN) by means laponite (Lap) hydrogel (HNT/KGN/Lap), is developed. The drug was first loaded into HNT, and the hybrid composite obtained was used as filler for laponite hydrogel. Both the filler and the hydrogel were thoroughly investigated by several techniques and the hydrogel morphology was imaged by transmission electron microscopy. Furthermore, the gelating ability of laponite in the presence of the filler and the rheological properties of the hybrid hydrogel were also investigated. The kinetic release of kartogenin from HNT and HNT/Lap hybrid hydrogel …

The role of innate and lymphoid IL-22-producing cells in the immunopathology of primary Sjögren's syndrome

In primary Sjögren's syndrome (pSS) a complex of interconnections between epithelial barrier, innate and adaptive immunity occurs. IL-22 is a pleiotropic cytokine that in pSS may be placed at the intersection of the adaptive and innate branches of immunity. Some evidence suggests that, in pSS, IL-22 may play a prominent pro-inflammatory role driving the early phase of tissue and systemic inflammation and participating in the self-perpetuation of disease. Despite contradictory data in literature about the role of NK cells in pSS, recent data also suggest an important contribution of this subset of cells of the innate immune system in the development and perpetuation of inflammation. Here, we…

FRI0162 IL-9 Over-Expression and Th9 Polarization Immunologically Characterizes the Subclinical Gut Inflammation of Patients with Psoriatic Arthritis

Background Subclinical gut inflammation has been demonstrated in patients with psoriatic arthritis (PsA) suggesting a role for the gut in the pathogenesis of inflammation in these patients. A key role for the IL-23, IL-17, IL-22 and IL-9 in the pathogenesis of psoriasis and psoriatic arthritis has been suggested, the immunologic abnormalities underlying subclinical gut inflammation in PsA are still undefined however. Objectives This study was undertaken to investigate the expression and tissue distribution of IL-23 and of Th17,Th22 and Th9 related molecules in the subclinical gut inflammation of patients with PsA. Methods Gut inflammation was assessed accordingly to De Vos et al (1). Quanti…

Tocilizumab therapy for unresponsive pulmonary arterial hypertension in a patient with Takayasu arteritis

A 46-year-old female Caucasian patient was referred to our unit with upper extremity claudication, dyspnoea [New York Heart Association (NYHA) Class III], and weight loss. On physical examination, ...

Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis

Objective To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mon…

Behcet's disease is a multisystem disease in which there is evidence of immunological dysregulation. It has been proposed that γ/δ T cells are involved in its pathogenesis. The aim of the present study was to assess the capacity of γ/δ T cells with phenotype Vγ9/Vδ2, from a group of Italian patients with Behcet's disease, to proliferate in the presence of various phosphoantigens and to express tumour necrosis factor (TNF) and IL-12 receptors. Twenty-five patients and 45 healthy individuals were studied. Vγ9/Vδ2 T cells were analyzed by fluorescence activated cell sorting, utilizing specific monoclonal antibodies. For the expansion of Vγ9/Vδ2 T cells, lymphocytes were cultured in the presenc…

Cognitive impairment in Behçet's disease patients without overt neurological involvement

We investigated the prevalence of cognitive impairment in patients with Behc¸et’s disease (BD) without overt neurological involvement. The influence of disease duration, disease activity, prednisone dosage, and anxiety and depression levels was evaluated. Twenty-six consecutive BD outpatients and 26 healthy controls matched for age, education and sex completed a comprehensive neuropsychological battery including tests of memory, visuospatial and constructional abilities, language, attention and psychomotor speed, non-verbal reasoning and executive functioning. The Hamilton scales for anxiety and depression were administered. Disease activity was assessed using the Behc¸et’s Disease Current …

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…

Phenotype and functional changes of Vgamma9/Vdelta2 T lymphocytes in Behçet's disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity

INTRODUCTION: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vgamma9/Vdelta2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity. METHODS: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vgamma9/Vdelta2 T lymphocytes by means of fluores…

Expression of Interleukin-32 in the Inflamed Arteries of Patients With Giant Cell Arteritis

Objective Giant cell (temporal) arteritis (GCA) is a vasculitis that mainly affects the large and medium arteries, especially the branches of the proximal aorta. Interleukin-32 (IL-32) is a recently described Th1 proinflammatory cytokine, and is mainly induced by interferon-γ (IFNγ), IL-1β, and tumor necrosis factor α (TNFα). This study was undertaken to investigate the expression and tissue distribution of IL-32 in artery biopsy specimens from patients with GCA. Methods Quantitative gene expression analysis of IL-32, IL-1β, TNFα, IFNγ, IL-6, and IL-27 was performed in artery biopsy specimens obtained from 18 patients with GCA and 15 controls. Immunohistochemistry analysis was performed to …

Immunoreumatologia

Role of subclinical gut inflammation in the pathogenesis of spondyloarthritis

Subclinical gut inflammation occurring in patients affected by spondyloarthritis (SpA) is correlated with the severity of spine inflammation. Several evidences indicate that dysbiosis occurs in SpA, and that may modulate intestinal permeability and intestinal immune responses. The presence of intestinal dysbiosis is accompanied in SpA patients with the presence of zonulin-dependent alterations of gut-epithelial and gut-vascular barriers. The leakage of epithelial and endothelial surface layers is followed by the translocation of bacterial products, such as lipopolysaccharide and intestinal fatty acid binding protein, in the systemic circulation. These bacterial products may downregulate the…

Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables

Objective: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA).Method: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1β…

Gut inflammation in spondyloarthritis

Abstract Spondyloarthritis (SpA) is a group of related diseases sharing common etiopathogenic mechanisms and clinical manifestations supported by a complex genetic predisposition. Gut inflammation is present in patients with SpA including patients showing clinically evident intestinal inflammation in the form of Crohn's disease or ulcerative colitis and patients who despite the absence of signs and symptoms of intestinal inflammation display a subclinical gut inflammation. Emerging evidence suggests that subclinical gut inflammation in patients with SpA, apparently driven by intestinal dysbiosis, is not the consequence of the systemic inflammatory process but rather an important pathophysio…

The craniovertebral junction in rheumatoid arthritis: State of the art

Rheumatoid arthritis (RA) is a chronic inflammatory disorder, characterized by polyarticular inflammation causing progressive joint damage and disability. The mechanisms underlying its pathogenesis involve activation of innate and adaptive immunity, microvascular endothelial cell activation, and inflammatory infiltration of lymphocytes and monocytes into the synovium. Spinal involvement in RA is not typical; when it occurs, the main radiological features are (1) atlantoaxial subluxation (AAS), which is the most typical form of cervical spine involvement; (2) cranial settling—also known as basilar impression, atlantoaxial impaction or superior migration of the odontoid—which is the most seve…

ASSOCIATION OF RENAL RESISTIVE INDEX WITH MARKERS OF EXTRARENAL VASCULAR CHANGES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Introduction: Recent data suggest that renal hemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RRI), may be associated with systemic vascular changes. However, limited and conflicting data exist about the relationship between aortic stiffness and RI in autoimmune diseases, like systemic lupus erythematosus (SLE). Aim: To evaluate the relationship between RRI and arterial stiffness, assessed by aortic pulse wave velocity (aPWV), and between RRI and carotid atherosclerosis, evaluated by intima-media thickness (IMT) measurement in patients with SLE. Methods: In this cross-sectional study, we enrolled 39 SLE subjects (mean age 39 years) tha…

New insights into the pathogenesis of giant cell arteritis

Giant cell arteritis (GCA) is an inflammatory chronic disease occurring exclusively in elderly individuals. Until recently, the disease has been considered a unique disease resulting from the interaction in the walls of susceptible arteries, between an unknown infectious agents with local dendritic cells (DCs), activated CD4 T cells and effector macrophages. Recent evidence has shown that this view was too simplistic and has clarified many of the pathogenetic aspects of the disease. Many genetic studies recently published have identified different new genes, including cytokines, adhesion molecules and regulators of innate immunity, as crucial players in the development and progression of GC…

Relationship between transforming growth factor beta1 and progression of hypertensive renal disease.

In this study the role of circulating transforming growth factor beta1 (TGFbeta1) on progression of renal hypertensive disease has been investigated. Fifty consecutive outpatients with essential hypertension were enrolled and divided into three groups, according to their urinary albumin excretion (UAE). Group A comprised 10 hypertensives with UAEor=20 mg/24 h (normoalbuminuric group); Group B included 21 hypertensives with UAE20300 mg/24 h (microalbuminuric group); Group C encompassed 19 hypertensives with UAEor= 300 mg/24 h (proteinuric group). In all patients UAE by immunonephelometric assay, circulating TGFbeta1 by a solid phase specific sandwich ELISA technique, BUN and creatinine by ro…

Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome.

OBJECTIVES: In chronic inflammatory disorders, interleukin (IL)-22 may act either as a protective or as a pro-inflammatory cytokine. At mucosal sites, IL-22 is mainly produced by CD4(+) T cells and by a subset of mucosal natural killer (NK) cells expressing the receptor NKp44 (NKp44(+) NK cells). The aim of this study was to investigate the IL-22 expression in the salivary glands of patients with primary Sjögren's syndrome (pSS). METHODS: Minor salivary gland biopsies were obtained from 19 patients with pSS and 16 with non-specific chronic sialoadenitis. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-17, IL-22, IL-23 and STAT3 (signal transduce…

Phenotype and functional changes of Vγ9/Vδ2 T lymphocytes in Behçet's disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity

Introduction: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α) that has been introduced recently for Behcet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vγ9/Vδ2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity. Methods: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vγ9/Vδ2 T lymphocytes by means of fluorescence-activated cell sorter …

Enhancement of endothelial cell E-selectin expression by sera from patients with active Behçet's disease: moderate correlation with anti-endothelial cell antibodies and serum myeloperoxidase levels.

We studied the in vitro E-selection expression of endothelial cells treated with sera from patients with Behcet's disease (BD) and factors (anti-endothelial cell antibodies, anti-neutrophil cytoplasmic antibodies, cytokines, and myeloperoxidase (MPO) that may contribute to adhesion molecule expression. A total of 21 patients with BD and 27 healthy controls were studied. In vitro E-selectin endothelial cell expression was investigated by ELISA after HUVEC incubation with sera or purified IgG from patients with BD and controls. Increased E-selectin expression was observed when endothelial cells were incubated with sera from patients with active disease or from patients with circulating anti-e…

Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVE: The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS). METHODS: Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments. RESULTS: IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mast …

CORRELATIONS BETWEEN NON INVASIVE RENAL INDEX AND MARKERS OF ATHEROSCLEROSIS IN LUPUS PATIENTS.

Objective: Recent data suggest that renal haemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RI), may be associated with systemic vascular changes in some groups of patients. However, conflicting data exist about the relationship between aortic stiffness and RI in autoimmune disease, like systemic lupus The aim of this study was to evaluate the relationship between RI and arterial stiffness, assessed by aortic pulse wave velocity (aPWV), and carotid atherosclerosis, evaluated by intimal medial thickness measurement(IMT) in patients with SLE. Design and method: Cross-sectional study. We enrolled 39 SLE subjects (mean age 39 years). Each …

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 detecti…

THU0045 IL-25/IL-17RB AXIS IS ACTIVATED AND ASSOCIATED WITH ILC2 EXPANSION IN GRANULOMATOSIS WITH POLYANGIITIS (GPA)

Background: Pathogenesis of Granulomatosis with polyangiitis (GPA) is still unknown. However, it has been observed a skewing of circulating CD4+ T cells toward the Th17 and Th2 phenotype. The pro-inflammatory cytokine interleukin 25 (IL-25) is a member of IL-17 cytokine family associated to the Th2 immune phenotype. Through the receptor IL17RB, IL-25 further sustains the Th2-type immune response and elicits the expansion of the type 2 innate lymphoid cells (ILC2) and M2 macrophages. A pathogenic role of the innate lymphoid cells in GPA has been recently demonstrated; however, the relevance of IL-25 in this condition remains unexplored. Objectives: Aim of the study was to evaluate the expres…

Vascular health in subjects with rheumatoid arthritis: assessment of endothelial function indices and serum biomarkers of vascular damage

Background The cardiovascular risk (CVD) in patients with rheumatoid arthritis (RA) is 1.5–2 times higher than that in individuals of the same age and sex. Aims To analyse the degree of endothelial dysfunction, the atherogenic immunoinflammatory serum background and the relationships among some vascular indices, cardiovascular comorbidities, and cognitive performance in subjects with RA. Patients and methods All consecutive patients with a rheumatoid arthritis diagnosis admitted to the Rheumatology Ward of “Policlinico Paolo Giaccone” Hospital of Palermo were enrolled from July 2019 to September 2020. We evaluated our patients’ cognitive functions by administering the Mini-Mental State Exam…

A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis

The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated to be of value in reducing AS disease activity in clinical trials. The efficacy and safety of both etanercept and infliximab in patients with ankylosing spondylitis were compared in a 2-year open label randomised study. Our results are consistent with a significant more rapid clinical improvement in the infliximab treated group. Treatment with both etanercept and infliximab at the end of the study was effective, safe, and well tolerated. ©…

Glucocorticoid excess and COVID-19 disease

AbstractThe pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing high and rapid morbidity and mortality. Immune system response plays a crucial role in controlling and resolving the viral infection. Exogenous or endogenous glucocorticoid excess is characterized by increased susceptibility to infections, due to impairment of the innate and adaptive immune system. In addition, diabetes, hypertension, obesity and thromboembolism are conditions overrepresented in patients with hypercortisolism. Thus patients with chronic glucocorticoid (GC) excess may be at high risk of developing COVID-19 infection with a sever…

Correlations between non ivasive renal index and markers of atherosclerosis in lupus patients

Recent data suggest that renal hemodynamic parameters obtained by duplex Doppler sonography, especially the intrarenal resistive index (RI), may be associated with systemic vascular changes in some groups of patients. However, conflicting data exist about the relationship between aortic stiffness and RI in autoimmune disease, like systemic lupus erythematosus, characterized by high and early incidence of atherosclerotic disease. The aim of this study was to evaluate the relationship between RI and arterial stiffness, assessed by aortic pulse wave velocity (aPWV), and carotid atherosclerosis, evaluated by intimal medial thickness measurement (IMT) in patients with SLE. DESIGN: Cross-sectiona…

EARLY VASCULAR AGEING IN NORMOTENSIVE SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS. COMPARISON WITH YOUNG HYPERTENSIVE PATIENTS

Objective: Aortic pulse wave velocity (aPWV), is one of the most important markers of vascular aging. It is well known that connective tissue diseases are associated with accelerated atherosclerosis, but only a few data are available about aPWV in patients with systemic lupus erythematosus (SLE). The aim of this study was to evaluate early vascular aging, assessed by measuring aPWV, in a group of normotensive patients with SLE and to compare these subjects with a group of young essential hypertensive (EH) individuals Design and method: Crosssectional study. We have enrolled 39 normotensive SLE subjects (mean age: 38.7±8.3 years) matched for age with a group of essential hypertensive patient…

The in vitro addition of methotrexate and/or methylprednisolone determines peripheral reduction in Th17 and expansion of conventional Treg and of IL-10 producing Th17 lymphocytes in patients with early rheumatoid arthritis.

The aim of our study was to evaluate methotrexate (MTX) and methylprednisolone (MP) effect on peripheral Th17 and Treg subsets in patients with rheumatoid arthritis (RA). We enrolled 15 patients (10 early RA and 5 long-standing disease) with active RA and 10 age-matched healthy donors as controls. Frequencies of Th17 and Treg were quantified using flow cytometry before and after in vitro addition of MTX, MP or both drugs. Our results showed a reduction in the overall Th17 population followed by an increase in Th17 IL-10+ and Treg, after in vitro treatment of PBMCs with the drugs in patients with early RA. Long-standing disease patients showed a less evident increase in Treg cells and less e…

Pathogenesis of polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause, almost exclusively occurring in people aged over 50 and often associated with giant cell arteritis. The evidence that PMR occurs almost exclusively in individuals aged over 50 may indicate that age-related immune alterations in genetically predisposed subjects contribute to development of the disease. Several infectious agents have been investigated as possible triggers of PMR even though the results are inconclusive. Activation of the innate and adaptive immune systems has been proved in PMR patients as demonstrated by the activation of dendritic cells and monocytes/macrophages and the altered balance betwee…

Over-expression of paneth cell-derived anti-microbial peptides in the gut of patients with ankylosing spondylitis and subclinical intestinal inflammation

OBJECTIVES: Subclinical gut inflammation has been demonstrated in patients with AS. Altered expression of paneth cell (PC) anti-microbial peptides have been reported in the inflamed ileum of patients with Crohn's disease (CD). Here, we investigated the expression of PC-derived peptides in subclinical gut inflammation in AS. METHODS: Multiple adjacent mucosal biopsies from terminal ileum were obtained from 25 patients with AS, 30 CD and 15 healthy controls (HCs). Expression of human α-defensin 5 (HD-5), phospholipase A2 (PLA2), lysozyme and SOX-9 molecules was assessed by quantitative Taqman RT-PCR on mucosal samples. Immunohistochemistry with anti-human HD-5 antibody and genotyping of relev…

EARLY VASCULAR AGING IN NORMOTENSIVE SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS. COMPARISON WITH YOUNG HYPERTENSIVE PATIENTS

Introduction: It is well known that connective tissue diseases, like Systemic Lupus Erythematosus, are associated with early and accelerated atherosclerosis. During the last year, it has well established the concept of ‘‘Early vascular aging’’ (EVA), whose the aortic stiffness represents one of the most important markers. Aim: To evaluate early vascular aging, assessed by measuring Aortic pulse wave velocity (aPWV), as an arterial stiffness index, in a group of normotensive patients with SLE and to compare these subjects with a group of young essential hypertensive (EH) individuals.Methods: In this cross-sectional study we have enrolled 50 normotensive SLE subjects (45 women and 5 men) with…

Interleukin-9 and T helper type 9 cells in rheumatic diseases

Summary Interleukin (IL)-9 is a 28-30 kDa monomeric glycosylated polypeptide belonging to the IL-7/IL-9 family of proteins that bind to a composite receptor consisting of the private receptor IL-9R and the IL-2 receptor, gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL-9R is expressed widely and IL-9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL-9 in promoting cellular and humoral immune responses makes it an important focus of pot…

Expansion of intestinal CD4+CD25highTreg cells in patients with ankylosing spondylitis: A putative role for interleukin-10 in preventing intestinal Th17 response

Objective Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin-2 [IL-2], transforming growth factor β [TGFβ], and IL-10) and transcription factors (FoxP3 and STAT-5) in the ileum of patients with AS. Methods Quantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg-related cytokines (IL-2, TGFβ, and IL-10) and transcription factors (STAT-5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disea…

CD3 immunohistochemistry is helpful in the diagnosis of giant cell arteritis.

Objective. 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. Methods. Two hundred and seventy biopsies were considered for this study, stained with haematoxylin and eosin and with an anti-CD3 antibody. Results. The addition of CD3 staining modified the sensibility and the specificity of the histologic examination in 89.47 and 95.00%, respectively, with a positive and negative predictive values of 97.00 and 79.78%. Conclusion. The addition of CD3 immunostaining to the classic histologic evaluation is accompanied by a significant increase in the sensibility with…

Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies.

Objective To compare the 2 most efficacious therapeutic regimens, intravenous immunoglobulin (IVIG) and anticoagulation with low molecular weight (LMW) heparin plus low-dose aspirin, in women with recurrent pregnancy loss associated with antiphospholipid antibodies (aPL). Methods We examined 40 women with recurrent abortion (at least 3 occurrences) and repeatedly positive test results for anticardiolipin or lupus anticoagulant. The subjects were randomly assigned to treatment with IVIG or LMW heparin plus low-dose aspirin. Both therapies were started when the women were pregnant as documented by a positive urine test. IVIG was stopped at the thirty-first week of gestation, aspirin at the th…

IVIG in APS pregnancy

For more than two decades, the intravenous administration of high doses of IgG pooled from the plasma of healthy donors (immune globulin therapy, also known as ‘IVIG’) has benefited patients with a variety of autoimmune disorders. A potential therapeutic role of IVIG in the prevention of thrombosis and of miscarriages in antiphospholipid syndrome (APS) has been postulated. Multicenter randomized controlled trials attempted to define the role of IVIG in preventing pregnancy complications in APS indicate that simple anticoagulation could not be completely satisfactory, and certain patient subgroups might take advantage of IVIG therapy alone or in combination with heparin.

Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients

Summary Cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of γδ T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). γδ T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse trans…

AORTIC STIFFNESS IS INCREASED IN NORMOTENSIVE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS Abstracts from the 17th National Congress of the Italian Society of Cardiovascular Prevention (SIPREC), Naples, 21-23 March 2019

Introduction: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular (CV) events. A marker of early vascular aging (EVA) is aortic pulse wave velocity (aPWV) which is a measure of arterial stiffness. Aim: To evaluate aPWV and the prevalence of EVA in a group of normotensive patients with SLE and to compare these values with those obtained in age- and gender-matched control subjects. Method: Aortic PWV was measured by a validated oscillometric device (Arteriograph). EVA was identified when the age-adjusted z-score of aPWV exceeded ? 1.96 (EVA1). The aPWV z-score was calculated using the ratio ‘‘Observed PWV–Predicted PWV/SD Predicted’’ and we obt…

Vascular endothelial growth factor gene polymorphisms in Behçet's disease

Objective. To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression. Methods. Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs302…

Long-term anti-tumour necrosis factor therapy reverses the progression of carotid intima–media thickness in female patients with active rheumatoid arthritis

The objective of the study is to evaluate the effect of TNF inhibition on carotid thickness over a 2-year period. 144 women with RA diagnosed according to ACR criteria, without clinical evidence of cardiac and/or vascular disease were enrolled and compared with 78 matched controls. All patients received methotrexate (15–20 mg weekly) for 3 months. Responders (n = 79) continued to be treated with methotrexate, non-responders (n = 40) moved to methotrexate plus a TNF alpha antagonist. Echosonographic studies of carotids were obtained before and after 2-year follow-up. A significant decrease of ca-IMT was observed in anti-TNF-treated patients (P < 0.001); on the other hand, no significant vari…

Histopathology of the gut in rheumatic diseases

The gastrointestinal tract regulates the trafficking of macromolecules between the environment and the host through an epithelial barrier mechanism and is an important part of the immune system controlling the equilibrium between tolerance and immunity to non-self-antigens. Various evidence indicates that intestinal inflammation occurs in patients with rheumatic diseases. In many rheumatic diseases intestinal inflammation appears to be linked to dysbiosis and possibly represents the common denominator in the pathogenesis of different rheumatic diseases. The continuative interaction between dysbiosis and the intestinal immune system may lead to the aberrant activation of immune cells that ca…

Expansion of intestinal CD4+CD25(high) Treg cells in patients with ankylosing spondylitis: a putative role for interleukin-10 in preventing intestinal Th17 response

Objective: subclinical gut inflammation has been demonstrated in ankylosing spondylitis (AS) patients. Aim of this study was to determine the frequency of regulatory CD4+CD25high T cells (Treg), and to evaluate Treg-related cytokines (IL-2, TGF-β, IL-10), and transcription factors (FOXP3 and STAT5) in the ileum of AS patients. Methods: Quantitative gene expression analysis, by rt-PCR, of Treg-related cytokines (IL-2, TGF-β, IL-10) and transcription factor (STAT-5 and FOXP3) was performed on ileal biopsies of 18 AS and 15 active Crohn’s disease (CD) patients, and 15 healthy subjects (HS). Tissue and circulating Treg cells were also analyzed by flow cytometry. Results: A significant up-regula…

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?

Endothelial Progenitor Cells (EPCs) are bone marrow derived cells able to differentiate in mature endothelial cells (EC) contributing to the generation of new vessels, connecting to fibronectin, and forming colonies and/or colony forming units. Since circulating EPCs can be actively considered part of endothelial damage in several cardiovascular diseases and autoimmune disorders the possibility to have a measure for endothelium damage should be considered of interest to predict the patient out-come. At the same time the EPCs proliferative and regenerative role could be considered for therapeutic applications. Studies have been performed to elucidate the role of EPCs in Systemic Sclerosis an…

Blocking TNF in vitro with infliximab determines the inhibition of expansion and interferon gamma production of Vγ9/Vδ2 T lymphocytes from patients with active rheumatoid arthritis. A role in the susceptibility to tuberculosis?

Side effects of TNF neutralisation - mostly infectious complications - were recognized, the most important being pulmonary tuberculosis infections. gamma/ d T cells contribute to protective immune response against mycobacterium tuberculosis.The aim of the present study was to assess the expansion capacity of Vgamma9/Vdelta2 T cells from (tuberculin purified protein derivative (PPD) positive and PPD negative) patients with active rheumatoid arthritis (RA), and to examine the in vitro effect of infliximab on this lymphocyte subset.28 PPD negative RA patients were studied and compared with 14 PPD positive RA patients, 45 PPD-negative and 110 PPD-positive healthy volunteers. Cell separation, ex…

Pentoxifylline Inhibits Vγ9/Vδ2 T Lymphocyte Activation of Patients with Active Behçet's Disease in Vitro

The aim of this study is to evaluate the in vitro effect of pentoxifylline (PTX) on T Vgamma9/Vdelta2 lymphocyte function in Behçets disease (BD). We investigated the effect of PTX on Vgamma9/Vdelta2 T cell expansion and expression of TNFRII receptor and perforin content before and after PTX addition by means of FACS analysis lymphocyte cultures from patients with active and inactive BD and healthy subjects. The addition of PTX at a concentration of 1 mg/ml determined a significant inhibition of cell expansion, a down regulation of TNF receptor expression and inhibited the PMA-induced degranulation of perforin. Taken together these data indicate that PTX is capable of interfering with Vgamm…

IL-9 IN PsA

Objective. To investigate the expression and tis- sue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). Methods. Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA2B272positive patients with ankylosing spondylitis (AS), patients with Crohn’s disease (CD), and healthy controls. Expression and tissue distribu- tion of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohisto- chemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among periph- eral blood, lamina propria, and synovial…

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 dise…

Early vascular aging in normotensive subjects with systemic lupus erythematous. Comparison with young hypertensive patients

early vascular aging

Intestinal dysbiosis and innate immune responses in axial spondyloarthritis

Purpose of review Inflammatory innate and adaptive immune cell responses to commensal bacteria underlie the pathogenesis of human chronic inflammatory diseases. Intestinal dysbiosis has been described in patients with spondyloarthritis (SpA) and seems to be correlated with histologic and immunologic alterations. Purpose of this review is to discuss the relationship occurring between intestinal dysbiosis and innate immune responses in patients with axial SpA. Recent findings Intestinal dysbiosis and differential activation of intestinal immune responses in patients with SpA have been demonstrated. Furthermore, innate cells that appear to be involved in the pathogenesis of SpA may control int…