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1.
Front Immunol ; 15: 1367875, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426109

RESUMO

The tumor microenvironment is a highly complex and dynamic mixture of cell types, including tumor, immune and endothelial cells (ECs), soluble factors (cytokines, chemokines, and growth factors), blood vessels and extracellular matrix. Within this complex network, ECs are not only relevant for controlling blood fluidity and permeability, and orchestrating tumor angiogenesis but also for regulating the antitumor immune response. Lining the luminal side of vessels, ECs check the passage of molecules into the tumor compartment, regulate cellular transmigration, and interact with both circulating pathogens and innate and adaptive immune cells. Thus, they represent a first-line defense system that participates in immune responses. Tumor-associated ECs are involved in T cell priming, activation, and proliferation by acting as semi-professional antigen presenting cells. Thus, targeting ECs may assist in improving antitumor immune cell functions. Moreover, tumor-associated ECs contribute to the development at the tumor site of tertiary lymphoid structures, which have recently been associated with enhanced response to immune checkpoint inhibitors (ICI). When compared to normal ECs, tumor-associated ECs are abnormal in terms of phenotype, genetic expression profile, and functions. They are characterized by high proliferative potential and the ability to activate immunosuppressive mechanisms that support tumor progression and metastatic dissemination. A complete phenotypic and functional characterization of tumor-associated ECs could be helpful to clarify their complex role within the tumor microenvironment and to identify EC specific drug targets to improve cancer therapy. The emerging therapeutic strategies based on the combination of anti-angiogenic treatments with immunotherapy strategies, including ICI, CAR T cells and bispecific antibodies aim to impact both ECs and immune cells to block angiogenesis and at the same time to increase recruitment and activation of effector cells within the tumor.


Assuntos
Células Endoteliais , Neoplasias , Humanos , Células Endoteliais/metabolismo , Neoplasias/metabolismo , Linfócitos T , Citocinas/metabolismo , Neovascularização Patológica/metabolismo , Microambiente Tumoral
2.
Clin Case Rep ; 12(2): e8446, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38389963

RESUMO

Pyoderma gangrenosum is a rare inflammatory ulcerative skin disease of unknown etiology. We report an image of a patient with pyoderma gangrenosum who presented right leg ulcers with violaceous margins, histologically characterized by mono- and polynuclear cell infiltrates. The patient was successfully treated with cyclosporin A.

3.
Autoimmun Rev ; 23(4): 103514, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38181859

RESUMO

Pre-capillary pulmonary arterial hypertension (PAH) is hemodynamically characterized by a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary capillary wedge pressure (PAWP) ≤15 mmHg and pulmonary vascular resistance (PVR) > 2. PAH is classified in six clinical subgroups, including idiopathic PAH (IPAH) and PAH associated to connective tissue diseases (CTD-PAH), that will be the main object of this review. The aim is to compare these two PAH subgroups in terms of epidemiology, histological and pathogenic findings in an attempt to define disease-specific features, including autoimmunity, that may explain the heterogeneity of response to therapy between IPAH and CTD-PAH.


Assuntos
Autoimunidade , Doenças do Tecido Conjuntivo , Humanos , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/complicações , Hipertensão Arterial Pulmonar/imunologia , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Pulmonar/imunologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Hipertensão Pulmonar Primária Familiar/imunologia
4.
Lupus ; 32(13): 1528-1535, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37903488

RESUMO

Systemic lupus erythematosus (SLE) is a chronic and extremely disabling connective-tissue autoimmune disease with a tremendous impact on the quality of life (QoL). Belimumab, a B-lymphocyte-stimulator-specific inhibitor, is the first biologic drug approved as add-on therapy in patients with active, refractory auto-antibody-positive SLE.The impact of belimumab on the QoL of SLE patients was evaluated using a generic questionnaire short-form health survey 36 (SF-36) and the disease-specific questionnaire SLE-specific quality of life (SLEQoL).The Italian version of the SLEQoL and the SF-36 were administered to 46 SLE patients before and after 6 months of belimumab therapy. The control population consisted of 40 age-matched healthy individuals. The questionnaires were completed before and after belimumab treatment and the results were compared using the Wilcoxon signed-rank test. In addition, data from healthy controls and SLE patients were compared using the Mann-Whitney test. Dichotomous variables were compared using Fisher's exact test.For SLE patients, the addition of belimumab to their therapeutic regimen significantly improved their health-related QoL (HRQoL), according to the results of the SF-36 and SLEQoL. The comparison of the data obtained before and after belimumab treatment showed a decrease in all six SLEQoL domains and an increase in all eight SF-36 domains. Moreover, treatment led to a reduction in the median prednisone dose, to 0 mg/day (IQR 0-4.5 mg/day). Before belimumab therapy, SLE patients had a worse HRQoL than the control group, based on both questionnaires, but after belimumab treatment the outcome scores between SLE patients and controls were similar, suggesting that belimumab therapy resulted in a strong improvement in HRQoL. These findings were supported by a decrease in the SELENA-SLEDAI score, a measure of disease activity.In addition to clinical remission and low disease activity, the goals of an innovative therapeutic strategy for SLE should include the attainment of a good HRQoL. Our study demonstrates that the combined use of the SF-36 and SLEQoL questionnaires can provide clinicians with a better understanding of the HRQoL of SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico , Qualidade de Vida , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estudos de Coortes , Resultado do Tratamento , Índice de Gravidade de Doença
5.
Clin Immunol ; 255: 109740, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37586673

RESUMO

Anti-fibroblast antibodies (AFA) have been reported in systemic sclerosis (SSc) and are known to promote fibroblast activation. Aim of this study was to characterize the fine specificity of AFA and to analyze any correlations with clinical parameters associated to fibrosis. To this end, AFA were affinity-purified from a patient with diffuse cutaneous SSc (dcSSc) and interstitial lung disease (ILD). Panning of a phage display peptide library with purified AFA identified the motif . The peptide p121, bearing the AFA-specific motif, was used in ELISA to screen sera from 186 SSc patients and 81 healthy donors. Anti-p121 Ab serum levels were statistically higher in SSc than in healthy groups, and directly associated with dcSSc, reduced FVC (FVC < 70), and ILD. Given these clinical correlates, this study lays the groundwork for the identification of the antigen recognized by anti-p121 Ab, which might represent a novel therapeutic target for ILD.


Assuntos
Doenças Pulmonares Intersticiais , Esclerodermia Difusa , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/complicações , Fibroblastos , Ensaio de Imunoadsorção Enzimática , Pulmão
6.
Clin Exp Immunol ; 212(1): 32-38, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-36715304

RESUMO

Anti-centromere (ACA) and antimitochondrial antibodies (AMA) are specific for limited-cutaneous systemic sclerosis (lcSSc) and primary biliary cholangitis (PBC), respectively, and can coexist in up to 25 and 30% of SSc and PBC patients. Here, we evaluated whether anti-centromeric protein A (CENP-A) antibodies cross-react with mitochondrial antigens. To this end, sera from two lcSSc patients (pt1 and pt4), one of them (pt4) also affected by PBC, were used as the source of ACA, previously shown to recognize different groups of amino acids (motifs) in the CENP-A region spanning amino acids 1-17 (Ap1-17). Pt1 and pt4 Ap1-17-specific IgG were purified by affinity-chromatography on insolubilized Ap1-17-peptide column and tested by western blotting with nuclear and cytoplasmic protein extract from HeLa cells. Immunoreactive proteins were identified by mass spectrometry and validated by immunodot. The results showed that affinity-purified SSc/PBC pt4 anti-Ap1-17 and not SSc pt1 anti-Ap1-17 Ab, specifically cross-reacted with the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen in PBC. Sequence homology analysis indicated that the motif A-x-x-P-x-A-P recognized by pt4 anti-Ap1-17 IgG and shared by CENP-A and PDC-E2, is also expressed by some members of the Human Herpesvirus family, suggesting that they may trigger the production of these cross-reacting antibodies.


Assuntos
Cirrose Hepática Biliar , Escleroderma Sistêmico , Humanos , Autoanticorpos , Proteína Centromérica A , Complexo Piruvato Desidrogenase , Células HeLa , Autoantígenos , Imunoglobulina G , Aminoácidos , Especificidade de Anticorpos
7.
Biomolecules ; 12(8)2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-36008990

RESUMO

Irisin is an adipo-myokine, mainly synthetized in skeletal muscles and adipose tissues, that is involved in multiple processes. Only a few studies have evaluated serum irisin in psoriatic patients. This study aims to analyze serum irisin levels in patients with chronic plaque psoriasis, to compare them with values in controls, and to assess whether concentration of circulating irisin correlates with the severity of psoriasis, calculated by means of Psoriasis Area and Severity Index (PASI). We enrolled 46 patients with chronic plaque psoriasis; the control group included 46 sex- and age-matched subjects without any skin or systemic diseases. Serum irisin levels were measured by competitive enzyme linked immunosorbent assay. Our results showed a non-significant increase in serum irisin concentration in psoriatic patients compared to controls. A negative non-linear correlation between PASI and irisin levels was detected in psoriatic patients. Indeed, dividing patients according to psoriasis severity, the negative association between irisin and PASI was stronger in patients with mild psoriasis than in patients with higher PASI scores. Several control variables we tested showed no significant impact on serum irisin. However, erythrocyte sedimentation rate in the normal range was associated with significantly higher irisin levels in psoriatic patients. In conclusion, although irisin levels were not significantly different between controls and psoriatic patients, irisin was found to be negatively associated with psoriasis severity, especially in subjects with low PASI scores; however, further studies are needed to clarify the role of irisin in subjects with psoriasis.


Assuntos
Fibronectinas , Psoríase , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Índice de Gravidade de Doença
8.
Clin Exp Rheumatol ; 40(10): 1956-1963, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35579087

RESUMO

OBJECTIVES: In systemic sclerosis (SSc) patients, pulmonary arterial hypertension (PAH), which is preceded by pulmonary vascular disease (PVD), is one the of major causes of morbidity and mortality. Given the higher risk of PAH among anti-CENP antibodies (ACA)+ patients, we previously characterised a subset of ACA+ patients, based on a differential reactivity of their ACA with the phage clone (pc4.2)-expressing peptide 4.2 (p4.2). There was a considerably greater prevalence of a low diffusing lung capacity for carbon monoxide (DLCO), an expression of PVD, among patients with high anti-pc4.2 Ab levels. Here we examine whether a similar clinical subgroup can be identified within a larger cohort of ACA+ patients, using the synthetic p4.2. METHODS: Clinical data and serum samples were collected from 134 ACA+ patients. Sera were screened for reactivity with p4.2 by indirect ELISA. Statistical analyses were performed to define any associations between anti-p4.2 Ab levels and PVD. RESULTS: Kendall's analysis showed that anti-p4.2 Ab were directly associated with both a reduced DLCO and the presence of pulmonary fibrosis (PF). These associations were confirmed by Fisher's exact test. At multivariate analysis, anti-p4.2 Ab was associated to DLCO<70, DLCO≤60, and PF. Moreover, multivariable analysis showed that only the association of anti-p4.2 Ab with DLCO<70, and not with DLCO≤60, was independent of PF. CONCLUSIONS: Anti-p4.2 Ab are able to identify SSc patients at high risk of developing PVD even in the absence of PF. Patients with high anti-p4.2 Ab levels should be strictly monitored for PVD onset and eventually PAH.


Assuntos
Hipertensão Pulmonar , Fibrose Pulmonar , Escleroderma Sistêmico , Doenças Vasculares , Humanos , Monóxido de Carbono/metabolismo , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Biomarcadores , Doenças Vasculares/etiologia
9.
IDCases ; 26: e01331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840952

RESUMO

Among different pathogens, opportunistic viral infection caused by EBV is particularly relevant. This gammaherpesvirus, belonging to the Herpesviridae family, may complicate the disease course in different clinical settings by inducing pathological EBV pictures in patients with a defective immunologic response. Our report evaluated EBV-specific T cell responses by IFN- γ ELISPOT assay, which revealed defective EBV specific immunological response.

10.
J Clin Med ; 10(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34300172

RESUMO

Spondyloarthritis (SpA) is a group of inflammatory rheumatic diseases characterized by common clinical features, such as inflammatory enthesitis, arthritis and/or back pain. SpA is strongly associated with human leukocyte antigen (HLA) class I allotype B27. Ankylosing spondylitis has historically been the SpA subgroup with one of the strongest, best-proven associations with HLA-B27. The remaining SpA subgroups, namely psoriatic arthritis (PsA), inflammatory bowel diseases-associated arthritis/spondylitis, reactive arthritis, and undifferentiated SpA (uSpA), have also been associated with HLA allotypes other than HLA-B27. In this retrospective study, we analyzed the association between the HLA class I and II haplotypes and the susceptibility to enthesitis and/or arthritis (E/A). Special attention was paid to E/A responding to disease-modifying antirheumatic drugs (DMARDs) not fulfilling ASAS classification criteria (ASAS-), as compared to ASAS+ forms including PsA and uSpA. The whole E/A group showed significant independent associations with HLA-A28(68), B27, Cw3, Cw12, and DQ1; taken singly, PsA was associated with HLA-B27 and DQ1, uSpA with HLA-B16(38,39) and B27, and E/A ASAS- with HLA-A28(68), Cw8, and Cw12. This study identified novel risk HLA allotypes for different SpA subgroups in an Italian population. HLA typing could aid the diagnosis and treatment of E/A subgroups, including DMARDS-responsive forms not fulfilling ASAS classification criteria.

11.
Horm Mol Biol Clin Investig ; 42(3): 317-320, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675216

RESUMO

OBJECTIVES: Prader-Willi syndrome (PWS) is a rare genetic syndrome characterized by hyperphagia and early development of morbid obesity. Cardiovascular disease (CVD) and metabolic syndrome (MetS) are major comorbidities in these patients leading to premature death. Inhibitory factor 1 (IF1) works as a regulatory protein, inhibiting the ATP hydrolase activity of mitochondrial ATP synthase and likely playing a role in lipid metabolism. We aimed to assay IF1 in adult patients with PWS evaluating any relationship with clinical, genetic and biochemical parameters. METHODS: We recruited 35 adult patients with genetically confirmed PWS. RESULTS: IF1 serum concentration displayed a normal distribution with an average value of 70.7 ± 22.6 pg/mL, a median value of 66.1 pg/mL. It was above the reference range only in one patient. All parameters were compared from both sides of IF1 median without displaying any significant differences. Patients with normal or low HDL-cholesterol did not present any difference as regards IF1 levels, which were not different between patients with and without MetS. Non-esterified fatty acids (NEFA) serum levels (r=0.623; p<0.001) showed a statistically significant correlation with IF1. Cholesterol and its fractions did not present any correlation with IF1. CONCLUSIONS: In this study we do not confirm that HDL-cholesterol and IF1 are correlated, but we show that in adult PWS patients, NEFA are correlated with serum IF1. This protein could play a role to some extent in determining the complex metabolic alterations in PWS patients.


Assuntos
Biomarcadores/sangue , Síndrome de Prader-Willi/sangue , Proteínas/metabolismo , Adulto , Predisposição Genética para Doença , Humanos , Metabolismo dos Lipídeos , Lipídeos/sangue , Masculino , Fenótipo , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Proteína Inibidora de ATPase
12.
Autoimmun Rev ; 20(3): 102750, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33482338

RESUMO

The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is an important intracellular route through which many different extracellular soluble molecules, by reaching membrane receptors, can signal the nucleus. The spectrum of soluble molecules that use the JAK/STAT pathway through their corresponding receptors is quite large (almost 50 different molecules), and includes some cytokines involved in the pathogenesis of many immune-mediated diseases. Such diseases, when left untreated, present an evident hyperactivation of JAK/STAT signaling. Therefore, given the pathogenetic role of JAK/STAT, drugs known as JAK inhibitors (JAKi), that target one or more JAKs, have been developed to counteract JAK/STAT signal hyperactivation. As some hematological malignancies present an intrinsic JAK/STAT hyperactivation due to a JAK mutation, some JAKi have also been successfully used in this context. Regulatory agencies for drug administration in different countries have already approved a few JAKi in the setting of either immune-mediated diseases or hematological malignancies. Aim of this review is to describe the physiology of intracellular JAK/STAT pathway signaling and the pathological conditions associated to its dysregulation. Then, the rationale for targeting JAK in rheumatic autoimmune diseases is discussed, along with clinical data from registration studies showing the efficacy of these drugs. Finally, the excellent safety profile of JAKi is discussed in the context of the apparent poor specificity of JAK/STAT pathway signal.


Assuntos
Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Transdutores
14.
Ital J Pediatr ; 46(1): 161, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115520

RESUMO

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol biosynthesis with accumulation of 7-dehydrocholesterol. Inhibitory factor 1 (IF1) is a well-known mitochondrial protein. Recently, it has been discovered in the human serum where it is reported to be involved in the HDL-cholesterol intake. Here we report the IF1 presence in the serum of two paediatric SLOS dizygotic twins treated with dietary cholesterol supplementation. CASE PRESENTATION: The patients showed a typical phenotype. They started dietary supplementation with cholesterol when 2 months old. The cholesterol intake was periodically titrated on the basis of weight increase and the twin 1 required a larger supplementation than the twin 2 during the follow-up. When 6.4-year-old, they underwent IF1 assay that was 7-fold increased in twin 2 compared to twin 1 (93.0 pg/ml vs 13.0 pg/ml, respectively). CONCLUSIONS: We report, for the first time, the presence of circulating IF1 in the serum of SLOS patients, showing different levels among them. Our findings confirm that IF1 could be a novel research target in cholesterol-related disorders and also in SLOS, and could contribute to the general debate on IF1 as a new modulator of cholesterol levels.


Assuntos
Colesterol na Dieta/administração & dosagem , Proteínas/metabolismo , Síndrome de Smith-Lemli-Opitz/dietoterapia , Síndrome de Smith-Lemli-Opitz/enzimologia , Gêmeos Dizigóticos , Feminino , Humanos , Lactente , Masculino , Proteína Inibidora de ATPase
16.
Int J Mol Sci ; 21(9)2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32397684

RESUMO

The current pandemic coronavirus, SARS-CoV-2, is a global health emergency because of its highly contagious nature, the great number of patients requiring intensive care therapy, and the high fatality rate. In the absence of specific antiviral drugs, passive prophylaxis, or a vaccine, the treatment aim in these patients is to prevent the potent virus-induced inflammatory stimuli from leading to the acute respiratory distress syndrome (ARDS), which has a severe prognosis. Here, the mechanism of action and the rationale for employing immunological strategies, which range from traditional chemically synthesized drugs, anti-cytokine antibodies, human immunoglobulin for intravenous use, to vaccines, are reviewed.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/terapia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/terapia , Pandemias , Pneumonia Viral/patologia , SARS-CoV-2
17.
Int J Mol Sci ; 20(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003532

RESUMO

Antigen-mimicking peptide (mimotope)-based vaccines are one of the most promising forms of active-immunotherapy. The main drawback of this approach is that it induces antibodies that react poorly with the nominal antigen. The aim of this study was to investigate the molecular basis underlying the weak antibody response induced against the naïve protein after peptide vaccination. For this purpose, we analyzed the fine specificity of monoclonal antibodies (mAb) elicited with a 13-mer linear peptide, complementary to theantigen-combining site of the anti-CD20 mAb, Rituximab, in BALB/c mice. Anti-peptide mAb competed with Rituximab for peptide binding. Even so, they recognized a different antigenic motif from the one recognized by Rituximab. This explains their lack of reactivity with membrane (naïve) CD20. These data indicate that even on a short peptide the immunogenic and antigenic motifs may be different. These findings highlight an additional mechanism for epitope spreading and should be taken into account when designing peptides for vaccine purposes.


Assuntos
Anticorpos Monoclonais/genética , Antígenos CD20/imunologia , Peptídeos/genética , Rituximab/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos/genética , Anticorpos Monoclonais Murinos/imunologia , Antígenos CD20/genética , Sítios de Ligação de Anticorpos/genética , Epitopos/genética , Epitopos/imunologia , Humanos , Camundongos , Biblioteca de Peptídeos , Peptídeos/imunologia , Rituximab/genética , Vacinação/métodos , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia
18.
Open Access Rheumatol ; 10: 129-134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233261

RESUMO

BACKGROUND AND OBJECTIVE: Anti-carbamylated protein antibodies (anti-CarP Ab) represent a novel kind of autoantibodies specificity detectable in the sera of patients with rheumatoid arthritis (RA). They have been recently reported to be associated with increased mortality in Spanish patients with RA. The aim of our study was to compare the incidence mortality rates (IMRs) detected in RA patients from a tertiary Italian center with those reported in other European tertiary centers and to evaluate the putative role of anti-CarP Ab in modulating the low IMR detected in our patients. METHODS: Clinical charts of patients consecutively admitted to our center, from January 1, 2008, to December 31, 2014, were retrospectively reviewed. The mortality rate (expressed as the number of deaths in the cohort divided by the number of years of IMR follow-up) and causes of death were assessed at December 31, 2015. Sera of 61 patients, representative of the whole cohort, collected at the time of admission to our center were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab in our series were compared with those reported in other European cohorts. RESULTS: We observed 608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy and the Spanish cohort, while only all-cause and cardiovascular IMRs were significantly lower in our series with respect to the Leiden Early Arthritis Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than in any other European cohorts. CONCLUSION: We confirm that the mortality rate is lower in our Italian RA cohort with respect to other European cohorts. Whether the low prevalence of anti-CarP Ab might be responsible for this result awaits to be furtherly investigated.

19.
Autoimmun Rev ; 17(4): 366-375, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29425936

RESUMO

Atherosclerotic vasculopathy is a multifactorial process causing vessels damage and cardiovascular diseases, the leading causes of death worldwide. Atherosclerotic plaque is the asymptomatic primary, elementary, lesion of atherosclerotic vasculopathy. Accumulation of the oxidized low-density lipoprotein (oxLDL) at sub endothelial sites is now recognized as one of the major trigger events in plaque formation. The concomitant presence at the plaque site of cells belonging to either natural or adaptive immunity, the detection of autoantibodies to oxLDL, the cross-reactivity of oxLDL with anti-phospholipid antibodies, in addition to the clinical evidence of increased rates of cardiovascular events in several rheumatic diseases, has stimulated intensive research to define interconnections between the immune system and traditional risk factors at the molecular levels in order to explain accelerated atherosclerosis. Here, we critically review the results of previous and recent studies, which have disclosed molecules of both innate or adaptive immunity involved in atherosclerosis, focusing primarily on B cells and autoantibodies, where data are more consolidated. Particular attention has also been paid to molecules that may be predictive markers of atherosclerosis progression and can be potential targets for immune intervention to delay the atherosclerotic process. The latter include CD20 antigen, molecules involved in the BAFF-BAFF receptor axis, inflammatory molecules and modified LDL. The successful results of a recent randomized controlled clinical trial targeting inflammasome with anti-IL1ß monoclonal antibody in non-autoimmune conditions, prove that specific immunotherapy can be a promising and effective strategy to control atherosclerosis in rheumatic diseases as well.


Assuntos
Aterosclerose/imunologia , Autoimunidade/imunologia , Lipoproteínas LDL/imunologia , Doenças Reumáticas/imunologia , Animais , Aterosclerose/complicações , Humanos , Lipoproteínas LDL/metabolismo , Doenças Reumáticas/complicações , Fatores de Risco
20.
PLoS One ; 13(12): e0210023, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30596753

RESUMO

Carbamylation is a post-translational modification that mostly affects proteins with low turnover, such as dermal proteins. Carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alterations. As dermis is affected by systemic sclerosis (SSc) and anti-carbamylated protein antibodies (anti-CarP Ab) are found in SSc patients, we sought to evaluate the specificity of anti-CarP Ab and their relationship with clinical parameters reflecting skin involvement in SSc. This study investigated serum samples and clinical data from 124 patients with SSc. Anti-CarP Ab were affinity purified from pooled SSc sera, and their specificity was assessed by western blotting and ELISA with carbamylated proteins from two species (human and bovine albumin; human fibrinogen). Anti-CarP Ab were measured in SSc serum samples and in 41 healthy aged-matched individuals. Affinity-purified anti-CarP Ab recognized carbamylated epitopes irrespective of the protein type or species origin. Anti-CarP Ab levels inversely correlated with the modified Rodnan skin score (mRss) (Spearman's R = -0.32, p<0.001), independently of patients' age. Receiver operating characteristics (ROC) analysis identified anti-CarP Ab cut-offs that best discriminated dichotomized clinical variables related to skin involvement: the only clinical variables that were significantly different between groups were mRss (p = 0.001) and scleredema (p<0.001). Low anti-CarP Ab levels were associated with worse skin involvement. Future prospective studies are needed to assess their usefulness in the clinical setting.


Assuntos
Autoanticorpos/sangue , Carbamilação de Proteínas , Escleroderma Sistêmico/sangue , Pele/metabolismo , Adulto , Animais , Bovinos , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia , Pele/patologia
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