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CD21low B cells have recently been found increased in SSc-associated digital ulcers (DUs) or interstitial lung disease (ILD). To further characterize CD21low B cells which encompass autoreactive cells, we analyzed their expression of the inhibitory CD32 receptor in SSc. Peripheral blood mononuclear cells from 27 patients with SSc and 15 age-and sex-matched healthy controls (HCs) were analyzed with multicolor flow cytometry. CD21low B cells were significantly increased in patients with DUs (51.3%) compared to HCs (28.1%) and in patients with ILD (53.1%) compared to HCs. CD21lowCD32low B cells were significantly increased in patients with DUs (23.8%) compared to HCs (4.4%), in patients with ILD (28.4%) compared to HCs, and in anti-topoisomerase I (+) patients (21.5%) compared to HCs and to anti-topoisomerase I (-) patients (2.4%). Autoreactive B cells recognizing Topoisomerase I were predominantly within CD32low cell fraction. Our study further supports the autoreactive status of CD21lowCD32low B cells in SSc patients.
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DNA Topoisomerases Tipo I , Doenças Pulmonares Intersticiais , Proteínas Nucleares , Escleroderma Sistêmico , Úlcera Cutânea , Humanos , Leucócitos MononuclearesRESUMO
Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disorder with multifaceted clinical findings in different organ systems. Neuropsychiatric manifestations affect more than half of SLE patients, and there is increasing evidence that anorexia nervosa (AN), a feeding and eating disorder (FED) characterized by significantly reduced energy intake, is among them. Herein, a review of the literature on the potential association between jSLE and AN was performed. Reported clinical cases were identified, and putative pathophysiological mechanisms were sought that could potentially explain the observed relationship between these two pathological entities. Four reports of isolated cases and a case series including seven patients were identified. In this limited patient pool, the diagnosis of AN preceded that of SLE in the majority of cases, whereas in all cases both entities were diagnosed within a time span of two years. Many explanations for the observed relationships have been proposed. AN has been associated with the stress of chronic disease diagnosis; on the other hand, the chronic inflammation associated with AN may contribute to the development/appearance of SLE. Adverse childhood experiences, concentrations of leptin, shared autoantibodies, and genetic traits appear to be important factors in this well-established interplay. In essence, it seems important to increase clinician awareness of the concomitant development of AN and SLE and invite further research on the subject.
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Several cases of vaccine-associated manifestations have been published including cases of inflammatory myositis. Herein, we comprehensively review the literature on the occasion of case of a woman with inflammatory myositis following COVID-19 vaccination. A 67-year-old woman presented with left arm edema, rash, and weakness after the 2nd dose of the BTN162b2 vaccine. Raised muscle enzymes and inflammatory markers with muscle edema on MRI and myositis findings on the electromyogram established the diagnosis. She was successfully treated with methylprednisolone pulses, intravenous immunoglobulin, methotrexate, and hydroxychloroquine. Cases of inflammatory myositis, dermatomyositis, or interstitial lung disease with myositis-specific autoantibodies or myositis-associated autoantibodies within 12 weeks from SARS-CoV-2 vaccination were included. Cases with malignancy, prior or subsequent COVID-19 infection, preexisting myositis/interstitial lung disease (ILD)/dermatomyositis (DM), or other connective tissue diseases were excluded. From our search, 49 cases were identified (mean age: 56.55 + 17.17 years), 59% were women, while 12 patients received the ChAdOx1 vaccine, 27 the BNT162b2, 8 the mRNA-1273, 1 the DB15806, and 1 the Ad26.COV2.S (overall, 70% received mRNA vaccines). Muscle involvement was the most common manifestation (79.5%), followed by skin involvement (53%) and ILD (34.6%), which were more common in the m-RNA vaccinees. Muscle biopsy, MRI findings, and autoantibody profile varied significantly, while successful immunosuppressive treatment was applied in most cases. Inflammatory myositis after COVID-19 vaccination has been well documented worldwide. Current evidence in support of a pathogenic link is challenging due to significant variation in clinical manifestations, radiological, histopathological, and immunological features.
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Vacinas contra COVID-19 , COVID-19 , Dermatomiosite , Doenças Pulmonares Intersticiais , Miosite , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ad26COVS1 , Autoanticorpos , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Dermatomiosite/diagnóstico , Miosite/induzido quimicamente , Miosite/diagnóstico , SARS-CoV-2RESUMO
The pathogenesis of SSc is incompletely understood, but several lines of evidence suggest that B cells are involved. Effector B (Beff) cells are hyperactivated and produce autoantibodies (autoAbs), and regulatory B cells (Bregs) are decreased, although a recent study reported a defect in central B cell tolerance. AutoAbs appear before fibrosis, and some have direct profibrotic effects, while others also induce microvasculopathy. Recently, a study found that B cells reactive to topo I with high affinity produce IL-6 and cause fibrosis in mice, whereas B cells with low affinity for topo I produce IL-10 and inhibit fibrosis. Ibrutinib, a Bruton's tyrosine kinase inhibitor, promoted B cells with low affinity for topo I and decreased fibrosis. These findings provide a rationale for innovative B cell-directed strategies for managing SSc, such as ibrutinib or chimeric antigen receptor T cells, particularly in the early inflammatory stage of the disease.
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Linfócitos B Reguladores , Escleroderma Sistêmico , Animais , Camundongos , Autoanticorpos , FibroseRESUMO
Hip synovial cysts are rare. However, in patients with Rheumatoid Arthritis (RA) they present in higher frequency than in general population. Herein, we present an unusual case of a 67-year-old man with RA that presented with unilateral leg oedema and Deep Vein Thrombosis (DVT). Computed tomography (CT) scan revealed a giant cystic lesion adjacent to the right hip joint with longitudinal diameter of 14 cm. Magnetic Resonance Imaging (MRI) confirmed the characteristics of the cyst. Interestingly enough, there was evidence of osteonecrosis of the femoral head. CT guided Fine Needle aspiration (FNA) of the fluid revealed fluid consistency similar to synovial fluid, while it excluded infectious process and malignancy. Patient was finally treated with total hip arthroplasty 3 months after the initiation of low molecular weight heparin (LMWH) in treatment dose.
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OBJECTIVE: To assess the possible impact conferred by co-existing variants in MEditerranean FeVer (MEFV) and other genes on systemic autoinflammatory disease (SAID) phenotype. METHODS: Consecutive patients (n = 42) who underwent screening for SAIDs by next generation sequencing (NGS) targeting 26 genes, and carried at least one MEFV gene variant, were retrospectively studied. A total of 63 MEFV gene variants mainly located in exon 10 (n = 29) and exon 2 (n = 19) were identified in 21 patients with juvenile- and 21 with adult-onset disease. RESULTS: The candidate clinical diagnosis was Familial Mediterranean Fever (FMF) in 11, polygenic SAIDs (PFAPA, Still's disease, atypical SAPHO and inflammatory bowel disease) in 9, whereas the disease could not be clinically defined in 22 patients. Notably, 33 out of the 42 patients (79%) had at least one co-existing variants in 19 genes other than MEFV. NGS confirmed all clinical diagnoses and helped defining diagnosis in 59% of the remaining cases. Patients with undefined SAIDs (n = 9) or atypical FMF phenotype (n = 12) carried significantly more disease-causing variants in genes other than MEFV compared to patients with typical FMF (n = 9). More than one variants in these genes were significantly associated with adult-onset disease, while disease-causing variants in the same genes were also associated with an overall more severe SAID phenotype. CONCLUSION: Co-existing variants in SAID-related genes may explain the phenotypic variability of these diseases. Further studies should validate combined molecular and clinical data in order to better understand the cumulative gene dosage effect and improve the classification of these patients.
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Doenças Autoimunes , Dosagem de Genes , Pirina , Doenças Autoimunes/genética , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Humanos , Mutação , Pirina/genética , Estudos RetrospectivosRESUMO
Introduction: Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort. Materials and methods: Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later. Results: One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58-59.85), history of cancer (OR = 2.35, 95% CI: 1.09-5.06), bDMARD use (OR = 1.85, 95% CI: 1.29-2.65), seropositivity (OR = 1.47, 95% CI: 1.05-2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17-1.51). Male sex (OR = 0.65, 95% CI: 0.43-0.99) was a negative predictor for pneumococcal vaccination during follow-up. Discussion: Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a "vaccination culture" in RA patients.
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Introduction: Limited data from clinical trials in multiple sclerosis (MS) reported that minocycline, a widely used antibiotic belonging to the family of tetracyclines (TCs), exerts a beneficial short-lived clinical effect A similar anti-inflammatory effect of minocycline attributed to a deviation from Th1 to Th2 immune response has been reported in experimental models of MS. Whether such an immunomodulatory mechanism is operated in the human disease remains largely unknown. Aim: To assess the in vitro immunomodulatory effect of tetracyclines, and in particular minocycline and doxycycline, in naïve and treated patients with MS. Material and Methods: Peripheral blood mononuclear cells from 45 individuals (35 MS patients, amongst which 15 naïve patients and 10 healthy controls, HCs) were cultured with minocycline or doxycycline and conventional stimulants (PMA/Ionomycin or IL-12/IL-18). IFN-γ and IL-17 producing T-, NK- and NKT cells were assessed by flow cytometry. The effect of TCs on cell viability and apoptosis was further assessed by flow cytometry with Annexin V staining. Results: Both tetracyclines significantly decreased, in a dose dependent manner, IFN-γ production in NKT and CD4+ T lymphocytes from MS patients (naïve or treated) stimulated with IL-12/IL-18 but did not decrease IFN-γ producing CD8+ T cells from naive MS or treated RRMS patients. They also decreased IL-17+ T and NKT cells following PMA and Ionomycin-stimulation. Tetracyclines did not affect the viability of cell subsets. Conclusion: Tetracyclines can in vitro suppress IFN-γ and IL-17- producing cells from MS patients, and this may explain their potential therapeutic effect in vivo.
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Imunidade Adaptativa/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Esclerose Múltipla Crônica Progressiva/imunologia , Tetraciclinas/farmacologia , Imunidade Adaptativa/imunologia , Adulto , Feminino , Humanos , Imunidade Inata/imunologia , Interferon gama/biossíntese , Interleucina-17/biossíntese , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Evidence on comorbidity prevalence in antiphospholipid syndrome (APS) and its difference from high comorbidity burden rheumatic diseases is limited. Herein, we compare multiple comorbidities between APS and RA. METHODS: A total of 326 patients from the Greek APS registry [237 women, mean age 48.7 (13.4) years, 161 primary APS (PAPS), 165 SLE-APS] were age/sex matched (1:2 ratio) with 652 patients from a Greek multicentre RA cohort of 3115 patients. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA patients using multivariate regression analysis. RESULTS: Ηyperlipidemia and obesity (ΒΜΙ ≥ 30 kg/m2) were comparable while hypertension, smoking, stroke and CAD were more prevalent in APS compared with RA patients. Osteoporosis and depression were more frequent in APS, while DM, COPD and neoplasms did not differ between the two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in both PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more frequent only in SLE-APS vs RA, whereas DM was less prevalent in PAPS vs RA. Hyperlipidaemia was independently associated with CV events (combined stroke and CAD) in PAPS and SLE-APS, while CS duration was associated with osteoporosis in SLE-APS. CONCLUSION: Comorbidity burden in APS (PAPS and SLE-APS) is comparable or higher than that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and CS exposure minimization.
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Síndrome Antifosfolipídica/epidemiologia , Artrite Reumatoide/epidemiologia , Fatores de Risco de Doenças Cardíacas , Estudos de Casos e Controles , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Grécia/epidemiologia , Humanos , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Obesidade/epidemiologia , Osteoporose/epidemiologia , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Análise de Regressão , Fatores de Risco , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
Anti-Ro52 autoantibody (autoAb), highly prevalent in Sjogren's syndrome (SjS) and systemic lupus erythematosus (SLE), is also frequent in systemic sclerosis (SSc). Viral agents, such as human cytomegalovirus (HCMV), have been considered as a trigger for SSc and SSc-associated autoAbs. To seek for antigen-specific anti-HCMV associations with anti-Ro52, we assessed the dominant anti-HCMV ab responses in anti-Ro52 antibody (ab)-positive and -negative patients with SSc and compared them with those in SLE and SjS. 116 Anti-HCMV ab(+) sera were analyzed, including 70 from anti-Ro52(+) patients (29 SSc, 23 SLE and 18 SjS) and 46 from anti-Ro52(-) patients (29 with SSc, 9 with SLE and 8 with SjS) as negative controls. Abs against specific HCMV pp130/UL57, pp65/UL83, pp55/UL55, pp52/UL44, p38 and pp28/UL99 antigens were tested by immunoblotting. Anti-Ro52(+) SSc patients reacted more frequently against pp52/UL44 and p38 compared to anti-Ro52(-) [(13/29, 44.8%; 95% CI 26.7-62.9% vs. 1/29, 3.4%; 95% CI 0-10%, p < 0.001, and 9/29, 31.0%; 95% CI 14.2-47.8% vs. 2/29, 6.9%; 95% CI 0-16.1%, p = 0.041, respectively]. No such differences were noted between anti-Ro52(+) and anti-Ro52(-) SLE or SjS patients. Also, antibody titres against HCMV pp65/UL83, pp52/UL44 and p38 antigens were higher in anti-Ro52(+) than anti-Ro52(-) SSc patients (p < 0.01). Ab responses against specific HCMV antigens differ among anti-Ro52 ab-positive and -negative patients with SSc (as well as between SSc and SLE or SjS), but whether these differences are epiphenomenal remains to be seen.
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Autoanticorpos/sangue , Escleroderma Sistêmico/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Ribonucleoproteínas/sangue , Ribonucleoproteínas/imunologia , Escleroderma Sistêmico/sangue , Síndrome de Sjogren/sangue , Síndrome de Sjogren/imunologiaRESUMO
Anti-nuclear antibodies (ANA) are frequently detected in patients with psoriasis (Ps) and psoriatic arthritis (PsA), but their target autoantigens remain unknown. We assessed antibody (ab) reactivity against 23 known nuclear antigens in patients with Ps and PsA and assess the effects of secukinumab (anti-IL17A) treatment on ANA levels. A total of 201 patients, 101 with Ps and 100 with PsA, and 50 ANA-negative healthy controls (HCs) were tested for ANAs by a line immunoassay testing reactivity to 23 nuclear antigens. Ab reactivity to at least 1 antigen was found in 20.4% psoriatic disease patients (25.7% Ps and 15% PsA) compared to 8% HCs (p = ns), the most frequent being against dense fine speckled 70 (DFS70) (6.5%). In Ps and PsA patients with secukinumab-induced remission, anti-DFS70 and other antigen-specific autoantibodies were diminished over time. No decline was noted for IgG abs against antigens from pathogens such as cytomegalovirus, Epstein-Barr virus and Helicobacter pylori. Autoantibody decrease was associated with significant reduction of plasmablasts, follicular B and follicular T cells. In conclusion, one third of antigen-specific ANA patients with psoriatic disease recognize DFS70. Secukinumab decreases nuclear antigen autoreactivity, plasmablasts, follicular B and follicular T cells, highlighting a new mechanism of its action.
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Autoanticorpos , Infecções por Vírus Epstein-Barr , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Anticorpos Antinucleares , Anticorpos Monoclonais Humanizados , Antígenos Nucleares , Técnica Indireta de Fluorescência para Anticorpo , Herpesvirus Humano 4 , Humanos , Fatores de Transcrição/metabolismoRESUMO
miRNAs are small non-coding RNA molecules that participate through silencing in post-transcriptional regulation of gene expression. Recent studies have highlighted the importance of microRNAs (miRNAs) as regulators of both the innate and the adaptive immune response. There are emerging data regarding the role of miRNAs in patients with Systemic Lupus Erythematosus (SLE). One of the main stimuli for the induction of miR-21 is hypoxia. Moreover, the expression and function of miR-210 is directly related to the activity of "hypoxia inducible factor-1a" (HIF-1a). The aim of the study is to examine the regulation of miR-21 and mir-210 in patients with SLE based on the hypothesis that cellular hypoxia may have an important role in SLE pathogenesis. Plasma, PBMC and urine samples will be collected from patients with SLE and normal controls. miR expression will be studied with real-time PCR. Functional experiments will examine the effect of miR-21 and miR- 210 on HIFa and ERK1/2 και PI3K/AKT signalling pathways. The study will provide novel data regarding the expression and the role of miR-21 and miR-210 in patients with SLE. The results of the study will contribute to a better understanding of miR network regulation in SLE in order to ultimately identify molecules that can be used in clinical practice as diagnostic or prognostic markers, treatment response markers, or even as potential future therapeutic targets.
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Reactivation of viruses occurs in autoimmune disorders in the setting of certain immunosuppressive drugs. We describe a 54-year-old female with systemic sclerosis and extensive cutaneous calcinosis who had been treated with methotrexate for 18 months and presented with headache and neurological deficits. She was diagnosed with progressive multifocal leukoencephalopathy, a rare disease caused by JC virus. Methotrexate was discontinued and mirtazapine plus mefloquine were added. The patient showed a slow recovery and five years later she had complete resolution of progressive multifocal leukoencephalopathy clinical manifestations. Calcinosis had a limited response to various agents and severely affected daily activities of the patient. This case report, highlights the importance of clinical suspicion for progressive multifocal leukoencephalopathy in every patient with immune-mediated disease, even on weak immunosuppressant, who presents with central nervous system manifestations and also the unmet therapeutic need for systemic sclerosis-associated calcinosis.
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OBJECTIVES: Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL-10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. METHODS: Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. RESULTS: Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. CONCLUSION: These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.
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Artrite Psoriásica/tratamento farmacológico , Linfócitos B Reguladores/patologia , Imunidade Inata/efeitos dos fármacos , Interleucina-10/biossíntese , Psoríase/tratamento farmacológico , Linfócitos T/patologia , Talidomida/análogos & derivados , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/imunologia , Artrite Psoriásica/metabolismo , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/imunologia , Biomarcadores/metabolismo , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Psoríase/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Talidomida/uso terapêuticoRESUMO
Anti-synthetase syndrome is an autoimmune disorder characterized by the presence of autoantibodies against aminoacyl transfer RNA (tRNA) synthetases, and myositis, interstitial lung disease (ILD), arthritis, fever and Raynaud's phenomenon (RP). We present a 54-year-old woman, who complained of fatigue, low-grade fever, myalgias, arthralgias, RP and dyspnoea on exertion. Chest CT scan revealed features of interstitial lung disease. Due to rapid deterioration of her lung function, she required oxygen support. The patient did not respond to empiric treatment with antibiotics. Autoantibody testing was remarkable for ANA positivity (1/160) and high-titre anti-Jo1 positivity. A diagnosis of anti-synthetase syndrome was made and the patient was placed on high-dose corticosteroids and rituximab with significant improvement. At 1-year follow up, she remains in good condition, without the need for oxygen supplementation.
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Epitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed. The aim of the present study was to fully characterize Ro52 epitopes in anti-Ro52-positive SSc using Ro52 fragments spanning the full antigen. Further analysis was made according to anti-Ro60 status. Epitope mapping was performed in 43 anti-Ro52-positive SSc patients. Seventy eight anti-Ro52-positive pathological controls, including 20 patients with SjS, 28 patients with SLE, 15 patients with dermatomyositis (DM), and 15 patients with primary biliary cholangitis (PBC), and 20 anti-Ro52-negative healthy individuals as normal controls were also tested. Five recombinant Ro52 fragments [Ro52-1 (aa 1-127), Ro52-2 (aa 125-268), Ro52-3 (aa 268-475), Ro52-4 (aa 57-180), and Ro52-5 (aa 181-320) were used to test reactivity by line-immunoassay and in house ELISA. Anti-Ro60 reactivity was tested by ELISA. All anti-Ro52 positive sera reacted with Ro52-2; none recognized Ro52-3. Antibodies against Ro52-1 were less frequently found in SSc than in SjS/SLE (11.6 vs. 41.7%, p = 0.001); and antibodies against Ro52-4 were less frequently found in SSc than in SjS/SLE (27.9 vs. 50%, p = 0.03). In SSc patients, reactivity against Ro52-1 was more frequent in anti-Ro52+/anti-Ro60+ than in anti-Ro52+/anti-Ro60-patients (33.3 vs. 0%, p = 0.003). In this comprehensive analysis of Ro52 epitope mapping in SSc, the coiled coil domain remains the predominant epitope on Ro52. Contrary to SjS and SLE, patients with SSc fail to identify epitopic regions within the N-terminus of the protein, especially if they lack con-current anti-Ro60 reactivity.
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Autoanticorpos/imunologia , Autoantígenos/imunologia , Mapeamento de Epitopos , Epitopos/imunologia , RNA Citoplasmático Pequeno/imunologia , Ribonucleoproteínas/imunologia , Escleroderma Sistêmico/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Domínios Proteicos , Escleroderma Sistêmico/patologiaRESUMO
Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, immune activation, and extensive collagen deposition. Microvasculopathy and immune activation occur very early in the disease process. Evidence from animal models and in vitro studies indicate that T-cells and B-cells activate fibroblasts to produce collagen. Traditional immunosuppressants, cyclophosphamide(CyP), methotrexate(MTX), and more recently mycophenolate mofetil(MMF), may prove more effective if used very early in the disease course. These drugs showed some benefit in skin (MTX, CyP, MMF) and lung function (CyP, MMF). Biologicals, such as intravenous immunoglobulin (IVIg), belimumab(Beli), tocilizumab(TCZ), abatacept(Aba), rituximab(RTX) and fresolimumab(Fresu) appear promising as they exhibited some benefit in skin (IVIg, Beli, TCZ, Aba, RTX, Fresu), hand function (IVIg), and joints (IVIg, TCZ, Aba). Autologous stem cell transplantation showed the best therapeutic efficacy on skin and internal organs, and looks very promising, as modification of transplantation immunosuppression is decreasing the early high mortality.
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We propose curcumin as a preventive measure to avoid/manage periodontitis (PD), and as a natural immunosuppressant for rheumatoid arthritis (RA). PD, mainly caused by Porphyromonas gingivalis forming biofilm and leading to tooth decay, is a major public health issue and a risk factor for the development of RA in humans. P. gingivalis is able to trigger experimental autoimmune arthritis in animal models and in humans can induce citrullinated peptides, which not only are a source of anti-citrullinated antibodies (ACPAs), but also participate in autoreactive responses and disease development. Curcumin appears to have efficient anti-bacterial activity against P. gingivalis infection and biofilm formation. In addition to antibacterial, anti-oxidant, and anti-inflammatory action, curcumin exerts unique immunosuppressant properties via the inhibition of Th17 pro-inflammatory responses and promotion of regulatory T cells, thus suppressing autoimmunity. We introduce curcumin as a natural product for the management of both PD and RA-related autoreactivity, possibly also as a preventive measure in early RA or individuals at high risk to develop RA.
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Antibacterianos/uso terapêutico , Anticorpos Antiproteína Citrulinada/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Curcumina , Imunossupressores/uso terapêutico , Periodontite/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Porphyromonas gingivalis/efeitos dos fármacos , Animais , Antibacterianos/isolamento & purificação , Anticorpos Antiproteína Citrulinada/sangue , Antirreumáticos/isolamento & purificação , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Curcumina/química , Modelos Animais de Doenças , Humanos , Imunossupressores/isolamento & purificação , Periodontite/imunologia , Periodontite/microbiologia , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/patogenicidade , Fatores de Risco , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologiaRESUMO
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune rheumatic disease characterized by a wide range of disease-specific and disease-related autoantibodies (autoAbs). Profile assays have been developed and are currently in use to meet the demand for better characterization of all autoAbs found in SSc patients. AIM: To assess the clinical relevance of SSc-related autoantibodies in 158 patients with SSc, all from Central Greece, taking advantage of a multiparametric SSc autoantibody line immunoassay. MATERIAL AND METHODS: 158 consecutive patients with SSc (137 females, mean age 53.2 ± 10 years; 63 patients with dcSSc and 95 with lcSSc) from central Greece were included in the study. Eighteen patients with morphea were also included. Serum samples were analyzed by a profile SSc nucleoli line assay (Euroimmun) to detect Abs against 13 autoantigens: Scl-70, Centromere (A, B), RNA polymerase III (subunits 11 & 155), fibrillarin, NOR90, Th/To, PM/Scl 100, PM/Scl75, Ku, PDGFR and Ro52. Antinuclear autoAbs (ANAs) were detected by indirect immunofluorescence. RESULTS: ANAs were detected in 97.5% of SSc patients. Reactivities to specific autoantigens were as follows: Topo I, 40.5%; CENP, 32.9%; Ro52, 21.5%; RP11, 8.9%; RP155, 13.3%; NOR 90, 4.4%; Ku 3.8%; PM-Scl75, 3.2%; PM-Scl100, 1.3%; Th/To, 1.3%; Fibrillarin, 1.3%; PDGFR 0%; Ro52 21.5%. Twenty-one of SSc did not have any of the main autoAbs, namely anti-Topo I, anti-CENP, anti-RNA pol III Abs. CONCLUSIONS: Multiparametric autoAb test provides positive SSc-associated autoAb reactivities in SSc patients negative for the three main autoAbs and this may prove of significance in early disease diagnosis.
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Our aim was to study CD19(+)CD27(+)CD24(high) memory and CD19(+)CD24(high)CD38(high) transitional and IL-10+Breg cells, known to inhibit Th1 and Th17 cells in experimental arthritis, in psoriatic arthritis (PsA) and psoriasis (Ps). Peripheral blood Breg cells from 60 patients with PsA, 50 patients with Ps and 23 healthy controls were analyzed by flow cytometry. IL-17A-producing CD3(+) T cells and IFNγ-producing CD3(+) T cells and activation of p38 MAPK and STAT3 were also studied. CD19(+)CD27(+)CD24(high) and CD19(+)CD24(high)CD38(high) Breg cells were decreased in PsA and Ps. In Ps patients, CD19(+)CD27(+)CD24(high) Breg cells inversely correlated with PASI score. IL-10+Bcells were also decreased and inversely correlated with IL-17A+CD3+ and IFN-γ+CD3+ T cells. B cells from patients exhibited impaired activation of p38 MAPK and STAT3. In conclusion, IL-10+Breg cells are decreased PsA and Ps and inversely correlated with the severity of psoriasis and IL-17A+ and IFNγ+ T cells.