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1.
Biomedicines ; 12(7)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39062124

RESUMO

Background: The positivity of anti-RNP autoantibodies as biological criteria for the diagnosis of mixed connective tissue disease (MCTD) has recently divided the rheumatology community. Autoantigenicity of the U1-snRNP complex tends to generate multiple autoantibodies against RNP-A, -C and -70 KDa or Sm proteins. The aim of this study is to identify the most informative autoantibodies in clinical practice, in particular, to contribute to differential diagnosis between MCTD and systemic lupus erythematosus (SLE). Methods: Sera from 74 patients positive for anti-RNP autoantibodies were selected over a period of one year of laboratory practice. Autoantibodies directed against extractable nuclear antigen, RNP proteins (A, C, 70 KDa) and 40 kDa fragments of RNP-70 KDa were investigated by using quantitative fluoroenzymatic assay and Western blot analysis. Results: Among the 74 patients, 40 patients were diagnosed with SLE, 20 with MCTD, six with another autoimmune disease, three with SARS-CoV-2 infection, three with cancer and two were healthy. No preferential clinical association of IgG or IgM autoantibodies directed against each of the RNP proteins was found between SLE and MCTD. In contrast, the proportion of autoantibodies directed against the RNP component within the U1-snRNP complex showed a significantly higher RNP index in patients with MCTD than in those with SLE (p = 0.011), with good performance (sensitivity: 69.2%, specificity: 88.9%). Conclusions: The analysis of the proportion of the different autoantibodies directed against the U1-snRNP complex is more informative than the analysis of each autoantibody separately. A follow-up of patients could be informative about the interest of the RNP index as a predictor of disease evolution.

2.
J Invest Dermatol ; 142(12): 3200-3210.e5, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35690141

RESUMO

CD146 involvement was recently described in skin fibrosis of systemic sclerosis through its regulation of the Wnt pathway. Because the interaction between Wnt and ROS signaling plays a major role in fibrosis, we hypothesized that in systemic sclerosis, CD146 may regulate Wnt/ROS crosstalk. Using a transcriptomic and western blot analysis performed on CD146 wild-type or knockout mouse embryonic fibroblasts, we showed a procanonical Wnt hallmark in the absence of CD146 that is reversed when CD146 expression is restored. We found an elevated ROS content in knockout cells and an increase in DNA oxidative damage in the skin sections of knockout mice compared with those of wild-type mice. We also showed that ROS increased CD146 and its noncanonical Wnt ligand, WNT5A, only in wild-type cells. In humans, fibroblasts from patients with systemic sclerosis presented higher ROS content and expressed CD146, whereas control fibroblasts did not. Moreover, CD146 and its ligand were upregulated by ROS in both human fibroblasts. The increase in bleomycin-induced WNT5A expression was abrogated when CD146 was silenced. We showed an interplay between Wnt and ROS signaling in systemic sclerosis, regulated by CD146, which promotes the noncanonical Wnt pathway and prevents ROS signaling, opening the way for innovative therapeutic strategies.


Assuntos
Escleroderma Sistêmico , Via de Sinalização Wnt , Humanos , Animais , Camundongos , Via de Sinalização Wnt/fisiologia , Antígeno CD146/genética , Antígeno CD146/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ligantes , Fibroblastos/metabolismo , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/metabolismo , Fibrose , Estresse Oxidativo
3.
Biomedicines ; 8(12)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352759

RESUMO

The fundamental role of cell adhesion molecules in mediating various biological processes as angiogenesis has been well-documented. CD146, an adhesion molecule of the immunoglobulin superfamily, and its soluble form, constitute major players in both physiological and pathological angiogenesis. A growing body of evidence shows soluble CD146 to be significantly elevated in the serum or interstitial fluid of patients with pathologies related to deregulated angiogenesis, as autoimmune diseases, obstetric and ocular pathologies, and cancers. To block the undesirable effects of this molecule, therapeutic antibodies have been developed. Herein, we review the multifaceted functions of CD146 in physiological and pathological angiogenesis and summarize the interest of using monoclonal antibodies for therapeutic purposes.

4.
Expert Rev Respir Med ; 14(8): 845-850, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32394768

RESUMO

BACKGROUND: Inflammatory myopathies (IM) are characterized by muscular inflammation that can be associated with systemic disorders including lung. Anti-NXP2 antibody (Ab) is a rare myositis-specific antibody and its association with pulmonary involvement is still unknown. In this study, we investigated the characteristics of lung disease in patients with IM associated with anti-NXP2 Ab. METHODS: Adult patients with confirmed IM and positive anti-NXP2 antibodies were recruited in our University departments (Assistance Publique- Hôpitaux de Marseille, France), between 2015 and 2019 to perform a retrospective study. RESULTS: Seven patients were identified. Mean age was 55 ± 13 years, with a predominance of females (71%). Two patients (29%) had respiratory symptoms. CT-scan shows abnormalities in three patients (organizing pneumonia, nonspecific interstitial pneumonia, and bilateral pleural effusion). An altered diffusing capacity for carbon monoxide was found in four patients. CONCLUSION: We observed that subclinical lung involvement is not rare in patients with IM associated with positive anti-NXP2 Ab, with various radiological patterns and a significant lung function defect. Such data deserve to be known by the pulmonologist in order to perform a complete lung screening in all patients with positive anti-NXP2 antibody and to detect earlier a concomitant lung impairment.


Assuntos
Adenosina Trifosfatases/imunologia , Autoanticorpos/sangue , Proteínas de Ligação a DNA/imunologia , Pneumopatias/sangue , Miosite/sangue , Adulto , Idoso , Feminino , França , Humanos , Pneumopatias/complicações , Pneumopatias/diagnóstico por imagem , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/complicações , Miosite/imunologia , Estudos Retrospectivos
5.
Sci Rep ; 9(1): 17721, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776424

RESUMO

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of RORγT, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.


Assuntos
Antígeno CD146/genética , Escleroderma Sistêmico/sangue , Células Th17/imunologia , Adulto , Idoso , Biomarcadores/sangue , Antígeno CD146/sangue , Antígeno CD146/metabolismo , Feminino , Humanos , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/sangue
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