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1.
Int J Mol Sci ; 25(2)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38255879

RESUMO

Lupus nephritis (LN), a major complication in individuals diagnosed with systemic lupus erythematosus, substantially increases morbidity and mortality. Despite marked improvements in the survival of patients with severe LN over the past 50 years, complete clinical remission after immunosuppressive therapy is achieved in only half of the patients. Therefore, timely detection of LN is vital for initiating prompt therapeutic interventions and improving patient outcomes. Biomarkers have emerged as valuable tools for LN detection and monitoring; however, the complex role of these biomarkers in LN pathogenesis remains unclear. Renal biopsy remains the gold standard for the identification of the histological phenotypes of LN and guides disease management. However, the molecular pathophysiology of specific renal lesions remains poorly understood. In this review, we provide a critical, up-to-date overview of the latest developments in the field of LN biomarkers.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/diagnóstico , Biomarcadores , Rim , Fenótipo , Resposta Patológica Completa
2.
Int J Mol Sci ; 25(19)2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39408836

RESUMO

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the production of autoreactive B and T cells and cytokines, leading to chronic inflammation affecting multiple organs. SLE is associated with significant complications that substantially increase morbidity and mortality. Given its complex pathogenesis, conventional treatments for SLE often have significant side effects and limited efficacy, necessitating the exploration of novel therapeutic strategies. One promising approach is the use of chimeric antigen receptor (CAR)-T-cell therapy, which has shown remarkable success in treating refractory hematological malignancies. This review provides a comprehensive analysis of the current use of CAR-T-cell therapy in SLE.


Assuntos
Imunoterapia Adotiva , Lúpus Eritematoso Sistêmico , Receptores de Antígenos Quiméricos , Linfócitos T , Humanos , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais
3.
Clin Immunol ; 247: 109239, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682593

RESUMO

T-helper cytokines interferon gamma (IFNÉ£), interleukin 17 (IL-17) and IL-10 impact systemic lupus erythematosus (SLE) directly and indirectly via modulation of autoAb production. We determined the separate and combined effects on clinical manifestations of SLE (N = 62). IFNÉ£, IL-17 but not IL-10 were significantly elevated in patients with SLE. IFNÉ£ positively correlated with anti-DNA and anti-SSA. IL-17 positively correlated with anti-SSA and was significantly higher in patients with discoid rash and class V LN. IL-10 did not correlate with circulating autoantibodies but was significantly elevated in patients with LN. Patients with LN had elevated plasma levels of anti-DNA and anti-Sm/ribonuclear protein (RNP). Anti-Sm/RNP levels were decreased in patients with acute mucocutaneous manifestations, including photosensitivity and/or malar rash. The study provides critical insights into pathological mechanisms of LN, which could help guide future diagnoses and therapies.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Citocinas , Interleucina-17 , Estudos Transversais , Autoanticorpos , Linfócitos T , Interferon gama , Anticorpos Antinucleares
4.
Clin Immunol ; 257: 109842, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37981105

RESUMO

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet+CD11c+ IgD+ activated naive B cells (aNAV) was higher in females and was associated with increased T-bet+CD11c+ IgD- age-related B cells, Fas+GL7+ germinal center B cells, Cxcr5-Icos+ peripheral T-helper cells, and Cxcr5+Icos+ follicular T-helper cells. IFN-ß was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.


Assuntos
Linfócitos B , Lúpus Eritematoso Sistêmico , Animais , Feminino , Humanos , Masculino , Camundongos , Autoanticorpos , Cruzamentos Genéticos , Centro Germinativo , Lúpus Eritematoso Sistêmico/genética , Camundongos Endogâmicos C57BL , Linfócitos T Auxiliares-Indutores , Caracteres Sexuais
5.
Curr Rheumatol Rep ; 25(12): 295-306, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38102522

RESUMO

PURPOSE OF REVIEW: To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA). RECENT FINDINGS: Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors. Suboptimal treatment of treatment-refractory RA patients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk. New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Cardiovasculares , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/efeitos adversos , Medição de Risco
6.
J Rheumatol ; 50(6): 817-826, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36521917

RESUMO

OBJECTIVE: This single-center clinical study identifies clusters of different phenotypes and pathophysiology subtypes of patients with gout and associated comorbidities. METHODS: Patients clinically diagnosed with gout were enrolled between January 2018 and December 2019. Hierarchical cluster analyses were performed using clinical data or biological markers, inflammatory markers, and oxidative stress pathway metabolites assayed from serum and plasma samples. Subgroup clusters were compared using ANOVA for continuous data and chi-square tests for categorical data. RESULTS: Hierarchical cluster analysis identified 3 clusters. Cluster 1 (C1; n = 24) comprised dyslipidemia, hypertension, and early-onset gout, without tophi. Cluster 2 (C2; n = 25) comprised hypertension, dyslipidemia, nephrolithiasis, and obesity. Cluster 3 (C3; n = 39) comprised multiple comorbidities and tophi. Post hoc comparisons of data obtained from samples of patients in C1, C2, and C3 revealed significant differences in the levels of oxidative stress and inflammation-related markers, including 3-nitrotyrosine, tumor necrosis factor, C-reactive protein, interleukin (IL) 1ß, IL-6, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Reclustering patients based on all markers as well as on the biological markers that significantly differed among the initial clusters identified similar clusters. CONCLUSION: Oxidative stress and inflammatory marker levels may affect the development and clinical manifestations (ie, clinical phenotypes) of gout. Measuring oxidative stress and levels of inflammatory cytokines is a potential adjunctive tool and biomarker for early identification and management of gout.


Assuntos
Dislipidemias , Gota , Hipertensão , Hiperuricemia , Humanos , Estudos Transversais , Gota/diagnóstico , Gota/epidemiologia , Hipertensão/complicações , Análise por Conglomerados , Biomarcadores , Hiperuricemia/complicações
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