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1.
Medicine (Baltimore) ; 99(47): e23184, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217825

RESUMO

Lipid abnormalities are an important cause of premature atherosclerosis in patients with systemic lupus erythematosus (SLE). This longitudinal study investigates the changes in lipid profile and arterial stiffness with SLE disease activity index (SLEDAI) reduction.Fifty one female SLE patients with baseline SLEDAI ≥ 6 and SLEDAI reduction >3 at 1-year follow-up were included. Neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and mean brachial-ankle pulse wave velocity (baPWV) were measured and compared between baseline and 1-year follow-up. Correlations between inflammation biomarkers, SLEDAI, mean baPWV and lipid profile were assessed.We observed significant decreases in ESR, mean baPWV, TG and TC to HDL-C ratio compared with baseline at 1-year follow up, while HDL-C, hsCRP, and NLR were not significantly changed. Significant correlations were found between the reductions in ESR and TG, and SLEDAI and mean baPWV, with adjustment to age, disease duration, blood pressure, and medications (prednisone, immunosuppressants and ARB/ACEI).SLE patients experiencing SLEDAI reductions showed improvements in arterial stiffness. This finding may provide insight into the beneficial effects of reducing SLEDAI on atherosclerosis risk in SLE.


Assuntos
Lipídeos/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Rigidez Vascular , Adulto , Índice Tornozelo-Braço , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/sangue , Medição de Risco , Fatores de Risco
2.
Egypt J Immunol ; 27(1): 45-53, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33180387

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the complement system plays a role in its pathogenesis. Mannose-binding lectin (MBL) is a serum protein, being a component of innate immune system, it is responsible for lectin pathway of complement activation. The presence of several polymorphisms at the coding regions of the MBL-2 gene, especially single point mutation at codon 54, leads to decreased level and /or functional deficits of MBL, which seems to be a risk factor for occurrence of autoimmune diseases, such as in SLE. So, this study was carried out to determine the role of the serum MBL concentration and the genetic polymorphisms of MBL-2 gene exon 1 codon 54 in Egyptian patients with SLE. Forty-eight SLE patients and 48 matched healthy controls were investigated. MBL serum level was measured by ELISA technique. MBL-2 polymorphism at exon 1 codon 54 was determined by PCR-RFLP. Our results revealed a significant reduction in MBL serum level among SLE patient group in comparison to the control group (P < 0.001). MBL-2 genotyping among SLE patients, revealed the wild type (A/A) in 52.1% and mutant types (A/B, B/B) in 47.9%. While among healthy controls, the wild type was detected in 81.2% and the mutant types in 18.8% with a statistically significant association between this polymorphism and SLE susceptibility (P=0.008). Comparison of MBL serum level among different genotypes within the patient group showed that the mutant allele had a suppressive effect on MBL serum level. In conclusion, carrying MBL-2 exon-1 codon 54 variant allele B was shown to be a risk factor for SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Lectina de Ligação a Manose , Alelos , Egito , Predisposição Genética para Doença , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/genética , Polimorfismo de Fragmento de Restrição
3.
Medicine (Baltimore) ; 99(41): e22607, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031316

RESUMO

Ikaros family zinc finger 1(IKZF1) encodes a lymphoid-restricted zinc finger transcription factor named Ikaros that regulates lymphocyte differentiation and proliferation as well as self-tolerance. Increasing evidence indicates that IKZF1 could contribute to the pathogenesis of autoimmune diseases. Recent research has provided evidence that IKZF1 might correlate with Systemic lupus erythematosus (SLE), but no clear definition has been made yet. In this study, we focus on the relationship between IKZF1 polymorphisms and SLE susceptibility, cytokine levels, and clinical characteristics in the Chinese Han population.One thousand seventy-six subjects, including 400 SLE patients and 676 healthy controls, were included in this study. Three single nucleotide polymorphisms within IKZF1 containing rs4917014, rs11980379, and rs4132601 were genotyped in all subjects by an improved multiplex ligation detection reaction technique. 143 subjects from SLE patients were randomly selected for testing the levels of serum cytokines. The clinical characteristics of SLE patients were gathered and collated from medical records. The data were analyzed mainly using SPSS20.0 (SPSS lnc., Chicago, IL).Significant relationships were observed between rs4132601 and SLE susceptibility, CD40 ligand, and malar rash (P < .001, P = .04, and P = .01, respectively). In addition, significant relationships were observed between rs4917014 and susceptibility, granzyme B level, and hematological disorder in SLE (P = .005, P = .03 and P = .005, respectively).The results further support that IKZF1 may have an important role in the development and pathogenesis of SLE. Allele G of rs4132601 and rs4917014 is related to a decreased risk of SLE occurrence and associated with clinical features in SLE patients, including CD40 ligand level, granzyme B level, malar rash, and hematological disorder, which play important roles in disease progression.


Assuntos
Citocinas/sangue , Fator de Transcrição Ikaros/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
4.
Medicine (Baltimore) ; 99(35): e21888, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871918

RESUMO

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with considerable genetic predisposition. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) is crucial for the innate immunity and implicated in SLE pathogenesis. Accordingly, we conducted a case-control study to find the association of NLRP3 variations with SLE susceptibility and disease activity.Three single nucleotide polymorphisms of NLRP3 (rs3806268, rs4612666, and rs10754558) were genotyped in 400 SLE patients and 400 healthy controls; the patients were further divided into mild-to-moderate or high disease activity subgroup. Serum cytokines, complements, and autoantibodies were also detected.We found that rs4612666 TT genotype conferred a higher risk of severe disease activity with adjusted odds ratio = 2.08, P = .02 and adjusted odds ratio  = 2.34, P = .01 in the codominant and recessive model, respectively. Nevertheless, there was no association between the 3 single nucleotide polymorphisms of NLRP3 gene and SLE susceptibility. In addition, C4 decreased significantly in rs3806268 GG (P < .001) and rs4612666 TT genotype carriers (P = .03). A higher trend of interleukin-1ß and interleukin-γ release were identified in rs3806268 AA and rs10754558 CC genotype carriers, respectively.NLRP3 polymorphisms are associated with SLE disease activity and hypocomplementemia. Interleukin-1ß and interleukin-γ levels in SLE patients are correlated with NLRP3 variants as well.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Complemento C4/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Subunidade gama Comum de Receptores de Interleucina/sangue , Interleucina-1beta/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
5.
Sci Rep ; 10(1): 15031, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929141

RESUMO

Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case-control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
6.
Sci Rep ; 10(1): 14178, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843681

RESUMO

Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease. Detection of anti-nuclear antibodies (ANA) is fundamental for the diagnosis of SLE. In the present study, we found that the level of core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) is markedly up-regulated on immunoglobulin G (IgG) in the sera of SLE patients detected by Aspergillus oryzae lectin (AOL) blot. In sandwich Dot enzyme-linked immunosorbent assay (Dot-ELISA), the core fucosylation level was also found significantly increased in the sera from SLE patients with a higher ANA titer. To establish a rapid and sensitive laboratory test for the diagnosis of SLE, we prokaryotically expressed AOL and C3-D1-C3-D2-C3 of protein G (SpG3), and generate AOL-conjugated colloid gold immunochromatographic strips (ICS). The detection limit of core fucosylated IgG was 10 µg/mL for AOL-conjugated colloid gold ICS. As well as indirect immunofluorescence, the AOL-conjugated colloid gold ICS showed reliable results in the serum of 39 SLE patients. Our results indicated that the AOL-conjugated colloid gold ICS could serve as a rapid test for the detection of ANA and suspected cases of SLE.


Assuntos
Cromatografia de Afinidade , Imunoglobulina G/química , Lúpus Eritematoso Sistêmico/diagnóstico , Fitas Reagentes , Adolescente , Adulto , Idoso , Animais , Anticorpos Antinucleares/sangue , Aspergillus oryzae , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Fucose/metabolismo , Fucosiltransferases/deficiência , Fucosiltransferases/metabolismo , Glicosilação , Coloide de Ouro , Humanos , Immunoblotting , Imunoglobulina G/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Lectinas de Plantas , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes de Fusão , Organismos Livres de Patógenos Específicos , Adulto Jovem
7.
Reumatol. clín. (Barc.) ; 16(4): 255-261, jul.-ago. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-194951

RESUMO

OBJECTIVES: To investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients. PATIENTS AND METHODS: This study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection. RESULTS: The NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9. CONCLUSION: NLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging


OBJETIVOS: Investigar el papel de la proporción de neutrófilos a linfocitos (NLR), y la relación de plaquetas a linfocitos (PLR) como marcadores de actividad en el lupus eritematoso sistémico (LES) sin nefritis, y pacientes con nefritis lúpica (NL). PACIENTES Y MÉTODOS: Este estudio incluyó a 60 pacientes con LES con NL, 60 pacientes con LES sin afectación renal y 30 controles sanos. Analizamos las correlaciones entre NLR y PLR con la actividad de la enfermedad y la afección renal. RESULTADOS: La NLR de los pacientes con LES fue mucho más alta que los de los controles. Ambas razones mostraron valores significativamente mayores en pacientes con LES con enfermedad activa. La NLR y la PLR se correlacionaron positivamente con SLEDAI, ESR y CRP y se correlacionaron negativamente con C4. Los pacientes con LES con LN tenían niveles más altos de NLR que aquellos sin nefritis. La NLR mostró correlaciones positivas con BUN, urea sérica, creatinina sérica y proteína urinaria de 24h. Encontramos que la NLR está relacionada con el nivel de anti-dsDNA y las clases de biopsia renal. Mientras que la PLR estaba relacionada solo con anti-dsDNA. La mejor NLR para predecir la enfermedad activa del SLE fue de 2,2 y el mejor valor de corte de la PLR fue 132,9. CONCLUSIÓN: La NLR y la PLR son marcadores inflamatorios útiles para evaluar la actividad de la enfermedad en pacientes con LES. Además, la NLR podría reflejar la afectación renal en pacientes con LES y se asocia con las diferentes clases de su estadificación histológica


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Lúpus Eritematoso Sistêmico/sangue , Plaquetas/imunologia , Neutrófilos , Linfócitos , Lúpus Eritematoso Sistêmico/fisiopatologia , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Estudos Transversais , Biomarcadores , Curva ROC
8.
Clin Rheumatol ; 39(9): 2811-2815, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32720260

RESUMO

In the midst of the COVID-19 pandemic, further understanding of its complications points towards dysregulated immune response as a major component. Systemic lupus erythematosus (SLE) is also a disease of immune dysregulation leading to multisystem compromise. We present a case of new-onset SLE concomitantly with COVID-19 and development of antiphospholipid antibodies. An 18-year-old female that presented with hemodynamic collapse and respiratory failure, progressed to cardiac arrest, and had a pericardial tamponade drained. She then progressed to severe acute respiratory distress syndrome, severe ventricular dysfunction, and worsening renal function with proteinuria and hematuria. Further studies showed bilateral pleural effusions, positive antinuclear and antidouble-stranded DNA antibodies, lupus anticoagulant, and anticardiolipin B. C3 and C4 levels were low. SARS-Cov-2 PCR was positive after 2 negative tests. She also developed multiple deep venous thrombosis, in the setting of positive antiphospholipid antibodies and lupus anticoagulant. In terms of pathophysiology, COVID-19 is believed to cause a dysregulated cytokine response which could potentially be exacerbated by the shift in Th1 to Th2 response seen in SLE. Also, it is well documented that viral infections are an environmental factor that contributes to the development of autoimmunity; however, COVID-19 is a new entity, and it is not known if it could trigger autoimmune conditions. Additionally, it is possible that SARS-CoV-2, as it happens with other viruses, might lead to the formation of antiphospholipid antibodies, potentially contributing to the increased rates of thrombosis seen in COVID-19.


Assuntos
Síndrome Antifosfolipídica/imunologia , Infecções por Coronavirus/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Pneumonia Viral/imunologia , Adolescente , Anemia/etiologia , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Anuria/etiologia , Betacoronavirus , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Complemento C3/imunologia , Complemento C4/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , DNA/imunologia , Ecocardiografia , Evolução Fatal , Feminino , Parada Cardíaca/etiologia , Hematúria/etiologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Pandemias , Posicionamento do Paciente , Pericardiocentese , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Decúbito Ventral , Proteinúria/etiologia , Diálise Renal , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Respiração Artificial , /terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Trombocitopenia/etiologia , Trombose Venosa/etiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem
9.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702995

RESUMO

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Assuntos
Afro-Americanos , Betacoronavirus , Infecções por Coronavirus/etnologia , Pandemias , Pneumonia Viral/etnologia , Trombofilia/etnologia , Tromboembolia Venosa/etnologia , Afro-Americanos/genética , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Anticoagulantes/uso terapêutico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Estudos de Associação Genética , Predisposição Genética para Doença , Disparidades em Assistência à Saúde , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Polimorfismo de Nucleotídeo Único , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
10.
Clin Exp Rheumatol ; 38(6): 1238-1246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32662402

RESUMO

OBJECTIVES: Initial studies investigating peripheral levels of leptin and soluble leptin receptor (LepR) in systemic lupus erythematosus (SLE) patients have generated a number of controversial results. Thus, we conducted a meta-analysis to evaluate the circulating leptin level, soluble LepR level and related gene polymorphism in SLE patients. METHODS: We performed a meta-analysis comparing the circulating leptin level, LepR level and their gene polymorphism in patients with SLE to controls, and evaluate the relationship between leptin levels, LepR levels and SLE disease activity. Pubmed, Embase, Cochrane, CNKI, WanFang and VIP databases were searched systematically with no restriction to languages and years (up to Feb. 2020). Stata v. 14.0 was used to calculate statistical data. RESULTS: 34 articles involving 7337 SLE patients and 6866 healthy controls were included in this meta-analysis. Compared with the controls, SLE patients had a significantly higher level of leptin, in particular for active SLE patients, regardless of sample size, source, or assay method. The elevated leptin level was only found in the female SLE group, but not in the male SLE group. Apart from the South American subgroup, other ethnicity subgroups showed significantly higher levels of leptin in SLE patients. A marginally lower level of LepR in SLE patients was also observed. The LepR gene rs1137101 variant (i.e. AG+GG) was borderline significantly associated with the increased risk of SLE. CONCLUSIONS: Our meta-analysis revealed thta SLE patients had an elevated leptin level and decreased LepR level. LepR gene rs1137101 mutation might be associated with increased susceptibility to SLE.


Assuntos
Leptina , Lúpus Eritematoso Sistêmico , Receptores para Leptina , Feminino , Predisposição Genética para Doença , Humanos , Leptina/sangue , Leptina/genética , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Masculino , Pacientes , Polimorfismo Genético , Receptores para Leptina/sangue , Receptores para Leptina/genética
11.
Arthritis Res Ther ; 22(1): 125, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: covidwho-457521

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. METHODS: A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. RESULTS: The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. CONCLUSIONS: A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Monitoramento de Medicamentos/normas , Hidroxicloroquina/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pandemias , Pneumonia Viral , Adulto , Idoso , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Espectrometria de Massas/métodos , Espectrometria de Massas/normas , Pessoa de Meia-Idade , Plasma , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Soro , Adulto Jovem
12.
Arthritis Rheumatol ; 72(10): 1587-1595, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32524751

RESUMO

Patients with systemic lupus erythematosus (SLE) display increased numbers of immature neutrophils in the blood, but the exact role of these immature neutrophils is unclear. Neutrophils that sediment within the peripheral blood mononuclear cell fraction after density centrifugation of blood are generally defined as low-density neutrophils (LDNs). Far beyond antimicrobial functions, LDNs are emerging as decision-shapers during innate and adaptive immune responses. Traditionally, neutrophils have been viewed as a homogeneous population. However, the various LDN populations identified in SLE to date are heterogeneously composed of mixed populations of activated mature neutrophils and immature neutrophils at various stages of differentiation. Controversy also surrounds the role of LDNs in SLE in terms of whether they are proinflammatory or polymorphonuclear myeloid-derived suppressor cells. It is clear that LDNs in SLE can secrete increased levels of type I interferon (IFN) and that they contribute to the cycle of inflammation and tissue damage. They readily form neutrophil extracellular traps, exposing modified autoantigens and oxidized mitochondrial DNA, which contribute to autoantibody production and type I IFN signaling, respectively. Importantly, the ability of LDNs in SLE to perform canonical neutrophil functions is polarized, based on mature CD10+ and immature CD10- neutrophils. Although this field is still relatively new, multiomic approaches have advanced our understanding of the diverse origins, phenotype, and function of LDNs in SLE. This review updates the literature on the origin and nature of LDNs, their distinctive features, and their biologic roles in the immunopathogenesis and end-organ damage in SLE.


Assuntos
Armadilhas Extracelulares/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Neutrófilos/metabolismo , Humanos , Contagem de Leucócitos
13.
Nature ; 582(7813): 577-581, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499649

RESUMO

Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren's syndrome affect nine times more women than men1, whereas schizophrenia affects men with greater frequency and severity relative to women2. All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren's syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus3-6. Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia7, generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren's syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren's syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren's syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma8,9 in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women's greater risk of SLE and Sjögren's syndrome and men's greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses.


Assuntos
Complemento C3/genética , Complemento C4/genética , Lúpus Eritematoso Sistêmico/genética , Caracteres Sexuais , Síndrome de Sjogren/genética , Adulto , Alelos , Complemento C3/análise , Complemento C3/líquido cefalorraquidiano , Complemento C4/análise , Complemento C4/líquido cefalorraquidiano , Feminino , Predisposição Genética para Doença , Antígenos HLA/genética , Haplótipos , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/líquido cefalorraquidiano , Complexo Principal de Histocompatibilidade/genética , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/sangue , Síndrome de Sjogren/líquido cefalorraquidiano , Adulto Jovem
14.
Nat Commun ; 11(1): 2859, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503973

RESUMO

Mature double negative (DN) T cells are a population of αß T cells that lack CD4 and CD8 coreceptors and contribute to systemic lupus erythematosus (SLE). The splenic marginal zone macrophages (MZMs) are important for establishing immune tolerance, and loss of their number or function contributes to the progression of SLE. Here we show that loss of MZMs impairs the tolerogenic clearance of apoptotic cells and alters the serum cytokine profile, which in turn provokes the generation of DN T cells from self-reactive CD8+ T cells. Increased Ki67 expression, narrowed TCR V-beta repertoire usage and diluted T-cell receptor excision circles confirm that DN T cells from lupus-prone mice and patients with SLE undergo clonal proliferation and expansion in a self-antigen dependent manner, which supports the shared mechanisms for their generation. Collectively, our results provide a link between the loss of MZMs and the expansion of DN T cells, and indicate possible strategies to prevent the development of SLE.


Assuntos
Autoantígenos/imunologia , Interleucina-17/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Subpopulações de Linfócitos T/imunologia , Transferência Adotiva , Animais , Autoantígenos/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Tolerância Imunológica , Antígeno Ki-67/imunologia , Antígeno Ki-67/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Macrófagos/imunologia , Camundongos , Camundongos Knockout , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/metabolismo
16.
Arthritis Res Ther ; 22(1): 125, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32475347

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. METHODS: A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. RESULTS: The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. CONCLUSIONS: A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Monitoramento de Medicamentos/normas , Hidroxicloroquina/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pandemias , Pneumonia Viral , Adulto , Idoso , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Espectrometria de Massas/métodos , Espectrometria de Massas/normas , Pessoa de Meia-Idade , Plasma , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Soro , Adulto Jovem
17.
Nutr Metab Cardiovasc Dis ; 30(7): 1147-1151, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451275

RESUMO

BACKGROUND AND AIM: Systemic lupus erythematosus (SLE) is associated with accelerated atherogenesis. Traditional risk factors do not seem to fully explain this process in patients with SLE and no other imaging/serum biomarkers have so far improved risk stratification. Here, we focused on the role of adiponectin in women with SLE. METHODS AND RESULTS: This is a sub-analysis of a validated cohort enrolling eighty females (age 18-65 years) affected by SLE. Patient underwent a single blood sampling and carotid echography. Serum adipocytokines (i.e. leptin, resistin and adiponectin) were assessed by enzyme-linked immunosorbent assay (ELISA). Patients with a carotid plaque (n = 23) were older, with longer duration of the disease, chronic use of corticosteroids, and immunosuppressive therapies. As expected, patients with a carotid plaque had increased vascular risk and high serum levels of inflammatory biomarkers, total and LDL cholesterol and adiponectin. Significant positive correlation between serum adiponectin and presence of a carotid plaque was found independently of patient age, SCORE Risk Charts, duration of disease, and SLE treatments. CONCLUSIONS: These results indicate that high serum adiponectin is associated with accelerated carotid atherosclerosis in SLE young women and it might be useful to improve vascular risk stratification in this patient setting.


Assuntos
Adiponectina/sangue , Doenças das Artérias Carótidas/sangue , Lúpus Eritematoso Sistêmico/sangue , Placa Aterosclerótica , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Regulação para Cima , Adulto Jovem
18.
Ann Biol Clin (Paris) ; 78(2): 201-205, 2020 04 01.
Artigo em Francês | MEDLINE | ID: mdl-32319950

RESUMO

Anti-citrullinated cyclic peptide antibodies (ACPA) were initially considered very specific for the diagnosis of rheumatoid arthritis (RA), and can predict the prognosis of the disease. However, these antibodies can be detected in other autoimmune diseases, including systemic lupus erythematosus (SLE), the most common manifestation of which is inflammatory arthritis, which is often found in early-stage rheumatoid arthritis. The aim of our study is to evaluate the prevalence of ACPA antibodies and to analyze the profiles of their associations with autoantibodies specific to lupus, in order to look for a possible rhupus overlap syndrome in our patients. This is a retrospective study, carried out at the immunology unit, at Blida University Hospital, Algeria, involving 96 lupus patients, diagnosed according to the criteria of the American college of rheumatology (ACR). ACPA have been identified by the ELISA technique. ACPA was positive in 14,56% of our patients, whereas anti-DNA, anti-Sm and rheumatoid factor (RF) autoantibodies were positive, respectively in 47.09%, 35.41%, and in 26.04% of our patients. In addition, the presence of ACPA with anti DNA was found in 12.5% of patients. Of the 14 with ACPA+, 57.14% had arthritis. Our results confirm that ACPA auto-antibodies do not represent a pathognomonic criterion of RA. This sometimes makes the differential diagnosis with lupus difficult especially at the beginning of the disease.


Assuntos
Artrite Reumatoide/sangue , Biomarcadores/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Fator Reumatoide/sangue , Adolescente , Adulto , Idoso , Argélia/epidemiologia , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/sangue , Artrite Reumatoide/epidemiologia , Autoanticorpos/análise , Autoanticorpos/sangue , Biomarcadores/análise , Criança , Citrulinação , Comorbidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Peptídeos Cíclicos/metabolismo , Estudos Retrospectivos , Fator Reumatoide/análise , Adulto Jovem
19.
PLoS One ; 15(4): e0231622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298352

RESUMO

OBJECTIVES: Nonthyroidal illness syndrome (NTIS), also known as low triiodothyronine (T3) syndrome, frequently affects patients with systemic lupus erythematosus (SLE) and may affect lipid metabolism. Dyslipidemia is highly prevalent and associated with the long-term prognosis of SLE. The aim of the present study was to explore the clinical significance of NTIS on disease activity and dyslipidemia in patients with SLE. METHODS: Clinical and laboratory data were collected retrospectively from 223 patients with SLE. The correlation between free triiodothyronine (FT3), SLE disease activity, and lipid profiles were estimated. The correlation coefficient (r) was calculated using a Pearson's regression model. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for dyslipidemia in SLE. RESULTS: Serum FT3 levels were negatively correlated with the levels of 24 h urine protein (UP), blood urea nitrogen (BUN), creatinine (Cr) and SLE disease activity index (SLEDAI) (all p < 0.001) in NTIS patients but not in euthyroid patients. ApoB/ApoA1 was significantly correlated with SLEDAI (p < 0.01) in NTIS patients and CRP (p < 0.001) and ESR (p < 0.01) in euthyroid patients. A multivariate analysis revealed that only FT3 exhibited an independent negative association with dyslipidemia (P = 0.01; OR = 0.48; 95% CI 0.27-0.85). CONCLUSION: NTIS frequently occurs in patients with SLE. Low FT3 is associated with disease activity in SLE patients complicated with NTIS. Low FT3 is an independent risk factor for dyslipidemia in patients with SLE.


Assuntos
Dislipidemias/complicações , Síndromes do Eutireóideo Doente/complicações , Lúpus Eritematoso Sistêmico/complicações , Adulto , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Dislipidemias/sangue , Síndromes do Eutireóideo Doente/sangue , Feminino , Humanos , Lipídeos/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tri-Iodotironina/sangue , Adulto Jovem
20.
Clinics (Sao Paulo) ; 75: e1450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321113

RESUMO

Systemic lupus erythematosus (SLE) is a chronic systematic autoimmune disease. Current methods of diagnosing SLE or evaluating its activity are complex and expensive. Numerous studies have suggested that neutrophil-to-lymphocyte ratio (NLR) is closely correlated with the presence of SLE and its activity, suggesting that it may serve as a diagnostic and monitoring indicator for SLE. Therefore, we performed a meta-analysis to systematically assess the association between NLR and SLE. We performed a literature search until 12 April 2019 in the PubMed, Web of Science, and China National Knowledge Infrastructure databases. Cross-sectional studies comparing the NLR of SLE patients versus those of healthy controls, of active versus inactive SLE patients, and of SLE patients with versus without lupus nephritis were considered for inclusion. Mean intergroup NLR differences were estimated using standardized mean differences and their 95% confidence intervals. Study quality was assessed using the Agency for Healthcare Research and Quality instrument for cross-sectional studies. Fourteen studies with 1,781 SLE patients and 1,330 healthy controls were included in this meta-analysis. The pooled results showed that the NLR was significantly higher in SLE patients than in healthy controls, in active SLE patients than in inactive SLE patients, and in SLE patients with lupus nephritis than in those without lupus nephritis. NLR may be an indicator for monitoring disease activity and reflecting renal involvement in SLE patients. Nevertheless, more high-quality studies are warranted to further validate our findings.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Linfócitos/patologia , Neutrófilos/patologia , China , Estudos Transversais , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico
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