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1.
Medicine (Baltimore) ; 99(33): e21121, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871981

RESUMO

BACKGROUD: Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and efficacy of MMF in patients with LN, no definitive meta-analysis has yet been conducted in Chinese patients. This analysis investigated the efficacy and safety of MMF in Chinese patients with proliferative LN. METHODS: A systematic literature search was conducted to select randomized controlled trials that reported at least one of the following: complete remission (CR), partial remission, total remission (TR; defined as complete remission + partial remission), relapse rate, serum creatinine, creatinine clearance, end-stage renal disease, death, infections, amenorrhea, leukopenia, alopecia, gastrointestinal symptoms, or liver damage. RESULTS: Eighteen trials (927 patients) were included; 14 (750 patients) reported CR, partial remission, and TR. Two trials (58 patients) reported relapse rates during maintenance treatment. MMF induction significantly improved CR and TR vs cyclophosphamide (relative risk 1.34, 95% confidence interval: 1.13-1.58; P < .001; relative risk 1.16, 95% confidence interval: 1.02-1.33; P = .03), and was associated with significantly lower risks of infection (P < .001), amenorrhea (P < .001), leukopenia, and alopecia. No significant difference in relapse rate was evident between the MMF and azathioprine groups (P = .66). CONCLUSION: According to this meta-analysis of 18 trials, MMF is significantly more effective than cyclophosphamide induction, and is associated with reduced incidences of infections, amenorrhea, leukopenia, and alopecia in Chinese patients with proliferative LN.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etnologia , Ácido Micofenólico/uso terapêutico , Grupo com Ancestrais do Continente Asiático , China , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Inibidores Enzimáticos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Ácido Micofenólico/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Nat Commun ; 11(1): 2197, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366845

RESUMO

Emerging urinary biomarkers continue to show promise in evaluating lupus nephritis (LN). Here, we screen urine from active LN patients for 1129 proteins using an aptamer-based platform, followed by ELISA validation in two independent cohorts comprised of 127 inactive lupus, 107 active LN, 67 active non-renal lupus patients and 74 healthy controls, of three different ethnicities. Urine proteins that best distinguish active LN from inactive disease are ALCAM, PF-4, properdin, and VCAM-1 among African-Americans, sE-selectin, VCAM-1, BFL-1 and Hemopexin among Caucasians, and ALCAM, VCAM-1, TFPI and PF-4 among Asians. Most of these correlate significantly with disease activity indices in the respective ethnic groups, and surpass conventional metrics in identifying active LN, with better sensitivity, and negative/positive predictive values. Several elevated urinary molecules are also expressed within the kidneys in LN, based on single-cell RNAseq analysis. Longitudinal studies are warranted to assess the utility of these biomarkers in tracking lupus nephritis.


Assuntos
Aptâmeros de Peptídeos/metabolismo , Biomarcadores/urina , Nefrite Lúpica/diagnóstico , Proteínas/análise , Molécula de Adesão de Leucócito Ativado/urina , Adulto , Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Selectina E/análise , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Nefrite Lúpica/etnologia , Nefrite Lúpica/urina , Properdina/urina , Sensibilidade e Especificidade , Molécula 1 de Adesão de Célula Vascular/urina , Adulto Jovem
3.
Arthritis Care Res (Hoboken) ; 72(5): 622-629, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31115180

RESUMO

OBJECTIVE: The California Lupus Surveillance Project (CLSP) is a population-based registry of individuals with systemic lupus erythematosus (SLE) residing in San Francisco County, California from 2007 to 2009, with a special focus on Asian/Pacific Islander and Hispanic patients. We used retrospective CLSP data to analyze racial and ethnic differences in lupus manifestations and in the timing and risk of developing severe manifestations. METHODS: A total of 724 patients with SLE were retrospectively identified. Prevalence ratios (PRs) of SLE manifestations were calculated using Poisson regression models stratified by race/ethnicity and adjusted for sex, age at SLE diagnosis, and disease duration. We studied onset of severe SLE manifestations after SLE diagnosis using Kaplan-Meier methods to examine time-to-event and Cox proportional hazards regression models to estimate hazard ratios (HRs). White patients were the referent group in all analyses. RESULTS: African Americans, Asian/Pacific Islanders, and Hispanic patients had increased prevalence of renal manifestations (PR 1.74 [95% confidence interval (95% CI) 1.40-2.16], PR 1.68 [95% CI 1.38-2.05], and PR 1.35 [95% CI 1.05-1.74], respectively). Furthermore, African Americans had increased prevalence of neurologic manifestations (PR 1.49 [95% CI 1.12-1.98]), and both African Americans (PR 1.09 [95% CI 1.04-1.15]) and Asian/Pacific Islanders (PR 1.07 [95% CI 1.01-1.13]) had increased prevalence of hematologic manifestations. African Americans, Asian/Pacific Islanders, and Hispanic patients, respectively, had higher risk of developing lupus nephritis (HR 2.4 [95% CI 1.6-3.8], HR 4.3 [95% CI 2.9-6.4], and HR 2.3 [95% CI 1.4-3.8]) and thrombocytopenia (HR 2.3 [95% CI 1.1-4.4], HR 2.3 [95% CI 1.3-4.2], and HR 2.2 [95% CI 1.1-4.7]). Asian/Pacific Islander and Hispanic patients had higher risk of developing antiphospholipid syndrome (HR 2.5 [95% CI 1.4-4.4] and HR 2.6 [95% CI 1.3-5.1], respectively). CONCLUSION: This is the first epidemiologic study comparing lupus manifestations among 4 major racial and ethnic groups. We found substantial differences in the prevalence of several clinical SLE manifestations among racial/ethnic groups and discovered that African Americans, Asian/Pacific Islanders, and Hispanic patients are at increased risk of developing several severe manifestations following a diagnosis of SLE.


Assuntos
Grupos de Populações Continentais , Grupos Étnicos , Disparidades nos Níveis de Saúde , Lúpus Eritematoso Sistêmico/etnologia , Adolescente , Adulto , California/epidemiologia , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etnologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Prognóstico , Fatores Raciais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
4.
Rheumatology (Oxford) ; 59(1): 90-98, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31236574

RESUMO

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.


Assuntos
Idade de Início , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Adolescente , Adulto , Criança , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto Jovem
5.
Clin Rheumatol ; 39(2): 365-373, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705325

RESUMO

INTRODUCTION: Smoking has been associated with increased incidence, severity of cutaneous lupus, and lupus activity. We looked at the association of both smoking and ethnicity with the individual damage items from the SLICC/ACR Damage Index. METHODS: Poisson regression was used to model the total SLICC/ACR Damage Index score against ever smoking. Cox regression was used to assess the relationship between time to individual damage items and ever smoking. Furthermore, we compared SLICC/ACR Damage Index items among African-American and Caucasian ever smokers. RESULTS: The study included 2629 patients, 52.6% Caucasian and 39.3% African-American. The prevalence of ever smokers was 35.8%. There was no significant difference in total SLICC/ACR Damage Index score between ever smokers and never smokers after adjustment for ethnicity, gender, age at diagnosis, and years of education. Ever smokers had more atherosclerotic cardiovascular damage and skin damage compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have muscle atrophy and atherosclerosis compared to Caucasian non-smokers. African-American patients who ever smoked were more likely to have skin damage compared to African-American non-smokers. African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked. CONCLUSION: Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Surprisingly, cardiovascular damage items had higher hazard ratios in Caucasian smokers than non-smokers while skin damage items hazard ratios were higher in African-American smokers compared to non-smokers.Key Points• This study is the largest cohort study to date evaluating the effect of smoking on the cumulative SLICC/ACR Damage Index and its individual damage items.• It is the only study that examined the effect of smoking on individual items of the SLICC/ACR Damage Index in terms of Caucasians vs. African-American ethnicity.• Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Compared to non-smokers, Caucasian smokers had higher risk of cardiovascular damage while African-American smokers had more skin damage.• African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked.


Assuntos
Afro-Americanos/estatística & dados numéricos , Artrite/etnologia , Doenças Cardiovasculares/etnologia , Fumar Cigarros/epidemiologia , Diabetes Mellitus/etnologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Falência Renal Crônica/etnologia , Lúpus Eritematoso Sistêmico/etnologia , Adulto , Alopecia/epidemiologia , Alopecia/etnologia , Artrite/epidemiologia , Aterosclerose/epidemiologia , Aterosclerose/etnologia , Cardiomiopatias/epidemiologia , Cardiomiopatias/etnologia , Doenças Cardiovasculares/epidemiologia , Catarata/epidemiologia , Catarata/etnologia , Cicatriz/epidemiologia , Cicatriz/etnologia , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Ex-Fumantes , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etnologia , Falência Renal Crônica/epidemiologia , Estudos Longitudinais , Lúpus Eritematoso Cutâneo/epidemiologia , Lúpus Eritematoso Cutâneo/etnologia , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/etnologia , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/epidemiologia , Atrofia Muscular/etnologia , não Fumantes , Osteonecrose/epidemiologia , Osteonecrose/etnologia , Modelos de Riscos Proporcionais , Fumantes , Tempo , Estados Unidos/epidemiologia
6.
PLoS Med ; 16(5): e1002800, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31067237

RESUMO

BACKGROUND: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. METHODS AND FINDINGS: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. CONCLUSIONS: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02319525.


Assuntos
Técnicas de Apoio para a Decisão , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Educação de Pacientes como Assunto , Participação do Paciente , Adulto , Comportamento de Escolha , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/etnologia , Nefrite Lúpica/imunologia , Pessoa de Meia-Idade , Folhetos , Resultado do Tratamento , Estados Unidos/epidemiologia
7.
Nephrology (Carlton) ; 23 Suppl 4: 80-83, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30298658

RESUMO

Immunosuppressive therapies for lupus nephritis (LN) have improved significantly over the past few decades, resulting in growing number of choices for treatment individualization and improved renal and patient outcomes. Corticosteroids combined with mycophenolate or cyclophosphamide induces a satisfactory response in a high proportion of Asian and Caucasian patients, but the rate of improvement varies considerably between patients. Relatively low disease flare rate was observed in Chinese patients receiving low-dose prednisolone and mycophenolate maintenance. Short-term results with calcineurin inhibitors (CNI) are encouraging, attributed both to their immunosuppressive efficacy and the action of these agents on podocyte biology leading to more rapid proteinuria suppression. Additional data, especially on the avoidance of nephrotoxicity and metabolic side effects, is required to facilitate selection of patients appropriate for this treatment. Modifications of standard regimens such as reducing corticosteroid exposure or using enteric-coated mycophenolate might help reduce treatment-related toxicities without compromising efficacy. While clinical outcomes of patients have improved with recent therapeutic advances, individual and ethnic variations in disease manifestations and treatment response, as well as the prevention of infections and long-term complications still present challenges to frontline clinicians. Recent data from histological examination and translational studies also suggest that complement activation via the alternative pathway, immune deposition on renal tubular basement membrane, and local inflammatory responses involving resident kidney cells are of pathogenic relevance in LN. The progress of clinical and translational studies has improved not only the understanding of disease mechanisms but also clinical decision making in the management of LN.


Assuntos
Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Nefrite Lúpica/tratamento farmacológico , Animais , Quimioterapia Combinada , Humanos , Imunossupressores/efeitos adversos , Rim/imunologia , Rim/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Nefrite Lúpica/imunologia , Resultado do Tratamento
8.
Arthritis Res Ther ; 20(1): 193, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157968

RESUMO

BACKGROUND: Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. METHODS: TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan. The distributions of IFNL3/4 SNP genotypes and allele frequencies were compared between SLE patients and healthy controls and among SLE patients stratified by clinical phenotypes. ELISA was used to determine the serum IFN-λ3 concentrations of SLE patients. RESULTS: All major IFN3/4 SNP alleles were significantly associated with the risk for lupus nephritis (rs8099917T, PFDR = 0.0021, OR 1.75, 95% CI 1.24-2.47; rs12979860C, PFDR = 0.0034, OR 1.65, 95% CI 1.18-2.30; rs4803217C, PFDR = 0.0021, OR 1.76, 95% CI 1.25-2.48; and ss469415590TT, PFDR = 0.0021, OR 1.73, 95% CI 1.23-2.42) among SLE patients. Similarly, the major IFNL3/4 SNP haplotype rs8099917T-ss469415590TT-rs12979860C-rs4803217C (or T-TT-C-C) was a significant risk factor for lupus nephritis (P = 0.0015, OR 1.68, 95% CI 1.22-2.32). Additionally, all minor IFN3/4 SNP alleles were significantly associated with SLE susceptibility in nephritis-negative SLE patients as compared to normal healthy controls (rs8099917G, PFDR = 0.00177, OR 1.68, 95% CI 1.24-2.28; rs12979860T, PFDR = 0.00299, OR 1.58, 95% CI 1.18-2.32; rs4803217A, PFDR = 0.00176, OR 1.65, 95% CI 1.22-2.23; and ss469415590ΔG, PFDR = 0.00176, OR 1.70, 95% CI 1.26-2.29). Furthermore, the elevated serum levels of IFN-λ3 were significantly correlated with the complement depression and the high SLE disease activities in SLE patients. CONCLUSIONS: IFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE.


Assuntos
Predisposição Genética para Doença/genética , Interleucinas/genética , Nefrite Lúpica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/sangue , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Haplótipos , Humanos , Interferons , Interleucinas/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/sangue , Nefrite Lúpica/etnologia , Masculino , Pessoa de Meia-Idade , Taiwan , Adulto Jovem
9.
Yonsei Med J ; 59(7): 857-864, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30091319

RESUMO

PURPOSE: The aim of this study was to identify the associations among physical activity, disease activity, and organ damage in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: A total of 415 patients with SLE were consecutively enrolled from the KORean lupus Network (KORNET) registry. This registry assessed clinical features, disease activity [Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)], and organ damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI)] upon enrollment in the study. Self-reported physical activity was measured by the International Physical Activity Questionnaire. Statistical analyses were conducted using the Mann-Whitney U test and multivariate logistic regression analysis. RESULTS: A significant difference in vigorous activity was noted between patients with lupus nephritis (LN) (n=93) and those without LN (n=322) (p=0.012), but not in moderate and walking activities. In contrast, no differences in physical activity, walking, moderate, and vigorous intensity, according to SLEDAI-2K and SDI were found. In addition to younger age (p=0.032), high physical component summary of SF-36 (p=0.004) and SLEDAI-2K (p=0.038), and less vigorous physical activity were associated with LN (p=0.024). However, cardiovascular disease was not associated with physical activity in SLE patients. CONCLUSION: This study showed that patients with LN had less vigorous physical activity than patients without LN. The results suggest that lupus nephritis might be associated with physical activity.


Assuntos
Exercício Físico , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/etnologia , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-Idade , Sistema de Registros , República da Coreia/epidemiologia , Autorrelato , Índice de Gravidade de Doença
10.
Arthritis Res Ther ; 20(1): 152, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053827

RESUMO

BACKGROUND: The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). METHODS: We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504). Samples from systemic sclerosis patients (n = 99) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n = 656). RESULTS: Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score. CONCLUSIONS: Our sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte-macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in clinical trials.


Assuntos
Biomarcadores/sangue , Interferon-alfa/biossíntese , Lúpus Eritematoso Sistêmico/sangue , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/sangue , Adulto , Idoso , Feminino , Humanos , Imunoensaio/métodos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/sangue , Nefrite Lúpica/etnologia , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Transcriptoma , Adulto Jovem
11.
PLoS One ; 13(6): e0199003, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29953444

RESUMO

OBJECTIVE: African Americans, East Asians, and Hispanics with systemic lupus erythematous (SLE) are more likely to develop lupus nephritis (LN) than are SLE patients of European descent. The etiology of this difference is not clear, and this study was undertaken to investigate how genetic variants might explain this effect. METHODS: In this cross-sectional study, 1244 SLE patients from multiethnic case collections were genotyped for 817,810 single-nucleotide polymorphisms (SNPs) across the genome. Continental genetic ancestry was estimated utilizing the program ADMIXTURE. Gene-based testing and pathway analysis was performed within each ethnic group and meta-analyzed across ethnicities. We also performed candidate SNP association tests with SNPs previously established as risk alleles for SLE, LN, and chronic kidney disease (CKD). Association testing and logistic regression models were performed with LN as the outcome, adjusted for continental ancestries, sex, disease duration, and age. RESULTS: We studied 255 North European, 263 South European, 238 Hispanic, 224 African American and 264 East Asian SLE patients, of whom 606 had LN (48.7%). In genome-wide gene-based and candidate SNP analyses, we found distinct genes, pathways and established risk SNPs associated with LN for each ethnic group. Gene-based analyses showed significant associations between variation in ZNF546 (p = 1.0E-06), TRIM15 (p = 1.0E-06), and TRIMI0 (p = 1.0E-06) and LN among South Europeans, and TTC34 (p = 8.0E-06) was significantly associated with LN among Hispanics. The SNP rs8091180 in NFATC1 was associated with LN (OR 1.43, p = 3.3E-04) in the candidate SNP meta-analysis with the highest OR among African-Americans (OR 2.17, p = 0.0035). CONCLUSION: Distinct genetic factors are associated with the risk of LN in SLE patients of different ethnicities. CKD risk alleles may play a role in the development of LN in addition to SLE-associated risk variants. These findings may further explain the clinical heterogeneity of LN risk and response to therapy observed between different ethnic groups.


Assuntos
Nefrite Lúpica/etnologia , Nefrite Lúpica/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Coortes , Feminino , Humanos , Nefrite Lúpica/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Lupus ; 27(7): 1207-1217, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29665754

RESUMO

There are varying observations on the influence of ethnicity on the clinical spectrum and response to treatment in lupus nephritis (LN). We studied a multiethnic South African LN cohort to determine the clinical manifestations, histological involvement and response to therapy. We reviewed the records of LN patients at Inkosi Albert Luthuli Central Hospital in Durban. There were 105 patients, 92.5% females and they comprised 49.1% Indians and 45.3% African Blacks. The mean age was 31.3 ± 12.5 years, and 41.5% had LN at first presentation of lupus. The most common histological classes were Class V alone in 34.9%, Class IV (± Class V) in 25.5% and Class III (±Class V) in 22.6%. The estimated glomerular filtration rate was reduced (<30 ml/min) at presentation in 15 (14.2%). Eighty-seven patients received therapy for LN. A response to induction therapy was noted in 81.6% and maintenance therapy (12 months) in 73.6%. Response to mycophenolate mofetil (MMF) was 80.4% and 68.4% during induction and maintenance therapy, respectively. There was no ethnic difference in the histological class or response to MMF but African Blacks had more severe renal disease at presentation. In conclusion, our multiethnic LN cohort shows a high prevalence of membranous LN and good response to treatment.


Assuntos
Nefrite Lúpica/complicações , Nefrite Lúpica/tratamento farmacológico , Adulto , Grupo com Ancestrais do Continente Africano , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Índia , Nefrite Lúpica/etnologia , Masculino , Ácido Micofenólico/uso terapêutico , África do Sul
13.
Lupus ; 27(8): 1387-1392, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29703123

RESUMO

Objective To study the influence of Maghrebian ethnicity on lupus nephritis. Methods We retrospectively reviewed the files of a cohort of 194 patients with proliferative lupus nephritis followed in seven lupus centres belonging to three groups: Europeans living in Belgium/France (E; n = 111); Maghrebians living in Europe, in casu Belgium/France (ME; n = 43); and Maghrebians living in Morocco (MM; n = 40). Baseline presentation was compared between these three groups but complete long-term outcome data were available only for E and ME patients. Results At presentation, the clinical and pathological characteristics of lupus nephritis did not differ between E, ME and MM patients. Renal relapses were more common in ME patients (54%) than in E patients (29%) ( P < 0.01). Time to renal flare and to end-stage renal disease was shorter in ME patients compared to E patients ( P < 0.0001 and P < 0.05, respectively). While proteinuria measured at month 12 accurately predicted a serum creatinine value of less than 1 mg/dl at 7 years in E patients, this was not the case in the ME group, in whom serum creatinine at month 12 performed better. Conclusion Despite a similar disease profile at onset, the prognosis of lupus nephritis is more severe in Maghrebians living in Europe compared to native Europeans, with a higher relapse rate.


Assuntos
Imunossupressores/uso terapêutico , Falência Renal Crônica/mortalidade , Rim/patologia , Nefrite Lúpica/tratamento farmacológico , Proteinúria/etnologia , Adulto , África do Norte/etnologia , Creatinina/sangue , Europa (Continente) , Feminino , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/etnologia , Nefrite Lúpica/complicações , Nefrite Lúpica/etnologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Lupus ; 27(2): 257-264, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28728507

RESUMO

Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lupus erythematosus (SLE) and LupusPRO were compared, stratified by (a) presence of LN (ACR classification criteria (ACR-LN)) at any time and, (b) active LN (on SLEDAI) at study visit. Damage was assessed by SLICC/ACR-SDI. Multivariate regression analyses for QOL against ACR-LN (active LN) after adjusting for age, gender, ethnicity and country of recruitment were performed. Results Mean (SD) age was 41.7 (13.5) yrs, 93% were women. Five hundred and thirty-nine of 1259 SLE patients had ACR-LN. ACR-LN group was younger, were more often on immunosuppressive medications, had worse QOL on lupus medications and procreation than non-ACR-LN patients. HRQOL and non-HRQOL scores were similar in both groups. One hundred and twenty-nine of 539 ACR-LN patients had active LN. Active LN group was younger, had greater disease activity and had worse HRQOL and non-HRQOL compared to patients without active LN. Specific domains adversely affected were lupus symptoms, lupus medications, procreation, emotional health, body image and desires-goals domains. Patients with ACR-LN and active LN fared significantly worse in lupus medications and procreation HRQOL domains, even after adjusting for age, ethnicity, gender and country of recruitment. Conclusions Lupus nephritis patients have poor QOL. Patients with active LN have worse HRQOL and non-HRQOL. Most domains affected are not included in the generic QOL tools used in SLE. LN patients must receive discussion on lupus medications and procreation issues. Patients with active LN need comprehensive assessments and addressal of QOL, along with treatment for active LN.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Nefrite Lúpica/classificação , Nefrite Lúpica/psicologia , Qualidade de Vida/psicologia , Adulto , Imagem Corporal/psicologia , Estudos Transversais , Emoções/fisiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etnologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença
15.
Int J Rheum Dis ; 21(1): 194-199, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28762647

RESUMO

BACKGROUND: Lupus nephritis (LN) is a feared complication of systemic lupus erythematosus (SLE). Renal biopsy is valuable to assess disease severity and prognosis, but no histological data are available for Indigenous Australians (IA). We compared histopathology between IA and non-IA patients (NI) with LN in northern Australia and describe main outcomes. METHODS: Retrospective cohort study of all patients with biopsy evidence of LN at Royal Darwin Hospital over a 10-year period. Biopsies were classified by International Society of Nephrology criteria with clinical finding and vital status obtained from electronic health records. Data analyses used Australian Bureau of Statistics 2011 census population, nonparametric testing and lifetable estimates. RESULTS: The study cohort contained 42 patients (mean age 30 years,86% female and 74% IA). The estimated annual incidence of biopsy-proven LN was 7/100 000 for IA versus 0.7/100 000 for NI (P < 0.01). More IA patients had full-house immune complex deposition (79% vs. 21%, P < 0.05), but fewer IA patients had proliferative LN (classes III + IV) (42% vs. 72%) (P < 0.01). Five and 10-year patient (69% and 50%) and renal survival (87% and 53%) in IA were much worse than for NI patients. The reported causes of death were infections (38.6%), end-stage renal disease (23%), cardiovascular events (15.4%). CONCLUSION: Indigenous Australians more frequently have histological evidence of LN with a broader spectrum of immune complex deposition but less severe renal inflammation compared to non-Indigenous patients. The relative contribution of LN to reduced patient and renal survival for Indigenous Australians thus requires further study.


Assuntos
Rim/patologia , Nefrite Lúpica/etnologia , Nefrite Lúpica/patologia , Grupo com Ancestrais Oceânicos , Adulto , Complexo Antígeno-Anticorpo/análise , Biópsia , Causas de Morte , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Rim/imunologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/mortalidade , Masculino , Northern Territory/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
16.
Lupus ; 27(4): 637-646, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29073812

RESUMO

Background Information regarding urinary biomarkers in Mestizo and Afro-Latin-American patients is very limited. We investigated whether levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus nephritis among Latin-American systemic lupus erythematosus (SLE) patients. Methods SLE patients meeting the revised American College of Rheumatology classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1 were measured using a commercial ELISA kit. Serum anti-C1q antibodies were measured by ELISA. SLE activity was measured with the systemic lupus erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations between continuous variables. In addition, receiver operating characteristic curves were performed. Results One hundred and twenty SLE patients were recruited (87% women) with a median age of 32.8 ± 12.1 years and median disease duration of 7.3 ± 6.9 years. Afro-Latin-Americans had a significantly higher prevalence of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers were significantly higher in patients with lupus nephritis than in patients without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly higher in patients with active lupus nephritis than in inactive lupus nephritis. Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A receiver operating characteristic curve for urinary biomarkers for lupus nephritis in all SLE patients showed a good level of sensitivity and specificity. Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in addition to anti-C1q antibodies were useful biomarkers for the identification of renal involvement and discrimination of active lupus nephritis among patients with renal disease.


Assuntos
Quimiocina CCL2/urina , Lipocalina-2/urina , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/urina , Adulto , Grupo com Ancestrais do Continente Africano , Autoanticorpos/sangue , Biomarcadores/sangue , Biomarcadores/urina , Colômbia/epidemiologia , Complemento C1q/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índios Sul-Americanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Nefrite Lúpica/etiologia , Masculino , Valor Preditivo dos Testes , Prevalência , Regulação para Cima , Urinálise/métodos , Adulto Jovem
17.
J Int Med Res ; 46(3): 1008-1014, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29207897

RESUMO

Objective To investigate the association of the CD11b single nucleotide polymorphism (SNP) rs1143679 with systemic lupus erythematosus (SLE) in Han Chinese patients, and to clarify this association with SLE clinical manifestations. Methods PCR-restriction fragment length polymorphism and direct sequencing of CD11b rs1143679 were conducted in 584 patients with SLE and 628 healthy controls in this case-control study to compare genotype and allele frequency distributions. Correlations between CD11b genotypes and clinical manifestations were also determined. Results The frequency of the CD11b rs1143679 GA genotype was 1.89% in Han Chinese patients with SLE, which was much lower than that of European and American populations, but close to the frequency observed in individuals from Hong Kong and Thailand. The CD11b rs1143679 GA genotype was also shown to confer susceptibility to SLE (odds ratio = 4.00, 95% confidence interval = 1.11-14.41). CD11b rs1143679 was found to be significantly associated with nephritis, but not with age of disease onset, arthritis, hematological involvement, or neural lesions. Conclusion CD11b rs1143679 appears to be associated with risk for SLE in the Han Chinese population, and may play an important role in the development of lupus nephritis.


Assuntos
Antígeno CD11b/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Frequência do Gene , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/etnologia , Nefrite Lúpica/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Análise de Sequência de DNA
18.
Int J Rheum Dis ; 20(12): 2053-2061, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28984075

RESUMO

OBJECTIVES: To identify the association of glucocorticoid receptor (GR) gene polymorphism with systemic lupus erythematosus (SLE). METHODS: A case-control study was carried out, in which 400 Chinese patients with SLE and 400 normal people were enrolled. DNA was extracted using a genomic DNA extraction kit, and tagged single nucleotide polymorphisms (SNPs) were identified by Haploview (4.0) Project from the Chinese HapMap Project. Eighteen tagged SNPs of the GR gene were genotyped by the Multiplex SNaPshot technique. RESULTS: Two GR gene SNPs were associated with the pathogenesis of SLE: rs6865292 (dominant model: crude odds ratio [OR] = 1.526, 95% CI: 1.151-2.025, P = 0.003; adjusted OR = 1.525, 95% CI: 1.149-2.023, P = 0.004; PBH = 0.036) and rs9324921 (dominant model: crude OR = 1.556, 95% CI: 1.173-2.062, P = 0.002; adjusted OR = 1.553, 95% CI: 1.171-2.060, P = 0.002; PBH = 0.036). The haplotype analysis of GR gene SNPs manifested that the haplotype of 'CCGGG' (OR = 2.701, 95% CI: 1.348-5.410, P = 0.004; PBH = 0.036) was a risk factor for the development of SLE. A lower frequency of A-allele of SNP rs4607376 (P = 0.021; OR = 0.794, 95% CI: 0.652-0.966, PBH = 0.126), higher frequency of C-allele of SNP rs6865292 (P = 0.019, OR = 1.317, PBH = 0.126) and A-allele of SNP rs9324921 (P = 0.019, OR = 1.317, PBH = 0.126) may be risk factors for developing SLE. The rs7719514 (recessive model: crude P = 0.044; adjusted P = 0.044, PBH = 0.264), rs7701443 (recessive model: crude P = 0.044, adjusted P = 0.045; PBH = 0.264), rs4607376 (recessive model: crude P = 0.027; adjusted P = 0.026; PBH = 0.264) and haplotype 'CAGCG' (P = 0.044; PBH = 0.198) showed marginal association with the pathogenesis of SLE. In the case group, there were no significant differences between non-lupus nephritis and lupus nephritis. Further, we found that the SNP rs12054797 (F = 3.228, P = 0.041, PBH = 0.342), rs2963156 (F = 3.163, P = 0.043, PBH = 0.342) might be marginally associated with disease activity. CONCLUSIONS: The study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of SLE.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Heterozigoto , Homozigoto , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Nefrite Lúpica/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Adulto Jovem
19.
Lupus ; 26(10): 1034-1041, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28420049

RESUMO

Objective The objective of this study was to examine neuropsychiatric lupus in a Black Caribbean population. Methods We reviewed Barbados National Lupus Registry patients with ≥4 American College of Rheumatology criteria and a diagnosis of neuropsychiatric lupus using the American College of Rheumatology 19 case definitions. Results From 366 patients with four or more American College of Rheumatology criteria for systemic lupus erythematosus, 55 (15%) had evidence of neuropsychiatric lupus. There were 51 females and four males (F:M = 13:1) with a median age of 31 years. A total of 76.4% had a single neuropsychiatric lupus complication and 23.6% had two or three complications occurring sequentially or concurrently. The top three complications were psychosis - 49.1% (95% CI 35.8, 62.5); ischaemic stroke - 32.7% (21.4, 46.5); and generalized tonic-clonic seizures - 12.7% (6.0, 24.8). Twelve of the American College of Rheumatology 19 neuropsychiatric syndromes were represented: 91.2% central; 8.8% peripheral. There were 521 observation years, and for 32 patients (58%) neuropsychiatric lupus was a presenting feature. For the remaining 23 (42%) the first neuropsychiatric lupus event came after systemic lupus erythematosus diagnosis - median time of two years. Of the 22 deaths, systemic lupus erythematosus nephritis caused almost half (45.5%) at a median age of 32. The prevalence of nephritis was lower in the neuropsychiatric lupus subgroup (25.5%) compared with the Barbados National Lupus Registry data (47%) ( P = 0.01). Ischaemic stroke caused 22.7% of deaths at a median age of 46 and was the main cause of chronic neurologic deficits amongst survivors. Conclusion Neuropsychiatric lupus was an early cause of morbidity in systemic lupus erythematosus with predominantly singular central nervous system complications, the most common of which was psychosis. Most deaths occurred at a young age, principally from systemic lupus erythematosus nephritis. Ischaemic stroke was the main neurologic cause of death and disability.


Assuntos
Grupo com Ancestrais do Continente Africano , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Adulto , Barbados/epidemiologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etnologia , Isquemia Encefálica/etiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etnologia , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etnologia , Transtornos Psicóticos/etiologia , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/etiologia , Fatores de Tempo
20.
Cytokine ; 96: 189-194, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28433894

RESUMO

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder that affects multiple organs where exact etiology of the disease is not yet clearly understood. Various evidences suggest that genetic polymorphisms in inflammatory mediators like cytokines and chemokines may influence development of the disease. Here, we investigated whether functional polymorphism at the Monocyte Chemoattractant Protein-1 (MCP-1) regulatory region associates with disease phenotype in Indian SLE patients. This case control study included 200 SLE patients and 201 ethnically matched healthy controls. Genotyping of MCP-1 (-2518 A/G) polymorphism was performed using PCR-RFLP method. Serum MCP-1 levels were detected by bead-based multiplex immunoassay. Serum MCP-1 levels were found to be higher in patients compared with healthy individuals (p<0.0001). A significant difference for MCP-1G allele frequency (OR=1.9, 95%CI=1.4-2.6, p<0.0001) was observed among SLE patients against healthy individuals. A significant difference in the distribution of MCP-1 -2518GG (OR=3.0, 95%CI=1.4-6.7, p=0.0041) and AG+GG genotypes (OR=2.0, 95%CI=1.4-3.0, p=0.0005) was also noted among SLE patients when compared with healthy individuals. A significant association was observed between A/G and G/G versus A/A genotypes with renal manifestations (p<0.0001, Pc<0.001). Serum MCP-1 levels in active LN patients were found to be significantly higher than inactive LN (p=0.0059), mild LN (p=0.0061) as well as non-LN patients (p=0.0001). These findings suggest that -2518G allele of MCP-1 -2518 A/G polymorphism is associated with renal disorders and may influence MCP-1 gene expression among Indian SLE patients.


Assuntos
Quimiocina CCL2/genética , Predisposição Genética para Doença , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Feminino , Frequência do Gene , Genótipo , Humanos , Índia , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/etnologia , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Adulto Jovem
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