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Mycophenolate mofetil and rituximab have been shown to be considerably associated with poorer outcomes following SARS-CoV-2 infection. Such agents were associated with longer hospital stay as well as severe COVID-19 outcomes (infection-related complications, intensive care unit admission, and mortality). Using the data of the COVID-19 Global Rheumatology Alliance (GRA) registry of inflammatory rheumatic disease (IRD) patients in Kuwait, who had COVID-19 from March 2020 to March 2021, revealed 4 mortality cases (3 cases used CD-20 inhibitors as monotherapy and 1 case used mycophenolate mofetil/mycophenolic acid as monotherapy). This article describes the characteristics and course of disease among 4 patients with IRD who died following COVID-19 infection at Jaber Al Ahmed Hospital, Kuwait. The current series raises the intriguing prospect that IRD patients may have a varying risk of unfavorable clinical outcomes depending on the type of biological agents they were given. Rituximab and mycophenolate mofetil should be used with caution in IRD patients, particularly if they have concomitant comorbidities that put them at a high likelihood of developing severe COVID-19 outcomes.
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COVID-19 , Doenças Reumáticas , Reumatologia , Humanos , COVID-19/complicações , Rituximab/efeitos adversos , Ácido Micofenólico/uso terapêutico , Kuweit/epidemiologia , SARS-CoV-2 , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Sistema de RegistrosRESUMO
Background: An association between serum uric acid (UA) and disease activity in rheumatoid arthritis (RA) patients has not been well studied. We describe RA patients with high and normal UA and study its association with RA activity. Methods: Adult RA patients from the Kuwait Registry for Rheumatic Diseases (KRRD) were studied from February 2012 through March 2022. Patients with documented UA levels were included. UA of >357 µmol/L (6mg/dL) was considered high. Statistical comparison and correlation were made using multivariate logistic regression. Results: Overall, 1054 patients with documented UA. A total of 158 patients (15%) had high UA level with a mean of 409± 44.4µmol/L. The mean age for the high UA group and low UA group were 59.3 ± 10.7 years and 54.5 ± 12.4 years, respectively (p<0.001). 49.4% were female in high UA group, and 62.2% were female in low UA group, respectively (p<0.05). Logistic analysis showed an inverse relation between DAS28 and UA, as lower DAS28 score was associated with higher UA level (p=0.032) OR 1.39. There was a direct relation with HAQ, creatinine and UA. A higher HAQ is associated with a higher UA level (p=0.019) OR 0.78. High creatinine level is also associated with high UA level (p<0.001) OR 0.24. The use of antirheumatic drugs was similar among patients with high and normal UA. Conclusion: RA patients with a higher UA had a lower disease activity despite using similar antirheumatic drugs. The reasons behind this association need to be further studied.
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BACKGROUND: Rheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity. OBJECTIVE: The present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA. METHODS: Adult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross-sectional study conducted on 754 RA patients visits aged (21-79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14-item Questionnaire (paper or web-based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity. RESULTS: The finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28 < 3.2, DAS28 ≥ 3.2), several Mediterranean survey components showed statistically significant differences. Patients with a Mediterranean score ≤ 5 was more likely to have hazard effects for DAS28 than those with a Mediterranean score of ≥10 (HR = 0.17, CI [0.08-0.37], p < .001). The finding shows that, Mediterranean levels ≤5, on biologics treatment, CRP, and patient global assessment were significantly associated with overall survival. Additionally, the MedDiet was found to be a significant predictor of DAS28 in the random forest decision tree plot, along with tender, RF, and creatinine. MedDiet patients had a lower DAS28 score than others. CONCLUSION: The findings suggest that optimal drug treatment and a restrictive diet can help to improve DAS28 score for patients with RA. More patients in the cohort DAS28 <3.2 used olive oil, servings of vegetables, fruits, and legumes. In contrast, more patients in the cohort DAS28 ≥ 3.2 consumed red meat, butter, sweetened or soft drinks, cakes, cookies, or biscuits, and tomato sauce.
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Artrite Reumatoide , Produtos Biológicos , Dieta Mediterrânea , Adulto , Humanos , Estudos Transversais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Articulações , Produtos Biológicos/uso terapêutico , Índice de Gravidade de DoençaRESUMO
There is a significant variation in symptoms and clinical presentation of connective tissue disorders (CTD) associated with interstitial lung disease (ILD) (CTD-ILD). This presents difficulties in the diagnosis and treatment of CTD-ILD. Early detection and treatment of CTD-ILD using a multidisciplinary approach have been shown to enhance patient outcomes. This exercise aims to explore clinical components to develop a screening tool for pulmonologists for early detection of CTD in ILD and to provide a framework for a multidisciplinary approach in managing CTD-ILD. This in turn will lead to early treatment of CTD-ILD in collaboration with rheumatologists. A panel of 12 leading rheumatologists from the Middle East and North Africa (MENA) region met virtually to select the most relevant clinical findings to aid in identifying CTD-ILD. Twelve panellists opted to investigate seven of the most common inflammatory autoimmune disorders. The panel discussed how to improve the early detection of CTD-ILD. Clinical characteristics were categorized, and a nine-item questionnaire was created. A biphasic algorithm was developed to guide early referral to a rheumatologist based on the presence of one of nine clinical features of CTD (Phase 1) or the presence of CTD-specific antibodies (Phase 2). A brief questionnaire has been developed to serve as a simple and practical screening tool for CTD-ILD detection. Additional research is needed to validate and evaluate the tool in longitudinal cohorts.
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PURPOSE: We aimed to assess the characteristics of inflammatory rheumatic disease (IRD) patients in Kuwait diagnosed with COVID-19 and the factors linked with hospitalization, complications, and mortality. METHODS: Data of IRD patients from Kuwait diagnosed with COVID-19 between March 2020 and March 2021, submitted to the COVID-19 Global Rheumatology Alliance physician-reported registry, were included in our analysis. Data on patients' age, gender, smoking, diagnosis, IRD activity, and other comorbidities were collected. Statistical Package for the Social Sciences (SPSS), version 25, was used for statistical analysis. RESULTS: A total of 52 patients were included, with a mean age of 55 years (±14). The majority of patients were ≤65 years (77%), female (77%), non-smokers (80.8%), and diagnosed with rheumatoid arthritis (67.0%). Of the included patients, 19.2%, 9.6%, and 7.7% reported having methotrexate monotherapy, antimalarials monotherapy, and interleukin-6 inhibitors monotherapy immediately before COVID-19, respectively. Most of the included patients (92.3%) were either in remission or had minimal/low disease activity, while others (7.7%) had moderate disease activity. Forty-three patients (82.7%) were hospitalized, while 11 patients (25.6%) required ventilation (invasive or non-invasive). Ten of the ventilated patients (90.9%) received glucocorticoids as part of the local protocol to treat severe COVID symptoms, and 4 patients (7.69%) died. The duration till symptom-free ranged between 0 to 30 days, with a mean value of 10 days (±6.5). CONCLUSION: The current study provides timely real-world evidence regarding characteristics and potential risk factors linked to poor COVID-19-related outcomes in the IRD population in Kuwait.
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Antirreumáticos , COVID-19 , Médicos , Doenças Reumáticas , Reumatologia , Antirreumáticos/efeitos adversos , COVID-19/epidemiologia , COVID-19/terapia , Feminino , Humanos , Kuweit/epidemiologia , Pessoa de Meia-Idade , Sistema de Registros , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , SARS-CoV-2RESUMO
The emergency state caused by COVID-19 saw the use of immunomodulators despite the absence of robust research. To date, the results of relatively few randomized controlled trials have been published, and methodological approaches are riddled with bias and heterogeneity. Anti-SARS-CoV-2 antibodies, convalescent plasma and the JAK inhibitor baricitinib have gained Emergency Use Authorizations and tentative recommendations for their use in clinical practice alone or in combination with other therapies. Anti-SARS-CoV-2 antibodies are predominating the management of non-hospitalized patients, while the inpatient setting is seeing the use of convalescent plasma, baricitinib, tofacitinib, tocilizumab, sarilumab, and corticosteroids, as applicable. Available clinical data also suggest the potential clinical benefit of the early administration of blood-derived products (e.g. convalescent plasma, non-SARS-CoV-2-specific immunoglobins) and the blockade of factors implicated in the hyperinflammatory state of severe COVID-19 (Interleukin 1 and 6; Janus Kinase). Immune therapies seem to have a protective effect and using immunomodulators alone or in combination with viral replication inhibitors and other treatment modalities might prevent progression into severe COVID-19 disease, cytokine storm and death. Future trials should address existing gaps and reshape the landscape of COVID-19 management.
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COVID-19 , COVID-19/terapia , Humanos , Imunização Passiva , Fatores Imunológicos/uso terapêutico , Pandemias , SARS-CoV-2 , Soroterapia para COVID-19RESUMO
The Kuwait Association of Rheumatology members met thrice in April 2020 to quickly address and support local practitioners treating rheumatic disease in Kuwait and the Gulf region during the coronavirus disease 2019 (COVID-19) pandemic. Because patients with rheumatic and musculoskeletal disease (RMD) may need treatment modifications during the COVID-19 pandemic, we voted online for the general guidance needed by local practitioners. In this review, we have addressed patients' vulnerability with rheumatic disease and issues associated with their optimum management. Our recommendations were based on the formulation of national/international guidelines and expert consensus among KAR members in the context of the Kuwaiti healthcare system for patients with RMD. The most recent reports from the World Health Organization, the Center for Disease Control, the National Institutes of Health-National Medical Library, and the COVID-19 educational website of the United Kingdom National Health Service have been incorporated. We discuss the management of RMD in various clinical scenarios: screening protocols in an infusion clinic, medication protocols for stable patients, and care for patients with suspected or confirmed COVID infection and whether they are stable, in a disease flare or newly diagnosed. Further, we outline the conditions for the hospital admission. This guidance is for the specialist and non-specialist readership and should be considered interim as the virus is relatively new, and we rely on the experience and necessity more than evidence collection. The guidance presented should be supplemented with recent scientific evidence wherever applicable.
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Artrite Reumatoide , COVID-19 , Doenças Musculoesqueléticas , Médicos , Doenças Reumáticas , Reumatologia , Humanos , Kuweit/epidemiologia , Pandemias/prevenção & controle , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Medicina EstatalRESUMO
OBJECTIVE: Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or patients with contraindications to cDMARDs or poor prognostic factors. The purpose of this study was to compare the prescription rates of biologics in Kuwaiti and non-Kuwaiti patients and to assess whether this had an impact on disease activity and quality of life in RA patients. METHODS: Data were extracted from the Kuwait Registry for Rheumatic Diseases. Adult patients who satisfied the ACR classification criteria for RA from four major hospitals in Kuwait were evaluated from February 2013 through May 2018. The treatment agents, disease activity, and quality of life of Kuwaiti patients were compared with non-Kuwaiti patients. RESULTS: A total of 1651 RA patients were included; 806 (48.8%) were Kuwaiti patients. Among Kuwaiti patients, 62.5% were on biologic drugs in comparison with 14% of non-Kuwaiti patients. In comparison with non-Kuwaiti patients, Kuwaiti patients had significantly lower numbers of swollen joints (p < 0.001) and disease activity score-28 scores (p = 0.02) and less steroid use (p < 0.001) yet a significantly higher health assessment questionnaire-disability index (p < 0.001). Regression analysis showed that DAS-28 scores were significantly associated with the treatment type (p < 0.001) and that nationality was significantly predictive of the treatment type (p < 0.001). CONCLUSION: In the setting of easy accessibility to treatment for Kuwaiti patients, biologics were prescribed by rheumatologists at a higher rate than for non-Kuwaitis. This may explain the lower disease activity and the lower rate of steroid use in Kuwaiti patients than non-Kuwaitis. KEY POINTS: ⢠Significant discrepancies in the rates of prescribing biologic therapies between KP and NKP in Kuwait were observed. ⢠Several treatment outcomes were significantly better in the KP group than in the NKP group even after adjustment of confounding factors. ⢠The poor access to biologic therapies was suggested to limit the effectiveness of RA treatments in the NKP group.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Humanos , Kuweit/epidemiologia , Qualidade de VidaRESUMO
OBJECTIVE: In 2016, ASAS and EULAR made joint recommendations for the management of patients with spondyloarthritis. Although Global and European perspectives are important, they cannot accurately reflect the situation for all patients in all countries and regions. As such, the group worked to tailor the existing international recommendations to suit the specific demographic needs of local populations in the Gulf region, with a specific focus on Kuwait. METHODS: Recommendations drafted following a PubMed search for relevant literature were reviewed and then underwent Delphi vote to reach consensus on those to be included. Advice for newly approved agents, including targeted synthetic disease-modifying anti-rheumatic drugs, was included based on the group's clinical experience. RESULTS: The resulting 41 recommendations are grouped into five categories covering key definitions and principles for the management and treatment of both axial and peripheral forms of spondyloarthritis. CONCLUSION: Through adaptation of existing guidelines and incorporating the current evidence and clinical experience of the members of the group, these recommendations have been developed to reflect the unique situation in Kuwait with regard to differing patient profiles, local culture and approved therapeutic approaches, and are designed to aid in clinical decision-making.
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The Kuwait Association of Rheumatology (KAR) aimed to develop a set of recommendations for the treatment of patients with rheumatoid arthritis (RA), tailored to the unique patient population and healthcare system of Kuwait. Each recommendation was developed based on expert opinion and evaluation of clinical practice guidelines from other international and national rheumatology societies. Online surveys were conducted to collate feedback on each KAR member's level of agreement (LoA) with definitions of disease-/treatment-related terms used and the draft recommendations. Definitions/recommendations achieving a pre-defined cut-off value of ≥ 70% agreement were accepted for inclusion. Remaining statements were discussed and revised at a face-to-face meeting, with further modifications until consensus was reached. A final online survey was used to collect feedback on each KAR member's LoA with the final set of recommendation statements on a scale of 0 (complete disagreement) to 10 (complete agreement). Group consensus was achieved on 66 recommendation statements, including 3 overarching principles addressing the pharmacological treatment and management of RA. Recommendations focused on treatment of early RA, established RA, patients with high-risk comorbidities, women during pregnancy and breastfeeding, and screening and treatment of opportunistic infections. The KAR 2018 Treatment Recommendations for RA reported here are based on a synthesis of other national/international guidelines, supporting literature, and expert consensus considering the Kuwaiti healthcare system and RA patient population. These recommendations aim to inform the clinical decisions of rheumatologists treating patients in Kuwait, and to promote best practices, enhance alignment and improve the treatment experience for patients.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Reumatologia/normas , Algoritmos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Medicina Baseada em Evidências/normas , Feminino , Humanos , Kuweit/epidemiologia , Masculino , Seleção de Pacientes , GravidezRESUMO
People with IRD are at increased risk of infection, and in 2011 EULAR made general recommendations for vaccination in these patients. Global and European perspectives are important, but they cannot accurately reflect the individual situations of patients in different countries and regions. Based on our clinical experience and opinions, we have sought to tailor the original EULAR recommendations to include advice for vaccination with new agents approved in the intervening years-including the new class of targeted synthetic disease-modifying antirheumatic drugs. We have also considered the specific demographic needs of patients in local populations in the Gulf region. The resulting 16 recommendations are grouped into four main categories covering general vaccination guidelines and best-practice for all patients with IRD, followed by a set of recommended vaccines against specific pathogens. The last two categories include recommendations for certain patient subgroups with defined risks and for patients who wish to travel.
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OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients with rheumatoid arthritis (RA) and to compare their features with those of patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were evaluated for RN. Demographic and serological features and disease activity and severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22 (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and family history of an autoimmune rheumatic disease were similar. Obesity was more prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs. 152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3 ± 2.9 vs. 2 ± 2.7, p < 0.001), more tender joints (6.4 ± 8.8 vs. 4.2 ± 7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 ± 2.7 vs. 2.3 ± 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74 (8%), p = 0.034. The mean health assessment questionnaire score in RN patients was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low disease activity (means: disease activity score [DAS-28], 3.02; clinical disease activity index, 7.7; and simple disease activity index, 10.4), similar to the other group. While the rates of methotrexate treatment were comparable, biologic therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478 [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA patients. Patients with and without RN are similar in terms of demographics and serologic features, except for more obesity. However, patients with RN have more sicca symptoms, joint deformities, and painful and tender joints. Disease activity scores are low with more frequent biologic therapy.
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Artrite Reumatoide/epidemiologia , Nódulo Reumático/epidemiologia , Adulto , Fatores Etários , Idade de Início , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Predisposição Genética para Doença , Nível de Saúde , Humanos , Kuweit/epidemiologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/epidemiologiaRESUMO
AIM: The present study aimed to identify the genes involved in the pathogenesis of systemic lupus erythematosus (SLE) in Arabs by investigating a panel of 84 genes related to the t helper (Th)17-related regulatory network and to further explore the expression levels of serum interleukin (IL)-17A and IL-17F in a studied cohort. A comparative analysis of gene expression profile in SLE and lupus nephritis (LN) patients against that of healthy controls (HC) was performed. METHOD: A quantitative real-time polymerase chain reaction (PCR) (Th17 autoimmunity and inflammation) array analysis was performed in peripheral white blood cells of 66 SLE patients under specific medical treatment and 30 age/gender/ethnically matched healthy controls. Statistical analysis was carried out using the RT(2) Profiler TM PCR Data Analysis tool. RESULTS: The analysis of Th17 pathway revealed 14 genes (IL-17A, IL-17C, IL-17D, IL-17F, IL-18, IL-12RB2, IL-23R, CCL2, CCL20, CXCL5, MMP3, RORC, STAT4 and TRAF6) that are differentially expressed in SLE and HC (fold change [FC] < 2, P < 0.0006). No significant difference in expression profiles was observed between SLE and LN. A significant difference in serum concentration of IL-17A (P = 0.002) and IL-17F (P = 0.002) was observed between SLE (13.91 ± 4.25) and LN (18.26 ± 4.24). CONCLUSION: Our study is the first to investigate a panel of 84 genes related to Th17 regulatory pathway in Arab SLE subjects and the first to explore the effect of current immunosuppression regimens on Th17 regulatory pathway. It paves the way for understanding the etiology of SLE and autoimmune diseases in general.
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Redes Reguladoras de Genes , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Células Th17/imunologia , Adolescente , Adulto , Árabes/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica/métodos , Estudos de Associação Genética , Humanos , Imunossupressores/uso terapêutico , Interleucina-17/sangue , Interleucina-17/imunologia , Kuweit , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Systemic lupus erythematosus (lupus) is an autoimmune disease characterized by multiorgan pathology, accelerated apoptosis and hyper-autoantibody production against self-components. The root cause of lupus remains unknown, although multiple susceptibility factors have been reported in different ethnic group. OBJECTIVE: We aimed to explore the genome-wide differential expression spectrum of lupus and its severe form lupus nephritis (LN) in Arab females. METHODS: A total of 98 subjects: 40 lupus, 18 LN and 40 age/gender/ethnically matched healthy controls (HC) were recruited. Carefully chosen subjects (n = 11) were employed for whole human-genome expression profiling using high-density Human Exon 1.0.ST arrays (Affymetrix) and statistical analysis was carried out using appropriate software. Validation cohorts (n = 98) were investigated to quantify the expression of the nine selected candidate genes relative to GAPDH as endogenous control. RESULTS: Genome-wide differential analysis revealed seven candidate genes in lupus and 36 in LN, when individually compared to HC (anova Welch t-test, P ≤ 0.005, Tukey's honestly post hoc analysis). Analysis of differentially expressed genes with a fold change of 2, revealed 16 Gene Ontology terms satisfying a P ≤ 0.05. We further detected five distinct inflammatory and metabolic pathways such as TWEAK, osteopontin, endochondral ossification, fluropyrimidine activity and urea cycle and metabolism of amino groups that significantly contribute to the pathogenesis of lupus (P < 0.05). Validation of selected candidate genes (IRF9, ABCA1, APOBEC3, CEACAM3, OSCAR, TNFA1P6, MMP9, SLC4A1) revealed significant differences in expression, indicating their promissory role in the pathogenesis of lupus. CONCLUSION: Our study provides central gene regulators of therapeutic potential, indicating the future prospects of the study.
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Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Adulto , Árabes/genética , Feminino , Perfilação da Expressão Gênica/métodos , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Kuweit/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
Systemic lupus erythematosus (lupus) is a genetically heterogeneous autoimmune disorder with an obscure etiology. With 92-94% of human genes exhibiting alternative splicing, gaining insights to such events may lead to better diagnostics. Herein, we explored the genome-wide peripheral blood transcriptome of lupus and its severe form lupus-nephritis (LN) compared to healthy controls (HC). Age/gender/ethnically-matched Arab females were tested using high-density arrays and statistical analysis was carried out using appropriate software. Analysis revealed 15 splice variants that are differentially expressed between lupus/HC and 99 variants between LN/HC (p ≤ 0.05, SI> or ≤ 0.5, Benjamin Hochberg-False discovery rate correction). Comparison between LN/lupus revealed 7 variants that significantly differed in expression. Pathway analysis of differentially spliced-genes postulated 11 significant pathways in lupus and 12 in LN (p<0.05). Analysis of peripheral blood transcriptome possibly revealed signature causative genes that are alternatively spliced, signifying their clinical relevance. Present study is the first to reveal the significance of alternative variants in lupus and LN.
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Nefrite Lúpica/genética , Transcriptoma , Árabes , Feminino , Humanos , Nefrite Lúpica/sangueRESUMO
The purpose of this study was to analyze the effect of the HumDN1 VNTR polymorphism on DNASE1 mRNA expression and enzyme activity in lupus (SLE) and rheumatoid arthritis (RA) compared to healthy control (HC). Kuwait subjects (n = 500) matched by age/gender/ethnicity were genotyped by fragment-analysis. DNASE1 expression was analysed using quantitative Real-Time-PCR and sera from subjects were screened for DNase1 reduction activity by ELISA. Allele and genotype distribution of HumDN1 VNTR revealed a significant association with susceptibility to SLE and RA (p < 0.05, OR > 1). Relative expression analysis revealed a significant increase in DNASE1 mRNA in SLE (p = 0.0001) and RA (p = 0.002) compared to HC. Stratification of subjects revealed, increased DNASE1 expression in SLE with 5/5 (p = 0.0001), 3/4 (p = 0.0001) and 3/5 genotype (p = 0.01). A reduction in DNASE1 expression was specifically observed in SLE with 4,4 genotype (p = 0.0004). RA patients with 3/4 genotype (p = 0.02) showed a significant increase in DNASE1 expression. Similarly a significant association was observed between DNase1 reduction activity and SLE (p = 0.0001). SLE patients with 3,4 (p = 0.0001) and 5,5 genotype (p = 0.0001) showed increased DNase1 reduction activity, while a lack of association was observed with RA. The present study is the first to reveal the effect of HumDN1 VNTR on DNASE1 expression in SLE and RA.
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Artrite Reumatoide/genética , Desoxirribonuclease I/genética , Regulação da Expressão Gênica , Lúpus Eritematoso Sistêmico/genética , Repetições Minissatélites , Polimorfismo Genético , Adulto , Idoso , Alelos , Artrite Reumatoide/metabolismo , Estudos de Casos e Controles , Desoxirribonuclease I/metabolismo , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To test the interrater and intrarater reliability of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Responder Index (SRI-50), an index designed to measure ≥ 50% improvement in disease activity between visits in patients with systemic lupus erythematosus. METHODS: This was a multicenter, cross-sectional study with raters from Canada, the United Kingdom, and Argentina. Patient profile scenarios were derived from real adult patients. Ten rheumatologists from university and community hospitals and postdoctoral rheumatology fellows participated. An SRI-50 data retrieval form was used. Each rheumatologist scored SLEDAI-2K at the baseline visit and SRI-50 on followup visit, for the same patients, on 2 occasions 2 weeks apart. Physician global assessment (PGA) was determined on a numerical scale at baseline visit and a Likert scale on followup visit. Interrater and intrarater reliability was assessed using intraclass correlation coefficient (ICC) and kappa statistics whenever applicable. RESULTS: Forty patient profiles were created. The ICC performed on 80 patient profiles for interrater ranged from 1.00 for SLEDAI-2K and SRI-50 to 0.96 for PGA. The intrarater ICC for SLEDAI-2K, SRI-50, and PGA scores ranged from 1.00 to 0.86. Substantial agreement was determined for the interrater Likert scale, with a kappa statistic of 0.57. CONCLUSION: The SRI-50 is reliable to assess ≥ 50% improvement in lupus disease activity. Use of the SRI-50 data retrieval form is essential to ensure optimal performance of the SRI-50. SRI-50 can be used by both rheumatologists and trainees and performs equally well in trained as well as untrained rheumatologists.