Indian Systemic Lupus Erythematosus Patients Research Articles

Identification and stratification of systemic lupus erythematosus patients into two transcriptionally distinct clusters based on IFN-I signature.

Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.

Cytokine genes multi-locus analysis reveals synergistic influence on genetic susceptibility in Indian SLE – A multifactor-dimensionality reduction approach

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear etiology. Several loci associated with genetic susceptibility for lupus have been described. However, it lacks reports on cytokine gene-gene interactions among SLE patients from Asian population. Epistasis interaction among single nucleotide polymorphisms (SNPs) of cytokine genes in Indian SLE patients was tested using multifactor-dimensionality reduction (MDR) analysis. A total of fourteen SNPs lacking linkage disequilibrium among different cytokines genes were genotyped in a cohort of 200 SLE patients and 201 healthy individuals as controls of Indian origin. A high degree of synergism among Lymphotoxin-α (LT-α), Interleukin-1β (IL-1β) and Interleukin-10 (IL-10) gene polymorphisms was detected in our SLE patients. Furthermore, by virtue of biological inter-relations among different cytokines, a high strength of interactions was observed among pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokine gene SNPs. Also, among studied pro-inflammatory cytokines and chemokines, a strong synergistic effect among Tumor Necrosis Factor-α (TNF-α), LT-α and Monocyte Chemo-attractant Protein-1 (MCP-1) SNPs was occurred. A nature of strong interaction among the candidate cytokine genes may speculate a proactive role in causing genetic susceptibility to the disease in SLE patients with Indian origin.

Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients.

Single nucleotide polymorphisms in cytokine genes including interleukin-10 have been described to play a vital role in the overall pathogenesis of systemic lupus erythematosus. However, due to a lack of evidence from the Indian population, this study was conducted to analyse the possible influence of interleukin-10 promoter polymorphisms over the disease susceptibility, serum interleukin-10 level and clinical manifestations of the disease in Indian systemic lupus erythematosus patients. In total, 200 systemic lupus erythematosus patients and 201 controls were recruited under this study. Genotyping of interleukin-10 (−1082A/G; −819T/C and −592C/A) polymorphisms was done by direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods respectively. Serum interleukin-10 levels were measured by multiplex assay. Interleukin-10 −1082G and −592A allele frequencies were significantly increased in systemic lupus erythematosus patients (corrected p value <0.05). Also, combined −1082AG+GG, −819TC+CC and −592CA+AA genotype frequencies were significantly increased in the patient group. A higher trend of association between −1082AG+GG genotype frequency was observed in patients with serositis (odds ratio = 2.7, p = 0.0233, corrected p value = 0.2097). Serum interleukin-10 levels were significantly higher in systemic lupus erythematosus patients (4.3 ± 3.1 pg/ml) than controls (2.6 ± 1.4 pg/ml) ( p < 0.0001). Furthermore, interleukin-10 levels were positively correlated with disease activity ( p = 0.39, p < 0.0001). The frequency of the GCA (−1082, −819, −592) haplotype was significantly higher in systemic lupus erythematosus patients (10.6%) than controls (1.6%) (odds ratio = 5.4, p = 0.0330). Moreover, ACC, GCC and GCA haplotypes were found to be strongly associated with serositis. However, the frequency of the ACC haplotype was significantly higher in patients with neurologic involvement (odds ratio = 14.9, corrected p value <0.001). Thus, interleukin-10 promoter polymorphisms suggest they have a proactive role in increased susceptibility to the disease among Indian systemic lupus erythematosus patients.

Occurrence, predictors and outcome of infections at three months in hospitalized patients with SLE: A prospective study from Southern India.

Prospective data on infections in systemic lupus erythematosus (SLE) from India are scarce. We studied the frequency and predictors of infections in hospitalized SLE patients. All data on infections were prospectively recorded. During the study period, 212 SLE patients (91% women) were hospitalised. Sixty-three (29.7%) had infections. The most common infections were pneumonia, skin and soft-tissue infections and urinary-tract infections. Mortality was higher in the infection group compared to the no infection group (11.1% vs. 0.7%; p=0.01). At three months, 10/63 developed another episode of infection. On logistic regression, the predictors of infection were fever [odds ratio (OR) = 4.17], vasculitis (OR = 2.64), thrombocytopaenia (OR = 3.59), presence of co-morbidities (OR = 3.59) and duration of hospital stay >11 days (OR = 3.55); p<0.001 for all. High-sensitivity CRP (hsCRP) and procalcitonin were measured in 95 patients. hsCRP was significantly higher in the infection group compared to the no infection group (median 27 vs. 6.5 mg/L; p<0.001). Procalcitonin was similar in both groups. A hsCRP of 11.5 mg/L had a sensitivity of 66.7% and specificity of 72.9% to diagnose infection. To conclude, 29.7% of Indian SLE patients who are hospitalized have infections, resulting in a significantly increased duration of hospital stay. The presence of fever and co-morbidities are predictors of infection. The role of high hsCRP to support the diagnosis of infection in SLE is once again confirmed.

Synergetic Interaction of HLA-DRB1*07 Allele and TNF-Alpha - 863 C/A Single Nucleotide Polymorphism in the Susceptibility to Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease which is characterized by dysregulation of various cytokines propagating the inflammatory processes that is responsible for tissue damage. Tumor necrosis factor alpha (TNF-α) is one of the most important immunoregulatory cytokines that has been implicated in the different autoimmune diseases including SLE. Two hundred and two patients with SLE and 318 controls were included in the study. The TNF-α gene promoter region (from - 250 to - 1000 base pairs) was analyzed by direct Sanger's DNA sequencing method to find promoter variants associated with South Indian SLE patients. We have analyzed six TNF-α genetic polymorphisms including, - 863C/A (rs1800630), - 857C/T (rs1799724), - 806C/T (rs4248158), - 646G/A (rs4248160), - 572A/C (rs4248161) and - 308G/A (rs1800629) in both SLE patients and controls. We did not find association of TNF-α gene promoter SNPs with SLE patients. However, the - 863A (rs1800630) allele showed association with lupus nephritis phenotype in patients with SLE (OR: 1.62, 95%CI 1.04-2.53, P = 0.034). We found serum TNF-α level was significantly elevated in SLE cases as compared to control and found no association with any of the polymorphisms. The haplotype analysis revealed a significant protective association between the wild TNF-α alleles at positions - 863C, - 857C, - 806C, - 646G, - 572A and - 308G (CCCGAG) haplotype with lupus nephritis phenotype (OR 0.53, 95% CI 0.35-0.82, P = 0.004). Additionally, the TNF-α - 863 C/A (rs1800630) polymorphism and HLA-DRB1*07 haplotype showed significant differences between SLE patients and controls (OR 4.79, 95% CI 1.73-13.29, P = 0.0009). In conclusion, TNF-α - 863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-α - 863 C/A promoter polymorphism giving supportive evidence for the tight linkage disequilibrium between TNF-α promoter SNPs and MHC class II DRB1 alleles.

Study of familial aggregation of autoimmune rheumatic diseases in Asian Indian patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases (AIRD) tend to co-aggregate in families, making positive familial history a risk factor. We aimed to estimate familial aggregation of AIRD in SLE patients and to compare between ones having a positive and negative family history of autoimmunity in our cohort. We included families of 157 consecutive SLE patients in a hospital-based, cross-sectional design for a three-generation pedigree study. Clinical and laboratory parameters of these patients were recorded. AIRD was seen in families of 39 SLE patients amounting to a familial prevalence of 24.8% [95% confidence interval (CI) 18.1, 31.6] with a relative risk (λ) of 4.3 for first-degree relatives (FDRs) and 1.1 for second-degree relatives (SDRs). SLE was the commonest AIRD seen in families of 19 patients with a familial prevalence of 12.1% (95% CI 7.0, 17.2) and λ of 78.2 for FDRs and 18.1 for SDRs. AIRD as a whole and SLE alone were seen more commonly with parental consanguinity (p < 0.05). Familial aggregation in SLE patientsalso showed a relatively higher percentage of affected males and lesser presentation with constitutional features (p < 0.05) than sporadic SLE patients. Rheumatoid arthritis (RA) was the second most common AIRD seen in 16/39 (41%) families with a RR of 3.1 in FDRs of SLE patients. In conclusion, Asian Indian SLE patients seem to havea high familial aggregation of AIRD, which is more pronounced in the background of parental consanguinity. SLE is the commonest AIRD seen amongst FDRs and SDRs of SLE patients, followed by RA, with FDRs being at highest risk.

Quality of life among female patients with systemic lupus erythematosus in remission.

The objective is to assess quality-of-life (QoL) parameters among Indian female systemic lupus erythematosus (SLE) patients with durable remission. Indian female SLE patients in remission determined by the European consensus criteria and age-matched female control participants were included in the study. All included participants underwent measurements of QoL [Medical Outcomes Study Short-Form-12 (SF12)], Fatigue Severity Scale, and structured interview with a clinical psychologist. The population comprised of 126 female SLE patients [median age: 27.5years [interquartile range (IQR): 11]; median disease duration: 36months (IQR 26)] and 110 female controls [median age 30years (IQR 9)]. Clinical remission was seen in 65.9% (83/126) and complete remission in 34.1% (43/126). Significant fatigue was present in 18.3% (23/126). Both SF-12 physical component summary (PCS) and mental component summary (MCS) were similar between SLE patients and controls [median PCS: 50.3 (IQR: 16.2) vs. 48.6 (IQR: 11.6); median MCS: 57.2 (IQR: 4.8) vs. 57.9 (IQR: 7.6)]. In generalised linear modelling, PCS was associated with fatigue [odd's ratio (OR) 0.012, 95% confidence interval (CI) 0.006-0.025, p < 0.001], disease duration ≥ 5years (OR 23.16, 95% CI 1.548-346.58, p = 0.023), and complete remission (OR 33.16, 95% CI 4.43-248.15, p = 0.001); MCS with fatigue (OR 0.53, 95% CI 0.34-0.84, p = 0.007) and absence of depression (OR 3.65, 95% CI 1.07-12.44, p = 0.038). Patients with SLE in remission report significant fatigue in 18.3% of subjects. Both PCS and MCS scores are similar to healthy controls. Better PCS was associated with less fatigue, longer disease duration, and complete remission. Better MCS was associated with less fatigue and absence of depression.

Impact of functional IL-18 polymorphisms on genetic predisposition and diverse clinical manifestations of the disease in Indian SLE patients.

Several studies have demonstrated associations between interleukin-18 polymorphisms and risk of systemic lupus erythematosus in different populations except one of Indian origin. We therefore investigated for the influence of interleukin-18 (-1297T/C, -607A/C, -137G/C; + 105A/C) polymorphisms on genetic susceptibility and clinical expression of the disease in Indian systemic lupus erythematosus patients. A total of 200 systemic lupus erythematosus patients and 201 controls were recruited. Genotyping of interleukin-18 polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. Serum interleukin-18 levels were measured by enzyme-linked immunosorbent assay. Interleukin-18 (-1297T/C; -137G/C) polymorphisms showed significant association with genetic susceptibility to the disease in our systemic lupus erythematosus cohort. Stratification analysis revealed -1297CC and -1297C associated with renal involvement (odds ratio = 3.4, correcting p value = 0.0207), (odds ratio = 2.0, correcting p value = 0.0054) respectively. Additionally, -1297C allele frequency was significantly increased in patients with anti-nucleosome antibody (odds ratio = 2.1, correcting p value = 0.0301). Haplotype analysis showed CC haplotype strongly associated with serositis (odds ratio = 9.1, correcting p values = 0.0009) and neurologic involvement (odds ratio = 9.3, correcting p value = 0.0018). We reported a 2.7-fold increase in serum interleukin-18 levels in patients (511.5 ± 242.3 pg/ml) compared to controls (189.4 ± 80.8 pg/ml) ( p < 0.0001). Furthermore, interleukin-18 levels were positively correlated with disease activity ( r = 0.548, p = 0.0001) and renal involvement in the patients with lupus nephritis ( r = 0.569, p < 0.0001). In summary, interleukin-18 polymorphisms elucidated in this study appear to confer genetic susceptibility to the disease and are associated with renal, serositis and neurologic involvement in Indian systemic lupus erythematosus patients.

The influence of functional polymorphic positions of HLA-DRβ1 molecules on risk for South Indian systemic lupus erythematosus patients.

The aim of this case-control study was to investigate the association of human leukocyte antigen (HLA) Class II alleles with the susceptibility and phenotypic heterogeneity in systemic lupus erythematosus (SLE) in South Indian patients. A total of 439 individuals (212 SLE cases and 227 age- and ethnicity-matched controls) were included in the study. The genotyping of HLA-DRβ1 and - DQβ1 was conducted by the PCR-SSP method. HLA-DRβ1*07 was significantly associated with SLE (OR: 2.02; 95% CI: 1.34-3.04, p = 1.50 × 10-4, pc = 1.95 × 10-3), whereas the DRβ1*14 allele was negatively associated with SLE (OR: 0.49; 95% CI: 0.31-0.76, p = 1.70 × 10-2, pc = 0.221). In addition, the HLA-DRβ1*07/15 genotype tended to be positively associated with SLE (OR: 3.23, 95% CI: 1.57-6.63, p = 0.0009). Amino acid residues residing in the peptide-binding pocket of HLA-DRβ1 play a significant role in peptide recruitment and antigen presentation. Our results demonstrated that amino acid glycine 11 (OR: 2.11, 95% CI: 1.42-3.12, pc = 0.00093), tyrosine 13 (OR: 2.11, 95% CI: 1.42-3.12, pc = 0.00062) and glutamine 74 (OR: 2.11, 95% CI: 1.42-3.12, pc = 0.00077) showed a significant positive association with SLE. Certain haplotype combinations, DRB1*07-DQβ1*03 (OR: 2.21; 95% CI:1.29-3.79, pc = 0.06, p = 0.00036) and DRβ1*07-DQβ1*05 (OR: 2.51, 95% CI: 1.34-4.71, pc = 0.07, p = 0.00039), had positive associations whereas DRβ1*14-DQβ1*03 (OR: 0.14, 95% CI: 0.061-0.36, pc = 2.34 × 10-5, p = 1.30 × 10-6) were found to have a significant negative association with SLE. So far, the present study is the first attempt to investigate the association of HLA-DRβ1 and - DQβ1 allele, genotype and haplotype combinations with the risk of SLE in South Indian patients. In conclusion, the HLA-DRβ1*07 allele is associated with risk of SLE whereas a protective association of HLA-DRβ1*14 alleles with SLE was observed.

The IRF5 rs2004640 (G/T) polymorphism is not a genetic risk factor for systemic lupus erythematosus in population from south India.

Background & objectives:Genetic aberrations disrupting toll-like receptor and interferon homeostasis enhance the risk of systemic lupus erythematosus (SLE). Raised serum interferon-alpha (IFN-α) levels in SLE patients have been ascribed to polymorphism (rs2004640 G/T) in interferon regulatory factor 5 (IRF5) gene, resulting in enhanced transcript splicing. A positive association between IRF5 polymorphism and SLE risk has been reported in many populations. This study was aimed to find out frequency of IRF5 rs2004640 G/T polymorphism in patients with SLE and healthy controls and to assess its influence on susceptibility, clinical and serological characteristics of SLE.Methods:IRF5 rs2004640 (G/T) polymorphism was analyzed in 300 SLE patients and 460 age and sex matched controls by real-time PCR.Results:The IRF5 rs2004640 (G/T) polymorphism did not confer risk of SLE or influence clinical or serological phenotype. However, the mutant allele conferred a borderline risk to develop thrombocytopenia (odds ratio: 2.05, 95% confidence interval: 0.97–4.3, P=0.06) in patients with SLE.Interpretation & conclusions:Our study revealed that the IRF5 rs2004640 polymorphism was not a risk factor for SLE in population from south India. It may, however, be a useful genetic marker for thrombocytopenia in SLE patients. Although we could not demonstrate susceptibility toward lupus in the presence of IRF5 rs2004640 (G/T) polymorphism, further exploration of the genetic variability of IRF5 may help uncover its pathogenic role in Indian SLE patients.

A functional SNP MCP-1 (−2518A/G) predispose to renal disorder in Indian Systemic Lupus Erythematosus patients

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.

Anti-C1q Antibody is Associated with Renal and Cutaneous Manifestations in Asian Indian Patients with Systemic Lupus Erythematosus.

C1q play an important role in clearance of immune complexes and apoptotic cell debris. Impaired clearance leads to exposure of C1 native antigen and development of anti-C1q antibody formation. Anti-C1q antibody is well studied in Systemic Lupus Erythematosus (SLE). Significance of anti-C1q Ab in Indian SLE patients and their clinical manifestations is not clear. The aim of this study was to investigate associations between anti-C1q antibody and clinical as well as serological markers of SLE. Retrospective study of SLE patients fulfilling either American College of Rheumatology (ACR) 1990 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria were recruited from inpatients and outpatients services of the Clinical immunology and Rheumatology Department, Christian Medical College at Vellore, India between March 2013 and January 2015. Anti-C1q antibody was assayed by ELISA (Demeditec Diagnostics GmbH, Germany). Logistic regression analysis was performed to find the association of anti-C1q antibodies with serological and clinical parameters in SLE including Lupus Nephritis (LN). Sixty nine patients (54.76%) out of 126 SLE patients had LN. Anti-C1q levels were higher in patients with LN as compared to those without (p<0.05). Anti-C1q antibody was also significantly associated with positive C1q immunofluorescence staining in renal biopsy specimens (p<0.05). Overall, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) {OR 1.35 (1.08-1.69)}, low C4 {OR 3.11 (1.04-9.26)} and mucocutaneous manifestation {OR 4.72 (1.38-16.05)} were independently associated with anti-C1q levels in serum. Renal SLEDAI, low C4 and mucocutaneous manifestations were independently associated with raised anti C1q antibody in SLE patients.

Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients

The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (−308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α −308A (OR=2.3, p=0.0001, Pc=0.0003) and LTα +252G (OR=2.1, p<0.0001, Pc<0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR=12.2, p=0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles. TNF-α −308G/A+A/A genotypes (p<0.01) and LTα +252 A/G+G/G genotypes (p<0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with −308G/A+A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR=3.9, p=0.0014, Pc=0.0098) and anti-Sm antibodies (OR=4.1, p=0.0002, Pc=0.0014). The present study suggests TNF-α −308A and LTα +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-α and LTα and concomitant discrete clinical features among Indian SLE patients.

Metabolic syndrome in patients with systemic lupus erythematosus from South India

ObjectivesTo find the prevalence of metabolic syndrome in systemic lupus erythematosus (SLE) compared to controls and to identify association of metabolic syndrome with SLE disease activity and damage. MethodsA total of 82 SLE and 82 healthy controls were studied. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), consensus definition for Asian Indian Adults and World Health Organisation (WHO) 1999 definition, and associations with lupus characteristics, disease activity, and damage were examined. Insulin resistance (IR) was estimated using the homeostasis model assessment for IR (HOMA-IR). ResultsMetabolic syndrome was present in 24.39% SLE and 12.19% controls (p<0.04) by NCEP ATP III criteria; 29.26% SLE and 19.51% controls (p=0.14) by consensus definition for Asian Indians; 18.2% SLE and 7.31% controls (p<0.035) by WHO 1999 criteria.Hypertension and hypertriglyceridemia were more frequent in SLE than in controls. Mean body mass index, diastolic and systolic blood pressure, triglycerides, and total cholesterol were higher in SLE than in controls. HOMA-IR (median, range) was 1.31 (0.06–9.32) and 1.55 (0.01–7.92), p=0.09 in SLE and controls, respectively. There was no association of metabolic syndrome with disease activity/damage and prednisolone use. SLE patients with metabolic syndrome had a significantly longer duration of disease compared to patients without metabolic syndrome. ConclusionSouth Indian SLE patients have higher prevalence of NCEP ATP III and WHO defined metabolic syndrome compared to healthy controls. SLE patients have an altered lipid profile, but there was no IR and no association of metabolic syndrome with disease activity or damage.

Association between PDCD1 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus in Three Main Ethnic Groups of the Malaysian Population.

The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants.

Prevalence and risk factors of a vascular necrosis in South Indian systemic lupus erythematosus patients

Prevalence and risk factors of a vascular necrosis in South Indian systemic lupus erythematosus patients

Vitamin D levels in Indian systemic lupus erythematosus patients: association with disease activity index and interferon alpha

IntroductionLow levels of vitamin D have been associated with several autoimmune disorders including multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus (SLE). The major source of vitamin D is sunlight but exposure of SLE patients to UV rays has been shown to exacerbate disease pathology. Studies in various populations have shown an association between low vitamin D levels and higher SLE disease activity.MethodsWe enrolled 129 patients who fulfilled American College of Rheumatology criteria in the study. There were 79 treatment-naïve cases and 50 patients who were under treatment for underlying SLE. There were 100 healthy subjects from similar geographical areas included as controls. Plasma 25-OH vitamin D3 and interferon (IFN)-α levels were quantified by enzyme-linked immunosorbent assay (ELISA). The gene expression level of IFN-α was determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR).ResultsPlasma 25-OH vitamin D3 significantly correlated in an inverse manner with systemic lupus erythematosus disease activity index (SLEDAI) scores (P <0.0001, r = -0.42), anti-dsDNA (P <0.0001, r = -0.39), plasma IFN-α (P <0.0001, r = -0.43) and levels of IFN-α gene expression (P = 0.0009, r = -0.45). Further, plasma levels of IFN-α positively correlated with gene expression of IFN-α (P <0.0001, r = 0.84). Treatment-naïve SLE patients displayed significantly higher plasma levels of IFN-α compared to patients under treatment (P <0.001) and controls (P <0.001).ConclusionsThese results suggest an important role of vitamin D in regulating disease activity in SLE patients and the need to supplement vitamin D in their treatment.

Effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in Indian SLE patients.

Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (P < 0.001). Mean level of IL-6 for patients with active disease (70.45±68.32 pg/mL) was significantly higher (P = 0.0430) than those of inactive disease patients (43.85±63.36 pg/mL). Mean level of TNF-α was 44.76±68.32 pg/mL for patients with active disease while it was 25.97±22.03 pg/mL for those with inactive disease and this difference was statistically significant (P = 0.0161). Similar results were obtained for IL-1β (P = 0.0002). Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (r = 0.20, r = 0.27, and r = 0.38, resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease.

Q222R polymorphism in DNAse I gene is a risk factor for nephritis in South Indian SLE patients

Systemic lupus erythematosus (SLE) is a multisystem disorder in which defective apoptotic clearance is considered to be an important factor in pathogenesis. DNAse I is associated with disposal of apoptotic nuclear debris. The defective enzyme production due to +2373 A to G (Q222R) in exon 8 is reported to be a genetic risk factor for SLE. SLE in Indians is reported to be severe. There are no genetic studies reported from India which have explored this aspect of DNAseI gene. This study aimed to analyze whether Q222R is a susceptibility factor for SLE and to study its influence on clinical manifestations and autoantibody production in South Indian Tamils. Three hundred SLE cases (based on ACR 1982 criteria) and 530 age, sex similar and ethnicity matched controls were recruited. All the cases and controls were genotyped for DNAse I Q222R polymorphism using PCR-RFLP method. DNAse I Q222R polymorphism is prevalent in our population. We observed higher frequency of Q/R in patients compared with controls (60% vs. 53%). This was found to be a genetic risk for SLE susceptibility (p = 0.04, odds ratio 1.5, 95% confidence interval 1-2.1). It also conferred a significant risk for development of nephritis (p = 0.007, odds ratio 1.93, 95% confidence interval 1.2-3.2). DNAse I Q222R polymorphism is a potential genetic risk factor for SLE in South Indian Tamils. In addition, the mutant allele confers a significant risk for lupus nephritis.

260 : Association of polymorphic variation of MCP-1 (-2518 A/G) SNP with clinical symptoms in systemic lupus erythematosus patients from western India

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder that affects multiple organs. The exact etiology of the disease is not clearly understood. Various polymorphisms in genes of inflammatory mediators influence development of the disease. In this study, we have tried to see the association of Monocyte Chemoattractant Protein-1 (MCP-1) −2518 A/G Single Nucleotide Polymorphism (SNP) with clinical symptoms in Indian SLE cohort. The case control study conducted on 173 clinically diagnosed Indian SLE patients and 163 ethnically matched healthy controls. The disease severity was categorised into mild, moderate and severe based on SLEDAI score. The SLEDAI score varied from 3 to 41. Genotyping of MCP-1 (−2518 A/G) polymorphism was performed using a (PCR-RFLP) method. Arthritis and Malar rash were the clinical manifestations predominantly seen among our SLE patients. We did not report a statistically significant difference (p > 0.05) in the distribution of MCP-1 −2518 A/G polymorphic variants among SLE patients (29.77%) as compared to healthy individuals (36.8%). When we tried to evaluate its effect on clinical manifestations, we found statistically significant association of MCP-1 (−2518A/G) polymorphisms with the renal disorder (p