Expression Of Systemic Lupus Erythematosus Research Articles

Interferon-stimulated gene 15 expression in systemic lupus erythematosus : Diagnostic value and association with lymphocytopenia.

The aim of this study was to (a) assess the relationship between interferon-stimulated gene 15 (ISG15) expression and clinical manifestations of systemic lupus erythematosus (SLE) and (b) investigate the diagnostic value of ISG15 in SLE. The study comprised 28 patients newly diagnosed with SLE, 10 patients with undifferentiated connective tissue disease, and 22 healthy volunteers. Of the SLE patients, 14were chosen randomly to be followed up for 4weeks. ISG15 expression in whole blood cells was determined by quantitative polymerase chain reaction. Clinical and laboratory parameters were recorded at baseline and after treatment. The ISG15 mRNA level was higher in whole blood cell counts of SLE patients when compared with the disease control and healthy control groups. Moreover, it was correlated with SLE disease activity as assessed via the SLE disease activity index, serositis, and anemia at baseline. ISG15 expression correlated with lymphocytopenia in active SLE patients before treatment. On receiver operating characteristic curve analysis, the area under the curve for ISG15 expression was 0.826 (p= 0.000015). ISG15 expression is relatively high in SLE patients and correlates with disease activity before treatment. ISG15 expression is higher in SLE patients with lymphocytopenia before treatment.

Does parvovirus infection have a role in systemic lupus erythematosus?

We sought to evaluate a possible link between parvovirus B19 infection and the clinical and laboratory expression of systemic lupus erythematosus (SLE). SLE patients were examined to evaluate their clinical status and disease activity. A complete Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was obtained for each patient. In addition, we determined the level of systemic involvement throughout the course of the disease. Blood levels of IgM and IgG antibodies to parvovirus B19, levels of anti-dsDNA, C3, and C4 were measured. A PCR real-time assay was used to determine the presence of parvovirus B19 genetic material. The viral genome was found in sera of 2 of 51(3.9%) patients with SLE. There was no correlation between viral serology and the clinical and serological parameters of the disease. More SLE patients with secondary antiphospholipid syndrome (APS) had IgG and IgM antibodies to the virus (p<0.029 and p<0.018, respectively). These patients also had a higher titer of IgG antibodies to parvovirus B19 compared to SLE patients without APS. In this group of SLE patients, no association was found between parvovirus infection and the presence or activity of SLE. The results of the study suggest an association between parvovirus infection and antibody production directed against phospholipids.

Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis.

Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p < 0.002). A higher incidence of microhaemorrhages was seen in patients with active SLE disease ( p < 0.04). In SLE patients with active skin involvement, the disturbed distribution ( p < 0.004) was more frequent and subtle changes ( p < 0.009) were less frequently observed as compared with patients without active skin involvement. In the group of SLE patients with renal involvement, no correlation was found between the capillary abnormalities and the presence of renal involvement ( p > 0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

Reduced sB7-H3 Expression in the Peripheral Blood of Systemic Lupus Erythematosus Patients.

Both membrane-bound and soluble forms of costimulatory molecules play important roles in immune-regulatory networks. B7-H3, a member of the B7 family, has been found with aberrant expression in tumors and infectious disease. However, the significance of sB7-H3 expression in systemic lupus erythematosus (SLE) has not been investigated. Using the peripheral blood of 78 SLE patients, we established a comprehensive database containing clinical data and relevant laboratory tests. We found that sB7-H3 expression in SLE patients was significantly lower compared with the healthy individuals. In addition, sB7-H3 levels in the patients were positively correlated with the disease activity as indicated by SLE disease activity index score, rashes, fever, and inflammatory cytokines. Moreover, sB7-H3 was associated with the counts of red blood cells and hemoglobin. Our findings suggest that sB7-H3 might counteract the aberrant immune response and potentially serve as a monitoring indicator of disease progression and therapeutic target in SLE treatment.

Blood-Borne RNA Correlates with Disease Activity and IFN-Stimulated Gene Expression in Systemic Lupus Erythematosus.

The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.

A study of the influence of ethnicity on serology and clinical features in lupus.

The objective of this study was to review the links between ethnicity, serology and clinical expression in systemic lupus erythematosus (SLE) in a single cohort that was followed over a 36-year period. Patients with SLE treated at the University College London Hospitals (UCLHs) between January 1978 and December 2013 formed the cohort. We assessed the demographic, clinical and serological data. Standard methods were used for laboratory testing. The Student t test and Mann-Whitney U test were used for the continuous variables; the Fisher's exact test was used for the categorical variables. We studied 624 SLE patients: There were 571 women (91.5%), with a mean age at diagnosis of 29.0 ± 6.5 years; and 53 men (8.5%), with a mean age at diagnosis of 29.4 ± 15.3 years. Ethnically, 369 of the patients were European, 100 were Afro-Caribbean, 77 were East Asian, 56 were South Asian and 21 were of mixed ethnicity. The East Asian patients developed the disease at a younger age than the other ethnic groups (p < 0.0001). The Afro-Caribbean patients were less frequently associated with the presence of rash and photosensitivity, and the non-European patients were more likely to have alopecia and renal involvement. The South Asian patients were significantly associated with musculoskeletal and neurological involvement, serositis, Sicca syndrome and hematological features. The Afro-Caribbean patients had the highest prevalence of anti-Smith, anti-RNP, anti-Ro and anti-La antibodies. Anti-IgG anticardiolipin (aCL) antibodies were significantly associated with the non-East Asian groups; and hypocomplementemia was common in the East Asians. Rash, alopecia, mouth ulcers, serositis, neurological, joint and renal involvement were significantly associated with the presence of anti-Smith and anti-RNP antibodies in the Afro-Caribbean group. We also observed an association of joint involvement and the presence of anti-Ro and anti-La antibodies in this group. The East Asian patients developed their SLE disease at a younger age than the other ethnic groups. Cutaneous involvement was more frequent in those who were not Afro-Caribbean. Serositis, joint and neurological involvement were more frequently diagnosed in the South Asian patients. Anti-ENA antibodies were frequently associated with the Afro-Caribbean patients.

Effects of 1,25-dihydroxyvitamin D3 on IL-17/IL-23 axis, IFN-γ and IL-4 expression in systemic lupus erythematosus induced mice model.

Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL-23, IL-4 and IFN-γ were assessed in activated chromatin-induced mouse model for SLE. Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3 starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-γ were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits. The results showed that IL-17, IL-23, and IFN-γ mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL-23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer. Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE.

Aberrant regulation of gene expression in systemic lupus erythematosus

Aberrant regulation of gene expression in systemic lupus erythematosus

A novel role of peptidyl-prolyl isomerase-1 as inducer of IL-6 expression in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations affecting different tissues. Pro-inflammatory cytokines, such as interleukin 1β, IL-6 and IFN-g are associated with the SLE progression; however, the precise molecular mechanisms that in occurs improper cytokines production in SLE remain unknown. Autoantibody production and renal disease were evaluated in NZB/W F1 mice treated with a specific Pin1 inhibitor, Juglone. Inhibition of Pin1 activity significantly suppressed the IL-6 expression in NZB/W F1 mice and developed milder renal lesions than the lesions developing in non Juglone-treated mice. We further found that Pin1 inhibitor treatment suppresses B-cell differentiation and T-cell activation in NZB/W F1 lupus mice. Finally, stat3 phosphorylation was decreased in T cells from Pin1inhibitor-treated mice at 40 weeks of age as compared to that from the saline and isotype control mAb treatment groups. This is the first study to demonstrate that Pin1 plays critical roles in SLE development. Pin1 inhibition to the appropriate level might provide a novel therapeutic strategy target for future SLE therapies.

A novel role of peptidyl-prolyl isomerase-1 as inducer of IL-6 expression in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations affecting different tissues. Pro-inflammatory cytokines, such as interleukin 1β, IL-6 and IFN-g are associated with the SLE progression; however, the precise molecular mechanisms that in occurs improper cytokines production in SLE remain unknown. Autoantibody production and renal disease were evaluated in NZB/W F1 mice treated with a specific Pin1 inhibitor, Juglone. Inhibition of Pin1 activity significantly suppressed the IL-6 expression in NZB/W F1 mice and developed milder renal lesions than the lesions developing in non Juglone-treated mice. We further found that Pin1 inhibitor treatment suppresses B-cell differentiation and T-cell activation in NZB/W F1 lupus mice. Finally, stat3 phosphorylation was decreased in T cells from Pin1inhibitor-treated mice at 40 weeks of age as compared to that from the saline and isotype control mAb treatment groups. This is the first study to demonstrate that Pin1 plays critical roles in SLE development. Pin1 inhibition to the appropriate level might provide a novel therapeutic strategy target for future SLE therapies.

Interferon regulatory factor 1 marks activated genes and can induce target gene expression in systemic lupus erythematosus.

Interferon regulatory factor 1 (IRF-1) mediates both induction of interferons (IFNs) and responses to type I IFNs. It has been implicated as a critical mediator of inflammation in murine lupus models. In a previous study of chromatin modifications in monocytes from patients with systemic lupus erythematosus (SLE), IRF-1 was implicated as being associated with increased histone acetylation in this disease. The present study was undertaken to directly investigate IRF-1 binding sites on chromatin. Cells from 9 female SLE patients and 7 female controls were examined. Monocytes were purified from peripheral blood and subjected to library preparation using a validated antibody to IRF-1. IRF-1 binding sites on chromatin were identified by chromatin immunoprecipitation followed by sequencing. The effect of IRF-1 on target gene expression was confirmed using an overexpression system in cell lines, and coimmunoprecipitation was used to identify protein interactions. IRF-1 binding around transcribed regions was increased in SLE patient monocytes, but histone modifications at potential IRF-1 binding sites without detectable IRF-1 binding were increased as well. Overexpression of IRF-1 was sufficient to drive transcription of target genes. IRF-1 overexpression was also able to alter histone modifications at a focus set of target genes, and treatment with an IRF-1 inhibitor reduced both expression and histone modifications at target genes. IRF-1 was found to interact with a select set of histone-modifying enzymes and other transcription factors. IRF-1 is an important signaling protein in the interferon pathway. It not only activates gene expression as a transcription factor, but may perpetuate disease by leading to a dysregulated epigenome.

Hematological abnormalities and autoantibodies expression in systemic lupus erythematosus: A monocentric cohort of South Indian tamils

Hematological abnormalities and autoantibodies expression in systemic lupus erythematosus: A monocentric cohort of South Indian tamils

Clinical and immunological pattern of systemic lupus erythematosus in men in a cohort of 2355 patients

To investigate the impact of gender on expression of systemic lupus erythematosus (SLE) in a cohort of 2355 SLE patients as one of the largest series of cases among the present reports. In this retrospective study we used medical records of all patients (239 male and 2116 female) of the SLE registry of Rheumatology Research Center (RRC), Tehran University of Medical science (TUMS), Iran. Both clinical and paraclinical manifestations of SLE patients have been registered in this database since 1976 and updated during their follow-up. Chi-square test was used to compare the clinical and paraclinical manifestations in men and women at disease onset and during the disease course. We used logistic regression to compute odds ratios with 95% confidence intervals. A P-value < 0.05 was considered as statistically significant. Mean age at disease onset was 25 ± 11.8 and 24.5 ± 10.3 years in men and women, respectively (P = 0.48). Comparison of clinical and immunological manifestations showed that male patients had a higher prevalence of mucocutaneous (43.5% vs. 33.7%, P = 0.005) and a lower prevalence of musculoskeletal symptoms (44% vs. 54.7%, P = 0.003) as the initial manifestation. During the disease course, discoid rash (25.9% vs. 13%, P = 0.000) and type IV lupus nephritis (23.4% vs. 18.1%, P = 0.03) were significantly more common, whereas arthritis (61.1% vs. 71.7%, P = 0.01) and leukopenia (28.5% vs. 35.8%, P = 0.024) were significantly less common in men. This study reveals gender influence on some manifestations of SLE. Considering sex differences is recommended in diagnostic and therapeutic features of the disease.

Increased expression of Mer tyrosine kinase in circulating dendritic cells and monocytes of lupus patients: correlations with plasma interferon activity and steroid therapy

IntroductionThe requirement for the immunoregulatory Mer tyrosine kinase (Mer) for optimal removal of apoptotic cells prompted us to look at its expression in systemic lupus erythematosus (SLE), in which apoptotic cell clearance is abnormal. We compared the levels of expression of Mer in normal human subjects and in patients with SLE.MethodsWe used flow cytometry of isolated peripheral blood mononuclear cells to compare the levels of Mer on leukocyte subsets. We used a Mer-specific enzyme-linked immunosorbent assay (ELISA) to quantify soluble Mer (sMer) in plasmas.ResultsMonocytes, CD1c+ myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from both normal individuals and from SLE patients expressed Mer. In both normal and SLE patients, the CD14++CD16+ subpopulation of monocytes expressed the highest levels of Mer, with somewhat lower levels on the CD14intCD16+ population. Mer levels on CD1c+ mDCs and pDCs, and sMer levels in blood were increased in SLE patients compared with controls. In patients, Mer levels on CD14intCD16+, CD14++CD16- monocytes, and CD1c+ dendritic cells correlated positively with type I interferon (IFN-I) activity detected in blood. In SLE patients treated with corticosteroids, Mer expression on monocytes correlated with prednisone dose, CD1c+ myeloid dendritic cells in patients treated with prednisone had higher levels of Mer expression than those in patients not receiving prednisone.ConclusionsWe found no global defect in Mer expression in lupus blood. In contrast, we observed increased levels of Mer expression in DC populations, which could represent a response to increased IFN-I in SLE patients. Enhanced Mer expression induced by corticosteroids may contribute to its beneficial effects in SLE.

CASPASE-12 genotype influences the expression of systemic lupus erythematosus in African-Americans (P4090)

Abstract CASPASE-12 (CASP12) modulates inflammation by down-regulating inflammatory cytokines. CASP12 is a risk factor for sepsis in persons of African ancestry, as the functional CASP12 allele is present in about 20% of persons of African descent. Nearly all other human populations lack a functional CASP12 gene. Systemic lupus erythematosus (SLE) is a serious and complex autoimmune disease affecting multiple organ systems and is most common in African-American (AA) women. To determine if CASP12 may be protective against SLE, 596 AA SLE patients and 296 healthy controls from the Lupus Family Registry and Repository were genotyped for CASP12. Serum from 30 patients and controls was assayed by antibody arrays for 23 inflammatory cytokines and chemokines. There was a significant association between CASP12 and protection against serositis. CASP12 homozygosity was seen only in controls, and CASP12 was only in female, but not male patients without serositis compared to those with serositis. In male patients, CASP12 was protective against the development of arthritis. Expression of the Mig chemokine was statistically different between patients and controls, independent of genotype. No influence of CASP12 genotype was seen upon serum cytokine levels in patients vs controls. The results indicate that CASP12 is protective against lupus serositis and arthritis in AA patients, with possible gender influences for both. In addition, chemokines may contribute to the pathogenesis of SLE.

Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations

American Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients. A total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). The average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement. In general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.

Toll-like receptor 9 in systemic lupus erythematosus, impact on glucocorticoid treatment

Aim: To assess TLR9 expression in systemic lupus erythematosus (SLE) patients, its correlation with disease activity, and impact of TLR9 expression on the response to oral glucocorticoids. Methods: Twenty-five active SLE, 15 inactive, and 15 control subjects were included. Anti-DNA, ANA, C3, C4, and TLR9 mRNA expressions were assessed. Active SLE patients only received oral steroid for 6 weeks. Post therapy, they were classified into steroid sensitive and steroid resistant. Data were reassessed after treatment. Results: SLEDAI, anti-DNA, ANA, and TLR9 expressions were significantly higher in active SLE patients. Based on retrograde analysis, TLR9 expression was significantly higher in steroid-resistant versus steroid-sensitive group before treatment, with no significant difference between them after treatment. There was a significant positive correlation between TLR9 expression and SLEDAI score and anti-DNA and negative correlation with C3 and C4 in all patients. Conclusion: TLR9 may play a role in the pathogenesis of SLE and correlates with the disease activity. Corticosteroids have no effect on TLR9 expression, explaining lack of corticosteroid response in some SLE patients. TLR 9 expression can be used in predicting glucocorticoid response in active SLE patients. New treatment modalities targeting TLR9 expression may be of value in steroid-resistant patients.

Enhanced interferon regulatory factor 3 binding to the interleukin‐23p19 promoter correlates with enhanced interleukin‐23 expression in systemic lupus erythematosus

To examine the role of interferon regulatory factor 3 (IRF-3) in the regulation of interleukin-23 (IL-23) production in patients with systemic lupus erythematosus (SLE). Bone marrow-derived macrophages were isolated from both wild-type and IRF3(-/-) C57BL/6 mice. These cells were stimulated with the Toll-like receptor 3 (TLR-3) agonist poly(I-C), and IL-23p19 cytokine levels were analyzed by enzyme-linked immunosorbent assay. IRF-3 binding to the IL-23p19 gene promoter region in monocytes from patients with SLE and healthy control subjects was analyzed by chromatin immunoprecipitation (ChIP) assay. Luciferase reporter gene assays were performed to identify key drivers of IL-23p19 promoter activity. TANK-binding kinase 1 (TBK-1) protein levels were determined by Western blotting. ChIP assays demonstrated that IRF-3 was stably bound to the human IL-23p19 promoter in monocytes; this association increased following TLR-3 stimulation. Patients with SLE demonstrated increased levels of IRF-3 bound to the IL-23p19 promoter compared with control subjects, which correlated with enhanced IL-23p19 production in monocytes from patients with SLE. Investigations of the TLR-3-driven responses in monocytes from patients with SLE revealed that TBK-1, which is critical for regulating IRF-3 activity, was hyperactivated in both resting and TLR-3-stimulated cells. Our results demonstrate for the first time that patients with SLE display enhanced IL-23p19 expression as a result of hyperactivation of TBK-1, resulting in increased binding of IRF-3 to the promoter. These findings provide novel insights into the molecular pathogenesis of SLE and the potential role for TLR-3 in driving this response.

Mannose-binding lectin gene polymorphisms in Brazilian patients with systemic lupus erythematosus

The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematosus susceptibility, but studies in Brazilian population have not been conducted. To examine potential associations of mannose-binding lectin alleles G57E, G54D, IVSnt5, R52C and R52H with susceptibility to and clinical expression of systemic lupus erythematosus in southern Brazilian patients, we conducted a case-control study with 327 consecutive patients with diagnosis of systemic lupus erythematosus and 345 healthy controls. Genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction assay. A statistically significant difference in the frequencies of allele R52C was observed in European-derived systemic lupus erythematosus patients when compared with controls (9.6% vs. 3.3%, p < 0.001, odds ratio: 3.15, 95% confidence interval: 1.76-5.62, p < 0.05). The frequencies of alleles G54D and G57E were not different between European-derived systemic lupus erythematosus patients and controls. There were no differences between clinical and laboratory features in systemic lupus erythematosus patients according to the presence or absence of mannose-binding lectin allelic variants. These results support an increased risk of systemic lupus erythematosus in European-derived individuals carrying allele R52C. Patients carrying this allele have an approximately three-fold higher odds ratio of developing systemic lupus erythematosus when compared with controls. Our data do not support associations between the mannose-binding lectin allelic variants studied and clinical expression of systemic lupus erythematosus.

Shared and Unique Gene Expression in Systemic Lupus Erythematosus Depending on Disease Activity

Patients presenting with active systemic lupus erythematosus (SLE) manifestations may exhibit distinct pathogenetic features in relation to inactive SLE. Also, cDNA microarrays may potentially discriminate the gene expression profile of a disease or disease variant. Therefore, we evaluated the expression profile of 4500 genes in peripheral blood lymphocytes (PBL) of SLE patients. We studied 11 patients with SLE (seven with active SLE and four with inactive SLE) and eight healthy controls. Total RNA was isolated from PBL, reverse transcribed into cDNA, and postlabeled with Cy3 fluorochrome. These probes were then hybridized to a glass slide cDNA microarray containing 4500 human IMAGE cDNA target sequences. An equimolar amount of total RNA from human cell lines served as reference. The microarray images were quantified, normalized, and analyzed using the R environment (ANOVA, significant analysis of microarrays, and cluster-tree view algorithms). Disease activity was assessed by the SLE disease activity index. Compared to the healthy controls, 104 genes in active SLE patients (80 repressed and 24 induced) and 52 genes in nonactive SLE patients (31 induced and 21 repressed) were differentially expressed. The modulation of 12 genes, either induced or repressed, was found in both disease variants; however, each disease variant had differential expression of different genes. Taken together, these results indicate that the two lupus variants studied have common and unique differentially expressed genes. Although the biological significance of the differentially expressed genes discussed above has not been completely understood, they may serve as a platform to further explore the molecular basis of immune deregulation in SLE.