Stages Of Systemic Lupus Erythematosus Research Articles

Patient Perspectives on a Decision Aid for Systemic Lupus Erythematosus: Insights and Future Considerations.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide spectrum of clinical manifestations. A decision aid (DA) for SLE was developed and implemented in 15 rheumatology clinics throughout the United States. This study explored the experiences of patients who viewed the DA to understand how patients engage with and respond to the SLE DA. We conducted a qualitative descriptive study using semistructured interviews with a convenience sample of 24 patients during May to July 2022. Patients recognized the value of the SLE DA in providing general knowledge about SLE and different treatment options. However, patients expressed a desire for more comprehensive lifestyle information to better manage their condition. Another theme was the importance of having multiple formats available to cater to their different needs, as well as tailoring the DA to different stages of SLE. This study contributes to a broader understanding of how to provide patient-centered care for patients with SLE by offering practical insights that can inform the development of more effective, patient-centric health information technologies for managing chronic diseases, ultimately improving patient outcomes. Overall, this study underscores the significance of optimizing both the information content and determining the appropriate delivery of the tool for its future sustainability.

Modelling the Impact of NETosis During the Initial Stage of Systemic Lupus Erythematosus

The development of autoimmune diseases often takes years before clinical symptoms become detectable. We propose a mathematical model for the immune response during the initial stage of Systemic Lupus Erythematosus which models the process of aberrant apoptosis and activation of macrophages and neutrophils. NETosis is a type of cell death characterised by the release of neutrophil extracellular traps, or NETs, containing material from the neutrophil’s nucleus, in response to a pathogenic stimulus. This process is hypothesised to contribute to the development of autoimmunogenicity in SLE. The aim of this work is to study how NETosis contributes to the establishment of persistent autoantigen production by analysing the steady states and the asymptotic dynamics of the model by numerical experiment.

Alterations and predictive value of blood routine parameters in patients with lupus enteritis: A retrospective study

Background Lupus enteritis (LE) is prone to incorrect and missed diagnoses. LE primarily occurs during the active stage of systemic lupus erythematosus (SLE), which often manifests with alterations in peripheral blood cell that may serve as indicators of disease activity and organ damage. This study aims to investigate the alterations and predictive value of routine blood parameters for LE diagnosis. Methods This exploratory study retrospectively analyzed the medical records of 36 patients with SLE who were admitted to Suining Central Hospital between January 2006 and April 2023. Additionally, a control group consisting of 72 SLE patients without LE, matched for sex and age, was enrolled. A comparison was made between the two groups regarding clinical characteristics and changes in routine blood parameters. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to identify independent risk factors and evaluate their diagnostic performance for LE. Results The LE group exhibited significantly higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), along with a lower lymphocyte count (LYM), compared to the control group ( p < .05). Binary logistic regression analysis revealed that NLR independently predicted the onset of LE, with an odds ratio of 1.347 and a 95% confidence interval of 1.070–1.696 ( p < .01). ROC curve analysis demonstrated that NLR had an area under the curve of 0.68 for diagnosing LE ( p < .05). When the cutoff value was set at 2.44, the Youden Index was only 0.31. Conclusion Significant differences were observed in several routine parameters between patients with LE and the control group, which can be attributed to the occurrence of LE during the active stage of SLE. However, only the NLR emerged as an independent risk factor for LE,and its predicting vulue for was insufficient; no blood routine parameter has been identified as an reliable predictor for LE.

Clinical profile of ocular morbidities associated with systemic lupus erythematosus

: Systemic lupus erythematosus (SLE) is an autoimmune disorder involving multiple organs. Ocular involvement occurs in both the active and chronic phases. We have conducted a study to illustrate the ocular inflammations associated with SLE leading to visual morbidity. : This prospective, descriptive, hospital-based study was conducted on 75 patients with SLE over 1 year diagnosed by the physician based on the Systemic Lupus Collaborating Clinics (SLICC) criteria. These patients underwent complete ocular examination. Ancillary investigations were done for patients with clinically suspected ocular pathology.: 69% patients had ocular involvement and keratoconjunctivitis sicca (76%) was the most common.42% patients had multiple ocular tissue pathologies. Corneal involvement was noted in 7 patients (14%), comprising of punctate corneal erosions (10%), pannus (2%) and peripheral corneal ulcer (2%), all during the active phase of the disease. 30% patients had episcleritis, diffuse pattern (73%) being the most common and also the presenting sign of SLE in 9% of patients. Retinopathy was seen in 9 patients (18%), vasculitis in 12% being the most common posterior segment association with SLE. The most common cause of defective vision in these patients was steroid induced or complicated cataract (24%). 42% of patients had associated SLE nephropathy.: Simultaneous and multiple forms of ocular inflammation can occur at any stage of SLE, which could compromise the quality of life of the individual. The onset of uveitis is indicative of active status of the disease. A complete ophthalmic evaluation is an important part of management during the active stage and remission.

A biological and a mathematical model of SLE treated by mesenchymal stem cells covering all the stages of the disease

In this study, we proposed a biological model explaining the progress of autoimmune activation along different stages of systemic lupus erythematosus (SLE). For any upcoming stage of SLE, any new component is introduced, when it is added to the model. Particularly, the interaction of mesenchymal stem cells, with the components of the model, is specified in a way that both the inflammatory and anti-inflammatory functions of these cells would be covered. The biological model is then recapitulated to a model with less complexity that explains the main features of the problem. Later, a 7th-order mathematical model for SLE is proposed, based on this simplified model. Finally, the range of validity of the proposed mathematical model was assessed. For this purpose, we simulated the model and analyzed the simulation results in case of some known behaviors of the disease, such as tolerance breach, the appearance of systemic inflammation, development of clinical signs, and occurrence of flares and improvements. The model was able to reproduce these events, qualitatively.

Acute Phase Reactants: Relevance in Dermatology.

Acute phase reactants (APRs) are a heterogeneous group of plasma proteins whose concentration either increases or decreases by at least 25% during an inflammatory process. The conditions that commonly lead to acute phase response are infection, trauma, burns, tissue infarction, inflammatory conditions, and advanced malignancy. APRs are elevated in all infective conditions. In skin and soft tissue infection, the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) help to predict the severity of infection. Procalcitonin can be used to differentiate between viral and bacterial infections. During active stages of systemic lupus erythematosus (SLE), ESR is elevated, but CRP either remains normal or shows only moderate elevation. In the case of superadded bacterial infection in SLE, CRP is elevated. In SLE, ferritin levels are elevated during the active stage of the disease. Serum amyloid antigen (SAA) and CRP levels are significantly higher in patients with early and late stages of diffuse systemic sclerosis. Elevated levels of serum ferritin are seen in rheumatoid arthritis and adult-onset Still's disease. CRP, SAA, and α2-macroglobulin (α 2M) are elevated in active psoriasis. In severe psoriasis, the ferritin-iron ratio is elevated. In drug-induced maculopapular rash, drug-induced hyperaemic vasculitis, and severe drug-induced cutaneous adverse reactions, CRP levels are elevated during the active stages. Neoplastic diseases in general are accompanied by increased serum ferritin. Further detailed studies are required to explore the clinical significance of APRs in dermatology and the scope of their possible application as a diagnostic tool.

Lipidomics Revealed Aberrant Lipid Metabolism Caused by Inflammation in Cardiac Tissue in the Early Stage of Systemic Lupus Erythematosus in a Murine Model.

Cardiac involvement, displayed as premature cardiovascular disease (CVD), is one of common clinical symptoms of patients with systemic lupus erythematosus (SLE), contributing to mortality of the disease. The precise underlying pathological mechanism(s) for the cardiac involvement in lupus remains poorly understood. Lipids and their metabolites are directly involved in atherosclerosis development, oxidative stress, and inflammation, which are closely related to the development of CVD. In the study, shotgun lipidomics was exploited to quantitatively analyze cellular lipidomes in the cardiac tissue of MRL/lpr mice at two different time points (i.e., pre-lupus and lupus state) with/without treatment with glucocorticoids (GCs). Urine protein, spleen index, and renal histopathological evaluation of the mice were also performed for assessment of SLE onset and/or outcome. Lipidomics analysis revealed that the deposition of cholesterol and the aberrant metabolism of lipids caused by the increased energy metabolism and the enhanced activation of phospholipases, both of which were originally induced by inflammation, were already present in cardiac tissues from lupus-prone mice even at pre-lupus state. These lipid alterations could further induce inflammation and autoimmune responses, accelerating the process of CVD. In addition, the present study also demonstrated that GCs therapy could not only delay the progression of SLE, but also partially corrected these alterations of lipid species in cardiac tissue due to their anti-inflammatory effect. Thus, the medications with better anti-inflammatory effect might be a useful therapeutic method for premature CVD of SLE.

Identification of novel classes for patients with lupus nephritis using two-step cluster model.

To identify and reclassify the patients in the lupus nephritis (LN) cohort, and to further analyze the prominent clinical features and clinical significance of each cluster. In this retrospective cross-sectional study, we used atwo-step clustering method to classify 635 patients with LN into different clusters, then we observed the main differences and analyzed relevant clinical significance between the clusters. Cluster1 (20.5%) presented with the highest disease severity, patients in this group had the disease for alonger duration and higher systemic lupus erythematosus disease activity index (SLEDAI) score, with multiple positive auto-antibodies and lower complement level. Patients of cluster2 (20.8%) had lower levels of IgG, IgA and IgM, with renal function being relatively worse in this cluster than in clusters1 and3. Cluster3 was the largest group (58.7%), and the patients in this group showed mild disease severity. This study reclassified LN patients in alarge cohort into three clusters. Our classification might be helpful to implement targeted therapy at various stages of systemic lupus erythematosus.

Forecasting index of unfavorable outcomes of systemic lupus erythematosus

The development of irreversible organ damage (IOD) in systemic lupus erythematosus (SLE) significantly increases the risk of death, worsens the quality of life and significantly increases the cost of treatment. The development and implementation of specific tools that will promote early identification of the risk of unfavorable outcomes is a priority. The article presents literature review on a new method for prediction of unfavorable outcomes in SLE – frailty index (FI, vulnerability index). FI, developed by a group of international experts on the basis of the database of the international cohort of SLE patients – SLICC (Systemic Lupus International Collaborating Clinics) – is easily reproducible in real clinical practice and can be used in patients with an early stage of SLE to predict the risk of death, the development of IOD. and hospitalization. The SLE Forecasting index of unfavorable outcomes (SLICC-FI) appears to be a promising clinical and research tool for identifying those who need more careful monitoring and an individual therapeutic strategy at an early stage of the disease.

Pregnancy outcomes in different stages of systemic lupus erythematosus among Chinese women - a retrospective cohort study.

To analyze the outcomes of pregnancies and risk factors in Chinese women with different stages of systemic lupus erythematosus (SLE). A total of 55 conceptions in 52 patients with SLE between Jan 2007 and Jan 2019 were retrospected systematically from a general hospital graded 3A in China. Medical records provided us a good way to retrieve the clinical parameters and lab data of patients. Pregnant women with SLE activity had significant hyperimmunoglobulin, hypocomplement, low platelet counts, high erythrocyte sedimentation rate, C-reactive protein and 24-h urine protein. Hydroxychloroquine had been used to reduce the rates of SLE activity in pregnant women. Logistic regression analysis showed low platelet counts, hypocomplement and 24-h urine protein were significantly correlated with fetal loss. Compared to those in stable stage, the active SLE patients have more risks of hypertensive disorders of pregnancy, thrombocytopenia, lupus nephritis and placental infarction, and have worse fetal outcomes, including the higher rate of fetal loss, preterm and asphyxia neonatorum. Different stages of SLE during pregnancy are closely related to maternal and fetal outcomes. It is imperative to provide SLE women with pregnancy consultation and regular multispecialty care.

Time Course of Metabolic Alterations Associated with the Progression of Systemic Lupus Erythematosus in MRL/lpr Mice Based on GC/MS.

Exploring the dynamic changes of metabolites and metabolic pathways during the development of the disease can help to further understand the etiology and pathogenesis of systemic lupus erythematosus (SLE). In this study, serum metabolomics based on gas chromatography/mass spectrometry (GC/MS) was employed to investigate the metabolic alterations at different stages of SLE using lupus-prone mice (MRL/lpr) of 9, 11, and 13 weeks of age. Multivariate statistical analysis was performed to view the alterations of metabolic profiles between MRL/lpr mice and age-matched C57BL/6 mice, and t-test and fold change criteria were used to identify differential metabolites at each stage. 11 changed metabolites were found in MRL/lpr mice at 9 weeks of age, which were mainly involved in the tricarboxylic acid (TCA) cycle, glycolysis, and butanoate metabolism; with the increase of week age, the TCA cycle was still disturbed, and the biosynthesis of fatty acids was significantly upregulated since 11 weeks of age; in addition, urea, urate, and indole-3-lactate were increased at 13 weeks of age. We found a time course of metabolic alterations in MRL/lpr mice, which may be related to the progression of SLE. These findings could provide a reference for studying the mechanism of SLE and judging the pathological stage and severity of the disease. The MS data have been deposited in Mendeley (https://www.mendeley.com/).

Systemic lupus erythematosus-associated diffuse alveolar hemorrhage: a single-center, matched case-control study in China.

This study described clinical characteristics and outcome in systemic lupus erythematosus (SLE) patients with diffuse alveolar hemorrhage (DAH), and investigated risk factors and prognostic factors for DAH. We conducted a retrospective nested case-control analysis in a single-center cohort. We enrolled 94 SLE patients with DAH. For each case of DAH, two age-, sex-, and SLE courses-matched controls were randomly selected from our cohort. All patients were enrolled between 2004 and 2019 and were followed until death, end of registration with the physician's practice, or end of January 2019. We estimated the risk factors for DAH and prognostic factors for mortality using multivariate analysis. We included 4744 patients diagnosed with SLE, with 94 cases of DAH, for an incidence rate of 2.0%. DAH may occur in any stage of SLE but mostly in the early phase of disease course. Lupus nephritis (LN) was the most common concomitant involvement at DAH diagnosis. By multivariate analysis, LN, anti-SSA positivity, thrombocytopenia and elevated C-reactive protein (CRP) were significantly associated with DAH in SLE patients. All-cause mortality was increased in SLE with DAH compared with SLE without DAH (adjusted hazard ratio 6.0, 95% confidence interval 2.8-13.0, p < 0.0001). Intravenous cyclophosphamide (CTX) showed an increased tendency for better survival in DAH after adjusting for Systemic Lupus Erythematosus Disease Activity Index 2000, acute kidney injury and mechanical ventilation. LN, anti-SSA positivity, thrombocytopenia and elevated CRP were independent risk factors of DAH in lupus patients. Due to a high early death rate of DAH and little long-term damage, DAH patients may benefit from early diagnosis and intensive treatment, and CTX-based therapy can be a preferential choice.

Identification of alterations in macrophage activation associated with disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by abnormalities in B cell and T cell function, but the role of disturbances in the activation status of macrophages (Mϕ) has not been well described in human patients. To address this, gene expression profiles from isolated lymphoid and myeloid populations were analyzed to identify differentially expressed (DE) genes between healthy controls and patients with either inactive or active SLE. While hundreds of DE genes were identified in B and T cells of active SLE patients, there were no DE genes found in B or T cells from patients with inactive SLE compared to healthy controls. In contrast, large numbers of DE genes were found in myeloid cells (MC) from both active and inactive SLE patients. Among the DE genes were several known to play roles in Mϕ activation and polarization, including the M1 genes STAT1 and SOCS3 and the M2 genes STAT3, STAT6, and CD163. M1-associated genes were far more frequent in data sets from active versus inactive SLE patients. To characterize the relationship between Mϕ activation and disease activity in greater detail, weighted gene co-expression network analysis (WGCNA) was used to identify modules of genes associated with clinical activity in SLE patients. Among these were disease activity-correlated modules containing activation signatures of predominantly M1-associated genes. No disease activity-correlated modules were enriched in M2-associated genes. Pathway and upstream regulator analysis of DE genes from both active and inactive SLE MC were cross-referenced with high-scoring hits from the drug discovery Library of Integrated Network-based Cellular Signatures (LINCS) to identify new strategies to treat both stages of SLE. A machine learning approach employing MC gene modules and a generalized linear model was able to predict the disease activity status in unrelated gene expression data sets. In summary, altered MC gene expression is characteristic of both active and inactive SLE. However, disease activity is associated with an alteration in the activation of MC, with a bias toward the M1 proinflammatory phenotype. These data suggest that while hyperactivity of B cells and T cells is associated with active SLE, MC potentially direct flare-ups and remission by altering their activation status toward the M1 state.

Failure to achieve lupus low disease activity state (LLDAS) six months after diagnosis is associated with early damage accrual in Caucasian patients\xa0with systemic lupus erythematosus

BackgroundThe aim was to assess the attainability and outcome of the lupus low disease activity state (LLDAS) in the early stages of systemic lupus erythematosus (SLE).MethodsLLDAS prevalence was evaluated at 6 (T1) and 18 (T2) months after diagnosis and treatment initiation (T0) in a monocentric cohort of 107 (median disease duration 9.7 months) prospectively followed Caucasian patients with SLE. Reasons for failure to achieve LLDAS were also investigated. Multivariate models were built to identify factors associated with lack of LLDAS achievement and to investigate the relationship between LLDAS and Systemic Lupus International Collaboration Clinics (SLICC)/Damage Index (SDI) accrual.ResultsThere were 47 (43.9%) patients in LLDAS at T1 and 48 (44.9%) at T2. The most frequent unmet LLDAS criterion was prednisolone dose >7.5 mg/day (83% of patients with no LLDAS at T1). Disease manifestations with the lowest remission rate during follow up were increased anti-double-stranded DNA (persistently present in 85.7% and 67.5% of cases at T1 and T2, respectively), low serum complement fractions (73.2% and 66.3%) and renal abnormalities (46.4% and 28.6%). Renal involvement at T0 was significantly associated with failure to achieve LLDAS both at T1 (OR 7.8, 95% CI 1.4–43.4; p = 0.019) and T2 (OR 3.9, 95% CI 1.4–10.6; p = 0.008). Presence of any organ damage (SDI ≥1) at T2 was significantly associated with lack of LLDAS at T1 (OR 5.0, 95% CI 1.5–16.6; p = 0.009) and older age at diagnosis (OR 1.05 per year, 95% CI 1.01–1.09; p = 0.020).ConclusionLLDAS is a promising treatment target in the early stages of SLE, being attainable and negatively associated with damage accrual, but it fit poorly to patients with renal involvement.

Sera of Human Beings Hosting Durably Viscerotropic Leishmania Species Display Histones- Binding Immunoglobulins: A Feature To Consider When Probing Signatures of Auto-Reactivity?

When being asked to extract molecular immune signatures, at the preclinical stage of Systemic Lupus Erythematosus (SLE), the analysts who received the subjects’ blood monitor the presence and titers of autoantibodies against a more or less extended panel of SLE associated autoantigens. Tunisian subjects are known to stably share habitats where zoo anthropophilic blood-feeding sand flies and Leishmania infantum co-perpetuate. We were curious to add three other antigenic sources depicted below. Two serum biobanks were selected in the original publication. Analysis from the second shown, four sera containing high titers of mammalian histones autoantibodies as well as a range of ENA-binding autoantibodies. Combined tests that allow detecting antibodies signing risks of developing SLE as well as exposure to viscerotropic Leishmania species, whenever physicians addressed blood of healthy subjects inhabiting areas where perpetuate these species L. chagasi/infantum and L. donovani. L. donovani is the second species within the genus Leishmania to share these so-called viscerotropic features with L. chagasi/ infantum. We were not in the position to disentangle the genetic and environmental components that could account for the multiple positive serologic tests in healthy subjects. It will be important to broaden the spectrum of differential diagnoses in healthy subjects at risk of developing auto immune diseases when they stably inhabit areas where sand flies and viscerotropic Leishmania species coperpetuate.

Multiple dermatofibromas in a patient with systemic lupus erythematosus and Sjögren’s syndrome

We report a case of multiple dermatofibromas in a patient with systemic lupus erythematosus (SLE) and Sjögren's syndrome. He was treated with prednisolone, diaphenylsulfone, and cyclosporine for SLE. He noticed two brown nodules on his right lower leg 3 years after the first consultation. Subsequently, six nodules developed within 6 months, and 2 more nodules after 10 months. Histopathological examination of a nodule on his left hand showed fibrotic proliferation with a storiform pattern in the whole dermis, but neither necrosis nor mitosis was observed. From these findings, a diagnosis of multiple dermatofibromas was made. As these tumors appeared during the remission stage of SLE, they might have been under immunosuppressive conditions caused by immunosuppressing agents rather than collagen disease itself.

Pregnant outcomes and prognosis of women complicated with systemic lupus erythematosus

Objective To understand the clinical features, management, pregnant outcomes and prognosis of pregnant women complicated with systemic lupus erythematosus (SLE). Methods Retrospective analysis of 34 women (35 pregnancies) complicated with SLE were conducted and 26 of them were followed up for 0.5～15 years. Results (1) Out of the 35 pregnancies in these 34 women, 8 were in remission stage, 8 in the well-controlled period, 1 in active phase and 18 were primary onset (10 diagnosed during the pregnancy, and 8 after terminations) during the pregnancy. (2) Among those diagnosed during the pregnancy, 2 women in the remission group and 3 in the well-controlled group were in the active stage of SLE. The several most common clinical manifestations indicating SLE deterioration were proteinuria, fatigue, edema, hypertension, erythra and decreased serum C3. (3) In women with onset during the pregnancy, 7 (38.9%) presented with proteinuria, edema and hypertension which similar to symptoms of gestational hypertension. (4) The average maternal age of the remission group was much older than those women with onset during pregnancy [(32.4±5.5) years vs (26.6±3.9) years, P=0.034]. while the proportion of active lupus nephritis was lower than that of the later (1/4 vs 16/16, P=0.004) and the well-controlled group (1/4 vs 6/6,P=0.033) during post-partum follow-ups. Conclusions Pregnancy prompted lupus nephritis has nothing to do with maternal age, but the stage of SLE. Patients who conceived in the remission stage are the least likely to have nephritic damage. Although women with onset during the pregnancy is relatively young, they are expected to have more serious renal damage and poor prognosis. Key words: Pregnancy complications; Lupus erythematosus, systemic; Lupus nephritis; Pregnancy outcome

Type I Interferons Inhibition of Inflammatory T Helper Cell Responses in Systemic Lupus Erythematosus

T helper (Th) cells play a central role in systemic lupus erythematosus (SLE). Activated autoreactive Th cells provide the help required for autoreactive B cells to differentiate and produce pathogenic autoAbs. Both autoAb-containing immune complexes and direct effects of inflammatory Th cells promote tissue injury and organ damage. In SLE, triggering of plasmacytoid dendritic cell (pDC) Toll-like receptors by autoimmune complexes containing nucleic acid autoantigens stimulates pDC secretion of high levels of type I interferons (IFN-alpha/beta). Study of SLE patients and murine disease models implicate these type I IFNs as key disease effectors. However, the role of pDC-derived type I IFNs in regulating the inflammatory function of Th cells in SLE is unknown. Although, type I IFNs are classically considered to promote Th1-mediated inflammation, they can also act as potent inhibitors of both Th1 and Th17 inflammatory cell responses. Work of ourselves and others leads us to hypothesize that if initiated during stages of SLE when Th cell-mediated tissue inflammation is absent or minimal, such as early in the disease or during periods of remission, type I IFN neutralization will disrupt the cycle of systemic autoimmune induction and disease. However, if initiated during advanced stages of disease when there is substantial ongoing Th1 (and possibly Th17) cell-mediated inflammation, targeting type I IFNs will exacerbate the Th cell-mediated inflammatory disease and thus potentiate end-organ damage and destruction. This has important implications for the application of the numerous anti-type I IFN therapies currently under development for SLE treatment.

全身性エリテマトーデスにおけるリンパ球のテロメラーゼ活性およびテロメア長の異常

T-cell telomerase activity was high in the active and inactive stages of systemic lupus erythematosus (SLE). In contrast, B-cell telomerase activity was very high only in the active stage. Compared with normal subjects, SLE patients had a shorter T-cell telomere, but their B-cell telomere length did not differ from that of normal subjects. These findings suggest that T cells are always activated, and that the manifestation of the disease requires the activation of not only T but also B cells. B-cell inhibition alone may be sufficient to suppress the clinical symptoms of SLE, but we consider that the essential treatment of SLE should target T cells as well. In recent years, various biologicals have begun to be used for the treatment of SLE. It is interesting how the use of such biologicals in the future will change T- and B-cell telomerase activity. In formulating a therapeutic strategy using biologicals for SLE, the measurement of telomerase activity in T and B cells seems useful for the preparation of target cells, selection of therapeutic drugs, and evaluation of therapeutic responses.

Prevalence of anti-3-nitrotyrosine antibodies in the joint synovial fluid of patients with rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus

Background Increased reactive nitrogen species (RNS) production has been suggested in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis (OA) as well as in systemic lupus erythematosus (SLE). They are known to have direct toxicity to cells. High concentrations of serum nitrite/nitrate and elevated urinary nitrate : creatine ratio has been found in patients with RA, OA and SLE. Reactive nitrogen species play a role in the chronicity of inflammatory reaction such as cartilage and bone destruction seen in patients with RA and OA. Arthritis is also associated with increased intra-articular formation of 3-nitrotyrosine (3-NT), which may contribute to joint damage. There is growing evidence that nitrative injury plays an important role in oxidative stress in the etiology and pathogenesis of SLE. 3-nitrotyrosine is thought to be a relatively specific marker of nitrosative damage mediated by nitric oxide (NO) and its by-products. Methods Commercially available poly l-tyrosine was exposed to nitrating species resulting in the formation of 3-nitrotyrosine. Antibodies present in synovial fluid and sera of 30 patients with rheumatoid arthritis, 15 patients with osteoarthritis and 15 patients with SLE were studied for their recognition of 3-NT by direct binding ELISA. Results IgG from the synovial fluid (SF) of RA and OA patients, purified on protein A-Sepharose matrix, exhibited increased recognition of 3-NT, than the IgG isolated from the sera of RA and OA patients in competitive ELISA, whereas IgG isolated from the sera of SLE patients exhibited increased recognition of 3-NT, than the IgG isolated from the synovial fluid. There was a higher prevalence of antibodies against 3-NT in the synovial fluid than in the sera of patients with RA and OA. Higher level of anti-3-NT antibodies were found in the synovial fluid in the later stages of SLE when compared to the early stages but was not more than that found in the sera. Conclusion The RNS may be produced within the inflamed joints of RA and OA patients but not in SLE patients. The 3-NT levels also correlated directly with disease activity.