Group Of Systemic Lupus Erythematosus Patients Research Articles

Study of Serum Complement 3 Split Product iC3b /C3 Ratio in a Cohort of Systemic Lupus Erythematosus Patients

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that causes widespread multi organ inflammation. The exact cause of SLE remains unclear; however, genetic, hormonal, and environmental factors contribute to the development of the disease. Aim of the Work The aim of this study is to measure the ratio of complement split product iC3b to C3 and its relation to disease activity and lupus nephritis in a cohort of SLE patients. Patients and Methods This study is a Cross sectional case control study conducted in internal medicine and Rheumatology unit, Ain Shams university hospital and Rheumatology unit, Maadi military hospital. Our study included. Results The present study shows that female were (76%) in active group of SLE patients and (60%) in inactive group while male were (24%) and (40%) respectively. with no significant difference. The mean of Disease Duration was (5.66 ± 1.97) with a range from 3 and 10 years in active group of SLE patients and (5.08 ± 1.54) with a range from 3 and 9 years in inactive group. with no significant difference. Regarding clinical manifestations of SLE the present study shows that active group of SLE patients had statistically highly significant increase in incidence of lupus nephritis, arthritis, serositis, oral ulcers, malar rash (p < 0.001) with significant increase in incidence of alopecia and neurological manifestations (p < 0.05). The current study shows that active group of SLE patients had statistically significantly higher mean ESR, anti-DNA titre, 24hr urinary proteins, serum creatinine, serum urea, and GFR levels (p = 0.000) than inactive group, Also active group had significant leucopenia, anemia (p = 0.000, 0.005 respectively) and C3 was significantly more consumed than inactive group (p < 0.05) Conclusion The ratio of complement split product iC3b to C3 concentrations correlates with the extent of SLE disease activity more than C3 alone. Furthermore, the iC3b:C3 ratio may discriminate between patients with lupus nephritis and patients without lupus nephritis. Detection of SLE disease activity and lupus nephritis by iC3b/C3 ratio help to make a proper decision in management to induce remission.

The Dynamic Role of PD-1, Vitamin D, RANKL, and Sclerostin in Iraqi Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease, with a wide range of clinical symptoms. Some studies have indicated the association between RANKL, Sclerostin, PD-1, and vitamin D concentrations and the pathogenesis of SLE. The current study aimed to evaluate the role of RANKL, Sclerostin, PD-1 and vitamin D in the pathogenesis of SLE. The study included 180 females diagnosed SLE patients and healthy control (60 females as early diagnosed patients without treatment, 60 females as patients under treatment with (prednisolone, and hydroxychloroquine), and 60 females healthy as a control group, with ages ranging from 20 to 45 years. The serum concentration levels of RANKL, Sclerostin, PD-1 and vitamin D were assessed by Enzyme linked immunosorbent assay (ELISA). The results of the current study showed no significant differences in the serum levels of RANKL and Sclerostin in both SLE patients’ groups (early diagnosed group and treated) compared with the control group (p<0.05). The serum level of PD-1 was significantly higher in both SLE patients’ groups compared with the control group (p<0.05). The serum level of vitamin D was significantly lower in both SLE patient groups compared with the control group (p<0.05). Based on these results, PD-1 may be considered a good therapeutic target for SLE and the level of vitamin D must be sufficient level especially in SLE patients.

Levels of VCAM-1 and ICAM-1 in serum of active and inactive Systemic Lupus Erythematosus patients as biochemical markers for risk of cardiovascular disease

Background: Cardiovascular complications represent one of the consequences of chronic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), which has significant rates of morbidity and mortality. Dyslipidemia can be brought on by steroid medications, which are frequently given to SLE patients and are considered to be one of the major risk factors for cardiovascular diseases. Objectives: This study attempted to investigate a potential association between circulating vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) as risk factors for atherosclerosis and their relationship to cardiovascular risk. Patients and methods: A total of 100 patients and 50 apparently healthy controls were included in the study. All patients were from the Department of Rheumatology, Baghdad Hospital / Medical City during the period from 1 December 2021 to 1 March 2022 who were all treated with antimalarial drugs as immunosuppressants such as chloroquine (CQ) or hydroxychloroquine HCQ). They were divided according to the SLE disease activity index 2000 (SLEDAI-2K) into the active group (SLEDAI ≥ 10) and the inactive group (SLEDAI). Results: Serum VCAM and ICAM were significantly high in all study groups of SLE patients. The VCAM mean ± SD were (271.9±63.90), (247.9±82.92) and (97.7±24.69) in the active, inactive controls respectively. The ICAM mean ± SD were (3.1±0.91), (2.7±0.79) and (1.8±0.22) in the active, inactive and controls respectively. The values have increased gradually with increasing disease activity. The area under curve (AUC) of ICAM and VCAM were (0.802), (0.776) in active SLE patients and (0.858), (0.674) in inactive SLE patients. However, the AUC of VCAM and ICAM in active group were the highest. Conclusion: In SLE patients, VCAM-1 and ICAM-1 serum levels may operate as disease detection and severity differentiation indicators, and they may be linked to the number of coronary lesions in people at risk of developing CVD. Received: Aug.,2022 Accepted: Sept., 2022 Published: April 2023

Markers of NETosis in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.

Neutrophil Extracellular Traps (NETs) have been implicated in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) pathogenesis. The myeloperoxidase-deoxyribonucleic acid (MPO-DNA) complex and nucleosomes are serum markers of NETosis. The aim of this study was to assess these NETosis parameters as markers for SLE and APS diagnosis and their association with clinical features and disease activity. A total of 138 people were included in the cross-sectional study: 30 with SLE without APS, 47 with SLE and APS, 41 patients with primary antiphospholipid syndrome (PAPS), and 20 seemingly healthy individuals. Serum MPO-DNA complex and nucleosome levels were determined via an enzyme-linked immunosorbent assay (ELISA). Informed consent was obtained from all subjects involved in the study. The Ethics Committee of the V.A. Nasonova Research Institute of Rheumatology (Protocol No. 25 dated 23 December 2021) approved the study. In patients with SLE without APS, the levels of the MPO-DNA complex were significantly higher compared to patients with SLE with APS, with PAPS, and healthy controls (p < 0.0001). Among patients with a reliable diagnosis of SLE, 30 had positive values of the MPO-DNA complex, of whom 18 had SLE without APS, and 12 had SLE with APS. Patients with SLE and positive MPO-DNA complex levels were significantly more likely to have high SLE activity (χ2 = 5.25, p = 0.037), lupus glomerulonephritis (χ2 = 6.82, p = 0.009), positive antibodies to dsDNA (χ2 = 4.82, p = 0.036), and hypocomplementemia (χ2 = 6.72, p = 0.01). Elevated MPO-DNA levels were observed in 22 patients with APS: 12 with SLE with APS and 10 with PAPS. There were no significant associations between positive levels of the MPO-DNA complex and clinical and laboratory manifestations of APS. The concentration of nucleosomes was significantly lower in the group of SLE patients (±APS) compared to controls and PAPS (p < 0.0001). In SLE patients, the frequency of low nucleosome levels was associated with high SLE activity (χ2 = 13.4, p < 0.0001), lupus nephritis (χ2 = 4.1, p = 0.043), and arthritis (χ2 = 3.89, p = 0.048). An increase in the specific marker of NETosis, the MPO-DNA complex, was found in the blood serum of SLE patients without APS. Elevated levels of the MPO-DNA complex can be regarded as a promising biomarker of lupus nephritis, disease activity, and immunological disorders in SLE patients. Lower levels of nucleosomes were significantly associated with SLE (±APS). Low nucleosome levels were more common in patients with high SLE activity, lupus nephritis, and arthritis.

Nailfold Video-Capillaroscopic Changes in Adult Bangladeshi Patients With Systemic Lupus Erythematosus: Correlation With Disease Activity

Background: Peripheral microangiopathy is an important feature in systemic lupus erythematosus (SLE). Nailfold capillary (NFC) changes observed by nailfold videocapillaroscopy (NVC) may play a role in early detection of microangiopathy and assessment of disease activity in SLE. The aim of the study was to evaluate nailfold capillary changes, their diagnostic accuracy and NFC-pattern of changes in a group of Bangladeshi SLE patients in comparison to healthy subjects and to determine the correlation with disease activity in SLE. Methods: This cross-sectional study with a comparison group was conducted in CMCH, Chattogram; a Tertiary Care Hospital in Bangladesh. Results: Twenty-seven (n=27) Bangladeshi SLE patients who were diagnosed by ACR-1997 revised criteria for diagnosis of SLE and Twenty-seven (n=27) age-sex matched health subjects were included. All participants were subjected to full history taking, clinical examination, laboratory investigations as well as NVC examination. SLE disease activity was assessed by SLEDIA scoring tool and nailfold capillary changes were assessed with NFC-pattern of changes by applying NVC. Results: Mean (±SD) age of the SLE patient group was 31.2 (±7.8) years and female to male ratio was around 6:1. 23 out of 27(85.2%) patients had multiple phenotypes and 18 (66.6%) had either high or very high disease activity. Sub-papillary venous plexus (SPVP) was prominently visible more frequently in SLE patients and capillary density was reduced in SLE patients compared with healthy controls. Capillary changes in NVC were observed in 26 out of 27 (96.3%) patients. Major and scleroderma pattern were detected in 51.9% and 11.1% of the SLE patients; respectively. Nailfold capillary abnormalities were significantly more frequent in SLE patient than in healthy controls. More frequently found different abnormal morphological changes were seen with crossed capillary (66.7%), tortuous capillary (63%) and meandering capillary (37%). There was a significant positive correlation between disease activity of SLE and NFC-pattern of changes (r=0.443, p=0.021). Conclusion: Different abnormal nailfold capillary changes are quite common among patients with SLE, and nailfold capillary changes positively correlate with disease activity in SLE. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 208

Correlation Between Gene Expression of Interferon Regulatory Factor-5 and Disease Activity Index in Systemic Lupus Erythematosus Iraqi Patients

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by elevated levels of circulating anti-nuclear autoantibodies and interferon-alpha (INFs-α). Interferon regulatory factor-5 (IRF5) plays an important role in the induction of type I interferon and pro-inflammatory cytokines, and participates in the SLE pathogenesis. This study aimed to investigate the role of IRF5 gene expression levels in a sample of SLE Iraqi patients and its correlation with disease activity, and to identify its diagnostic ability as a biomarker reflecting disease activity. Blood samples were taken from 45 participants diagnosed with SLE cases classified according to the American College of Rheumatology (ACR) criteria. They were scored via the SLE disease activity index 2000 (SLEDAI-2K) to assess the disease activity and according to it, they were subdivided into “SLE (I) group” (SLEDAI-2k ≤5), and “SLE (II) group” (SLEDAI-2k &gt;5), as well as age and gender matched healthy control group. RNA was isolated from whole blood samples and gene expression levels of IRF5 were determined using real-time polymerase chain reaction (PCR). Our results revealed that the expression levels of the IRF5 gene were significantly increased in SLE (I) and SLE (II) patient groups compared with the control group (p&lt;0.05, and p&lt;0.01) respectively, as well as higher in SLE (II) group than the SLE (I) group (p&lt;0.01). Moreover, the expression levels of IRF5 were found to be related positively and significantly to the disease activity index in both SLE patient groups. The analysis of receiver operator curves (ROC) for gene expression levels of IRF5 in SLE (II) group showed a perfect accuracy to distinguish between SLE patients and healthy individuals (AUC=0.989, sensitivity= 95.5%, and specificity= 88.0%). However, in SLE (I) group showed a good accuracy to discriminate between SLE patients and healthy individuals. (AUC=0.769, sensitivity= 69.6%, and specificity= 80.0%). The correlation between gene expression levels of IRF5 with other parameters revealed that a significant positive correlation was found with uric acid and ALP in SLE (I) group, while in SLE (II) group with urea, creatinine, and uric acid. Our conclusion suggests that the up-regulation of IRF5 gene expression levels correlates positively with disease activity in SLE patients reflecting the possibility of using it as an immunological biomarker for diagnosis, and monitoring the disease flare.

Short- and mid-term outcomes in systemic lupus erythematosus patients presenting with disease exacerbation after SARS-CoV-2 mRNA vaccination: A cohort study from Puerto Rico.

To determine if SARS-CoV-2 mRNA vaccination has an impact on the clinical course of systemic lupus erythematosus (SLE). Puerto Ricans with SLE who received mRNA COVID-19 vaccines were studied. Demographic parameters, clinical manifestations, disease activity (per Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), disease damage (per Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), emergency room visits, hospitalizations, and pharmacologic therapy were determined. Baseline variables (prior to vaccination) were compared between patients with and without exacerbation after SARS-CoV-2 vaccination. Among those with exacerbation, clinical outcomes were determined up to 1year after vaccination. Of the entire cohort (n = 247), 14 (5.7%) had post-vaccination exacerbations. Photosensitivity, oral ulcers, anti-Ro antibodies, higher SLEDAI score, and corticosteroids exposure were associated with post-vaccination flares. Among those with post-vaccination flares, 10 (71.4%) had major organ involvement. No significant differences were observed for mean SLEDAI scores, emergency room visits, hospitalizations, disease damage, and exposure to immunosuppressive drugs before and after SARS-CoV-2 mRNA vaccination. At 12months of follow-up, all patients were fully controlled without evidence of active disease. In our group of SLE patients, 5.7% had a disease flare after SARS-CoV-2 mRNA vaccination. Most had exacerbations involving major organs/systems. Mucocutaneous manifestations, anti-Ro antibodies, disease activity, and corticosteroids were associated with flares. Awareness of these factors and the possibility of a major lupus flare after vaccination with COVD-19 vaccines is critical to provide timely and effective therapy.

Povezanost dužine trajanja bolesti i primenjene terapije sa metaboličkim sindromom kod pacijenata obolelih od sistemskog eritemskog lupusa

Aim. The aim of the paper was to examine the impact of disease duration and administered therapy on the development of metabolic syndrome (MetS) in patients with systemic lupus erythematosus (SLE). Material and methods. This study involved 55 patients (50 females and 5 males) with the diagnosis and 49 healthy controls of similar age. MetS was defined according to modified NCEP-ATP III diagnostic criteria, and obesity was defined by body mass index BMI &gt; 30. Results. In the group of SLE patients with MetS, there were 23 individuals (41.82%). In the control group, there were 10 (20.4%) patients with MetS. There were significantly more SLE patients with MetS in comparison to the controls (p = 0.04). Duration of the disease in the group with MetS was longer in comparison to those without MetS, but it was not statistically significant (15.35 ± 10.26 vs 10.44 ± 7.88, p = 0.073). The study confirmed that there is a moderate association (CC = 0.355) between disease duration and number of MetS parameters, however, this dependency was not statistically significant (p = 0.439). In the group without MetS, there were statistically more patients treated with antimalarial drugs monotherapy (p = 0.023). It has been found that the patients with MetS were treated with corticosteroid therapy longer than those without MetS, but it was not statistically significant (153.57 ± 103.34 vs 114.75 ± 83.32, p = 0.129). Conclusion. Patients with longer SLE duration have more often MetS. It has been shown that, statistically, more patients without MetS were treated with antimalarial drugs monotherapy, and that long-term CS use, in our study, was not associated with higher incidence of MetS.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study.

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud's arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (-1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position -1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Circulating levels of Interferon regulatory Factor-5 correlates with disease activity in Systemic Lupus Erythematosus Iraqi patients

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a diversity of the phenotypes among the patients. SLE is still one of the great challenges due to the lacking of specific biomarkers for diagnosis, assessing disease activity, and prediction of response to therapy. This study aimed to investigate the role of circulating levels of IRF5 protein in sample of SLE Iraqi patients and its correlation with disease activity, to identify a potential immunological biomarker to mirror disease activity.&#x0D; Methods: Blood samples were taken from 59 participants diagnosed with SLE cases classified according to the American College of Rheumatology (ACR) criteria. They were scored through the SLE disease activity index 2000 (SLEDAI-2K) to estimate the disease activity, and according to it they were subdivided into “SLE-1 group” (SLEDAI-2k ≤5), and “SLE-2 group” (SLEDAI-2k &gt;5), as well as age and gender matched healthy control group. Circulating levels of IRF5 protein were measured in sera samples by ELISA method.&#x0D; Results: Our result revealed that the circulating levels of IRF5 protein were significantly higher in the SLE-2 group rather than control group (p&lt;0.01), while there was a non-significant difference between SLE-1 group and control group (p&gt;0.05), as well as between both SLE patient groups. Moreover, the circulating IRF5 protein levels were found to be correlated positively and significantly with disease activity index in both SLE patient groups. The correlation between the circulating levels of IRF5 protein with other parameters revealed that a significant positive correlation was found in SLE-1 group with ESR and globulins, and negative correlation with Hb and (albumin/ globulin) ratio, while in SLE-2 group were positively correlated with urea, creatinine, and uric acid. The analysis of receiver operator curves (ROC) for circulating levels of IRF5 protein in SLE-1 and SLE-2 groups showed a good accuracy to distinguish SLE patients from healthy individuals (AUC=0.758, sensitivity=65.5%, and specificity=69%,), and (AUC=0.788, sensitivity=77.3%, and specificity=72.0%,), respectively.&#x0D; Conclusions: The circulating levels of IRF5 protein correlate with disease activity in SLE patients reflects the possibility of using it as a potential immunological biomarker for diagnosis, and monitoring the disease activity.

Serum Cytokine Levels of Systemic Lupus Erythematosus Patients in the Presence of Concomitant Cardiovascular Diseases.

Systemic lupus erythematosus (SLE) is known to be associated with an increased risk of cardiovascular diseases (CVD). SLE patients suffer from CVD 3.5 times more often than healthy people. Cytokine-mediated inflammation is actively involved in the development of cardiovascular pathology. Here, we analyzed serum levels of nine cytokines of steroids-treated SLE patients depending on the presence of concomitant CVD. The levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, IL-21, tumor necrosis factor α (TNFα), B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) were analyzed using multiplex immunoassay. In the total group of SLE patients (n=29), the concentrations of IL-6 and IL-10 were higher, and the APRIL level decreased compared to healthy donors (n=39, p<0.05). The same changes were observed in the group of patients without CVD (n=15); the levels of IL-6 and IL- 10 were found to be increased, and the level of APRIL was lower than in healthy individuals (p<0.05). In the group of SLE patients with CVD (n=14), the concentrations of IL-4, IL-6, IL- 10, and TNFα were found to be increased (p<0.05). Interestingly, the levels of TNFα and BAFF in SLE patients with CVD were higher than in patients without cardiovascular pathology. Thus, TNFα and BAFF levels were significantly altered in SLE with concomitant CVD compared to SLE without CVD. These findings suggest that cytokine profiles in SLE with concomitant CVD and SLE without CVD are different, which should be considered in further research with large samples.

Depression-, Pain-, and Health-Related Quality of Life in Patients with Systemic Lupus Erythematosus.

Objectives A significant number of patients with systemic lupus erythematosus (SLE) have depression, and many are untreated. We aim to assess the frequency of moderate to severe depression (MSD) in a multiethnic group of SLE patients with different sociodemographic backgrounds, identify modifiable factors associated with depression, and determine the impact of depression, disease activity, damage, cognitive function, and pain severity on health-related quality of life (HRQoL). Methods Ninety-nine patients with SLE were evaluated in a cross-sectional study. Sociodemographic data, Beck Depression Inventory (BDI II), SLE disease activity index (SLEDAI-2K), SLICC Damage Index (SLICC-DI), pain severity (10 cm visual analogue scale), cognitive function (Automated Neuropsychologic Assessment Metrics (ANAM)), and the physical (PCS) and mental (MCS) component scores of the Short Form Health Survey (SF-36) were recorded. Bivariate analysis identified potential associations of relevant variables with BDI II and SF-36. Regression analysis determined independent correlates with MSD, PCS, and MCS. Results Over 50% of subjects (50.5%) were African-American, 37.1% had a family income of ≤$20,000, and 31.3% had MSD. In the bivariate analysis, family income, SLEDAI-2K, cognitive function, and pain severity were associated with MSD. Using binary logistic regression, SLEDAI-2K and pain severity remained independently correlated with MSD (p = 0.004). In the multiple linear regression analysis, pain severity was the only independent correlate of PCS (p < 0.0001), while cognitive function and BDI II were the main factors associated with MCS (p = 0.020 and p < 0.0001, respectively). Conclusion Pain severity and disease activity are associated with MSD in our unique population, are potentially modifiable, and deserve further attention in the clinic. Depression and pain significantly affect HRQoL and should be aggressively managed.

The dynamics of Th17 / Treg ratio in SLE patients during pregnancy

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder that affects women at childbearing age. During pregnancy, maternal immune system is challenged to tolerate a semi-allogenic fetus and a shift toward a tolerogenic profile is essential. Failure to develop this tolerogenic profile seems to be associated with the development of adverse obstetric outcomes. We conducted a prospective longitudinal observational study where peripheral blood lymphocyte subsets were analyzed during pregnancy in a group of SLE patients and compared with healthy gestations. We observed a reduction in peripheric Treg cell count throughout all pregnancy in control patients, which was not observed in SLE patients. In contrast, the Th17 cell count remained stable in both groups. In the control group, the Treg/Th17 ratio decreased throughout pregnancy to the postpartum, which was not observed in the study group. These changes may be justified by the migration of the immunotolerant Treg cells to the maternal decidua and may lead to the establishment of a pro-inflammatory profile by the end of pregnancy in healthy pregnancies, which was not observed in the SLE pregnant patients. This pro-inflammatory state at the end of a healthy pregnancy may be necessary for the spontaneous beginning of labor and help to explain why systemic syndromes like preeclampsia develop during the second half of pregnancy. The lack of these findings in SLE patients may express a pro-inflammatory state from the beginning of pregnancy, the influence of immunomodulatory medication or an intrinsic deregulation of immune function, which is a characteristic of these patients.

Study on the Relationship between lncRNA Gene Polymorphism and Systemic Lupus Erythematosus.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease that can cause damage to multiple systems of the body. A number of studies have shown that long-chain noncoding RNA (lncRNA) can participate in the occurrence and development of a variety of autoimmune diseases. This study is aimed at detecting the expression levels of 5 lncRNAs in SLE patients and healthy controls and at exploring the relationship between expression levels and clinical symptoms and laboratory indicators. Methods The design type of this study is a case-control study. A total of 76 SLE patients and 71 healthy controls were included in the first phase of the study. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression level of 5 kinds of lncRNAs including lnc7514, lnc0640, lncagf, nc3643, and lnc5150 in PBMCs of two groups of patients; the expression of lncRNAs in the case group and the control group was analyzed. We analyzed the differences in the expression levels of lncRNAs between case and control groups, and explored the association of expression levels with clinical manifestations and laboratory characteristics. SPSS23.0 was used to analyze the expression level and gene polymorphism results; the statistical analysis test level α = 0.05. Results The expression level of lnc0640 in PBMCs of SLE patient group was higher than that of healthy control group (Z = −3.56, P = 0.03). However, lnc5150 was lower than in healthy controls (Z = −7.16, P < 0.001). lnc3643 expression levels were lower in SLE patients of SLE patients with pleurisy was lower than that of patients without pleurisy (Z = −2.44, P = 0.02). Low lnc3643 expression levels were observed in PBMCs with SLE patients with rash symptoms (Z = −2.75, P = 0.013). SLE expressed lower lnc3643 levels in PBMCs with SLE compared with those without pleurisy (Z = −2.42, P = 0.02). The above differences were statistically significant. Association analysis of lncRNA expression levels and clinical manifestations in SLE patients found that SLE was lower than those without rash or pleurisy (both P < 0.05); association analysis of lncRNA expression level and laboratory results found a negative correlation between lnc3643, lnc7514, and SLE disease activity score (SLEDAI-2K), blood sink (ESR), and C-reactive protein (CRP) (all P < 0.05). Conclusions lnc0640 was overexpressed in PBMCs in SLE patients compared with healthy controls. lnc3643 was negatively correlated with SLEDAI, and expression levels were associated with SLE patients with arthritis, rash, and pleuritis.

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease

BackgroundAdult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology, lacking specific diagnosis and disease activity evaluation indicators. This study will analyze the activity and clinical significance of Adenosine deaminase (ADA) in AOSD patients.MethodsTotally 53 AOSD patients, 60 patients with other autoimmune diseases including systemic lupus erythematosus (SLE), sjogren syndrome (SS) and rheumatoid arthritis (RA), as well as 60 healthy subjects were included in this study. AOSD activity was determined by Pouchot score. We analyzed the correlation between ADA activity and clinical parameters. In addition, the correlation between ADA activity and disease activity score was also analyzed.ResultsThis study showed that the activity of ADA in AOSD patients was significantly higher than that of healthy controls, SLE, SS and RA patient groups (p < 0.0001). The ADA activity of AOSD patients decreased significantly after systemic treatment (p < 0.0001). Correlation analysis showed that ADA activity was positively correlated with ALT(r = 0.54, p < 0.0001), AST (r = 0.82, p < 0.0001) and serum ferritin (r = 0.67, p < 0.001). ADA activity was negatively correlated with white blood cell (r = − 0.42, p = 0.002) and platelet counts (r = − 0.44, p = 0.001). We also found a significant positive correlation between the activity of ADA and Pouchot score in AOSD patients (r = 0.51, p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that ADA activity had a sensitivity of 93.3%, and a specificity of 83% for the diagnosis of AOSD, with an area under the curve of 0.93.ConclusionThis study showed that serum ADA activity can be used as a potential biomarker for AOSD diagnosis and disease activity assessment.

Annexin A1 and its receptor gene polymorphisms in systemic lupus erythematosus in the Tunisian population.

An association between ANXA1, FPR1 and FPR2 gene polymorphisms and the patho-physiology of many human diseases was suggested by numerous studies. Our study aimed to evaluate association between common polymorphisms in the 9q21.13 and 19q13.41 and susceptibility to systemic lupus erythematosus (SLE) in the Tunisian population. We performed a case-control study on 107 Tunisian SLE patients and 122 healthy controls to explore 9 polymorphisms of the three studied genes: rs2811226 and rs3739959 (ANXA1), rs5030880, rs1042229, rs1461765570, rs17849971, rs867228 (FPR1), rs17694990 and rs11666254 (FPR2). Four polymorphisms were found to be linked with SLE susceptibility: rs3739959-ANXA1 > G and GG (p = 0.021, OR = 1.73 and p = 0.014, OR = 2.06 respectively), rs867228-FPR1 > TT (p = 0.014, OR = 4.59), rs11666254-FPR2 > GG (p = 0.019, OR = 8.34) and rs17694990-FPR2 > T (p = 0.05, OR = 1.506). In homogenous groups of SLE patients depending on clinical manifestations and serological results, previous associations were confirmed with a panoply of manifestations of lupus including lupus nephritis, malar rash, mouth ulceration and hypocomplementia. Our study showed an association between ANXA1 > rs3739959, FPR1 > rs867228, FPR2 > rs11666254, FPR2 > rs17694990 and SLE susceptibility. Our results also showed a strong association between the two ANXA1 studied SNPs and LN which allowed us to suggest these two SNPs as biomarkers of LN development in SLE. Further research is needed to understand by which mechanism the gene variants affect susceptibility to SLE. Key Points • Lupus erythematosus is an autoimmune disease in which a panoply of factors are implicated • Annexin A1 interaction with its receptors are suggested as a target in therapy of a panoply of human disease in particular cancers • The present results highlighted the implication of Annexin A1 and its receptors gene polymorphisms in the physiopathology of lupus, in particular in the involvement of renal and cutaneous lesions.

Fibroblast growth factor-23 in systemic lupus erythematosus patients: Is there a correlation with interleukin-6 and left ventricular mass?

Background: Chronic kidney disease (CKD) and left ventricular hypertrophy (LVH) are common features of systemic lupus erythematosus (SLE) patients. Fibroblast growth factor 23 (FGF23) is a phosphatonin that steadily increases in serum of CKD patients. High FGF23 is associated with inflammation, CKD progression, and LVH. Aim of the work: To determine any possible role of FGF23 in SLE patients and its relation with interleukin 6 (IL6) and LVH. Patients and methods: Two groups of SLE patients were studied: group I (n = 30) with eGFR > 90 ml/min/1.73 m2 and group II (n = 30) with eGFR <90−>15 ml/min/1.73 m2 as well as 60 controls. IL6, FGF23 and left ventricular mass index (LVMI) were assessed. Results: The mean age of the patients was 25.25 ± 10.65 years (14–55 years) and disease duration was 4.75 ± 5.66 years. Serum FGF23 in SLE patients was comparable to controls (99.6 ± 79.86 vs 139 ± 12.3 pg/mL, p > 0.05). There was no significant difference in serum levels of FGF23 or IL6 between the two SLE groups (106.49 ± 88.2 vs 93.84 ± 74.67 pg/mL, p = 0.56 and 58.6 ± 63.69 vs 55.9 ± 47.97 ng/L respectively, p = 0.85). LVMI was significantly higher in group II than in group I (187.6 ± 81.7 vs 138.6 ± 36.59 respectively, p = 0.0045). FGF23 showed a significant correlation with IL6 (r = 0.78, p < 0.001), but not with LVMI. Conclusion: FGF23 behaves differently in SLE patients; in spite of the significant increase in inflammation and the frequent renal involvement, FGF23 level remains normal in SLE patients raising a possibility of the existence of an FGF23 inhibitor in SLE patients.

Classification of systemic lupus erythematosus in children and adults

Systemic Lupus Erythematosus (SLE) is an autoimmune multisystem disease with a variable clinical phenotype and no single clinical, laboratory or pathological feature that can be used as a gold standard for disease classification or diagnosis. Classification criteria have been developed in an attempt to define homogenous groups of SLE patients for clinical research. They have been mainly validated in adult cohorts, given the much lower prevalence of SLE before puberty. The three commonly used sets of current classification criteria and their validation studies to date are described in this review. Challenges relating to classification of SLE patients, including important differences across age-groups and ethnicities, are explored along with future directions in the classification of SLE.

Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican.

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02∼C∗16:01∼B∗44:03∼DRB1∗07:01∼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.

Humoral Immunity to Varicella Zoster Virus in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis Compared to Healthy Controls.

Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases.