Correlation between serum concentrations of soluble Fas (CD95/Apo-1) and IL-18 in patients with systemic lupus erythematosus.

Recent researches suggest that imbalance in apoptotic process may lead to susceptibility to systemic lupus erythematosus (SLE). Production of pro-inflammatory cytokines, such as IL-18, has important role in autoimmune process in lupus. There are cumulative data on the pro-apoptotic role of IL-18, in the Fas-mediated apoptosis. Soluble Fas (Apo/1-CD95) is a marker of apoptosis that appears to increase in serum of SLE patients. Previous studies demonstrated increasing serum concentrations of soluble Fas (sFas) and IL-18 in SLE. To assess the correlation between serum concentrations of sFas and IL-18 in SLE patients, 114 SLE patients were selected randomly at the different stages of disease activity according to SLEDAI2K. IL-18 and sFas serum concentrations were compared in patients and fifty randomly selected healthy volunteers. The correlations of IL-18 and sFas serum concentrations with SLEDAI2K and with each other were evaluated in patients. There were a significant difference between serum concentrations of sFas and IL-18 in the case and control groups (P = 0.001). There was a significant correlation between serum concentrations of sFAS and IL-18 in SLE patients (P < 0.0001, r = 0.411). The elevations of IL-18 and sFas(Apo/1-CD95) serum concentrations in SLE patients are significantly correlated.

Lack of association of vitamin D receptor gene BsmI polymorphisms in patients with systemic lupus erythematosus.

Several data link vitamin D to many autoimmune diseases. Association between vitamin D receptor (VDR) gene BsmI polymorphisms and systemic lupus erythematosus has been reported. In this study, we examine whether the VDR gene BsmI polymorphisms are markers for susceptibility to or severity of SLE. This study incorporated 60 patients with SLE living in northeastern Iran. Three genotypes, BB, Bb and bb, were detected based on polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP). The distribution of VDR genotyping in patients with SLE was 23.3% for BB, 60% for Bb and 16.7% for bb and in the control group was 33.3% for BB, 46.7% for Bb and 20% for bb (P = 0.334). No association of VDR gene BsmI polymorphisms with SLE disease activity index (SLEDAI), SLE damage score and major organ involvement was detected. The result of this study did not show any association between VDR gene BsmI polymorphisms and SLE.

T lymphocyte apoptosis in systemic lupus erythematosus patients.

OBJECTIVE(S): Apoptosis is a tightly regulated process and plays a crucial role in autoimmune diseases. Because abnormalities in apoptosis are considered to be involved in the pathogenesis of systemic lupus erythematosus (SLE), in present study we studied the apoptosis in T lymphocytes from Iranian SLE patients at protein and gene expression levels for some molecules which are involved in apoptosis pathways. MATERIALS AND METHODS: Thirty five SLE patients (23 female, 12 male), and 20 age matched controls (10 female, 10 male) participated in this study. T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) using MACS method. Apoptosis rate was studied at protein level by flow cytometer using Annexin V, and at gene expression level using semi-quantitative RT-PCR method for detection of Fas, FasL, Bcl-2, caspase 8, and caspase 9 genes. RESULTS: The percentage of apoptotic cells in SLE patients was not different in comparison with controls (20.2% ± 1.4 vs 21.1% ± 1.0), but the expression levels of FasL, caspase 8, and caspase 9 genes in all SLE patients and in female patients were significantly lower than controls; 0.45R vs 0.78R for FasL, 0.74R vs 1.0R for caspase 8, and 0.76R vs 1.26R for caspase 9 in all SLE patients and 0.37R vs 0.82R for FasL, 0.45R vs 1.6R for caspase 8, and 0.63R vs 1.56R for caspase 9 in female patients. CONCLUSION: The expression levels of FasL, caspase 8 and caspase 9 molecules involved in apoptosis decreased in female, but not in male SLE patients.

Is there any Association Between Human Lymphotropic Virus Type I (HTLV-I) Infection and Systemic Lupus Erythematosus? An Original Research and Literature Review.

OBJECTIVE(S): Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology. Some environmental factors can induce SLE in genetically susceptible individuals; for example, sun exposure and some viral infections may emerge the disease manifestations. Human T lymphotropic virus type 1 (HTLV-I) can dysregulate the human immune system, and the role of this virus in the pathogenesis of autoimmune diseases is under investigation. There are conflicting data about the role of HTLV-I in the pathogenesis of several autoimmune diseases such as SLE. In this study, we have focused on the correlation between HTLV-I infection and SLE in the northeast of Iran, an endemic area for the virus. MATERIALS AND METHODS: One hundred and thirty women with SLE and 915 healthy controls were screened for HTLV-I by enzyme linked immunosorbent assay (ELISA). Western blot method was used for confirmation of the positive results done by ELISA in the patients and the control group. RESULTS: Two (1.5%) of the patients and 23 (2.5%) of the healthy controls were HTLV-I seropositive. There was not a statistical difference between patients and controls in the number of HTLV-I seropositive samples (P=0.49). CONCLUSION: This cross-sectional case-control study did not find any association between HTLV-I and SLE. With regard to the previous studies, these controversies may stem from differences in ethnic background. Geographical and environmental factors should also be taken into account.

Association of urinary lipocalin-2 with lupus nephritis.

OBJECTIVE(S): Lupus nephritis (LN) is the main cause of mortality and disability in systemic lupus erythematosus (SLE) patients. Therefore, utilizing a reliable and non-invasive method for serial measurements of renal function seems to be necessary. The aim of this study was to evaluate the role of urinary lipocalin-2 as a biomarker of renal involvement in SLE patients. MATERIALS AND METHODS: Fifty two lupus patients in this cross sectional study were divided into two groups: patients with and without nephritis. For each group, urinary lipocalin-2, values were measured and reported according to urinary lipocalin-2/creatinine. Urinary lipocalin-2/creatinine sensitivity and specificity for identifying biopsy-proven nephritis were calculated, and a receiver operating characteristic (ROC) curve was constructed. Results : The mean urinary lipocalin-2/creatinine value of patients with biopsy-proven LN was 2.99 ± 4.1 ng/mg, and in non-LN patients was 1.16 ± 1.27 ng/mg. Urinary lipocalin-2/creatinine levels in LN patients were significantly higher than those in non-LN patients (P- Value = 0.03). In LN patients, urinary lipocalin-2/creatinine significantly correlated with proteinuria (r = 0.68; P = 0.0001). Using a cutoff value of 0.896 ng/mg, urinary lipocalin-2/creatinine had a sensitivity of 89.7% and a specificity of 39.1% for identifying SLE patients with biopsy-proven LN. The area under the ROC curve was 0.664 ± 0.076 with a 95% confidence interval of 0.52-0.81 (P=0.04). Analysis of variance showed that urinary lipocalin-2/creatinine is the same in different classes of LN (P-value=0.28). CONCLUSION: An important clinical conclusion is that measurement of urinary Lipocalin-2 may result in earlier diagnosis of LN.