21Sanatorio Parque, Rosario, Argentina PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z ¼ 2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N ¼ 149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N ¼ 90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
Pulmonary complications of primary antiphospholipid syndrome are common and diverse, with thromboembolic events counting as the most frequent manifestation. We present the case of a female patient with a diagnosis of primary antiphospholipid syndrome, pulmonary thromboembolism and infarction followed by lung cavitation.
Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.
Background Lupus nephritis (LN) is one of the most severe forms of Systemic Lupus Erythematosus (SLE). Given that the kidney is the main site of inflammation in LN, biomarkers in urine may reflect this inflammation more closely than those in the blood. Many groups have studied messenger RNA (mRNA) expression of urinary biomarkers in patients with SLE, investigating which is likely to be most helpful for monitoring renal disease activity. Endostatin (END) is a natural proteolytic fragment of collagen XVIII and has been known to have modulatory function in angiogenesis and inflammation. In contrast to the general angiogenic factors, the expression profiles and activity of angiogenic inhibitors like END in LN are not well defined. Objectives We proposed to study gene expression level of END in urine from LN patients. Methods A total of 45 patients, 36 with renal involvement and 9 non-renal were included. Urine samples from active patients were divided according Protein Creatinin ratio (P/C) as: Group 1, P/C <1 (n=18) and Group II, P/C>1 (n=18), and non renal patients: Group III (n=9). Levels of gene expression of END were measured using Quantitative Real Time PCR (QPCR). All amplifications were carried out in duplicate and threshold cycle (Ct) scores were averaged for calculations of relative expression values. The Ct scores were normalized by subtracting the corresponding β2Microglobuline (β2M) control, or ΔCt=Ct,gene − Ct,B2M. To test for differential gene expression between groups a variance analysis (ANOVA) and t test was performed. Results ΔCt is inversely proportional to the gene expression level. Urinary END was significantly decreased in active renal SLE patients compared with no-renal SLE patients (Table 1). Among active renal patients, END gene expression was elevated in Group I compared with Group II (test t, p=0.0192). Table 1. Levels of END gene expression between groups (ANOVA, p=0.0327) END (mean ΔCt) SLE patients p=0.0327 Active renal No-renal Group I (P/C <1) Group II (P/C >1) Group III 6,521 9,572 5,414 Conclusions Urinary END had the capacity to discriminate patients with active renal SLE from those with no-renal disease and exhibited the lowest urinary level in patients with P/C >1. This study provides evidence that measuring urinary END could be an important new biomarker in patients with SLE without renal activity. References Angiogenesis and hypoxia in the kidney. Tanaka T et al. Nat. Rev. Nephrol. 9, 211-222 (2013). Can measuring urinary biomarkers improve the management of Lupus Nephritis? Rahman A. Arthritis Research & Theraphy. 14, 127 (2012). Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5600
BackgroundLupus nephritis (LN) is a severe complication of Systemic Lupus Erythematosus (SLE). Non-invasive biomarkers are needed for diagnosis of LN and to identify patients at risk of a renal flare (1). Thus the presence of biomarkers associated with inflammation, tissue damage or cell activation in the urine of patients with LN may be a useful tool in the evaluation of LN patients.The glomerular filtration rate (GFR) is considered the best overall index of renal function in health and disease. Because GFR is difficult to measure in clinical practice, most clinicians estimate the GFR (eGFR) from the serum creatinine concentration (2).B Lymphocyte Stimulator (BLyS) is a cytokine that fosters B cell activation, antibody production, B cell - T cell interaction and plasma cell survival. These events have been demonstrated to play a role in patients with LN (3).ObjectivesWe evaluated urinary levels of BLyS as biomarker for LN and their relationship with eGFR.MethodsUrine samples (n=86) were obtained from LN patients and classified in two groups: patients with eGFR >60 (GFRhigh, n=68, 62F/6M, age: 34.07±13.24) and patients with eGFR ≤60 (GFRlow, n=18, 14F/4M, age: 35.22±13.76). RNA from urine samples was isolated using TRIzol-Chloroform technique and then reverse-transcribed using random primers. Levels of BLyS expression were evaluated using Quantitative Real Time PCR (QPCR). All amplifications were carried out in duplicate and threshold cycle (Ct) scores were averaged for calculations of relative expression values. The Ct scores were normalized against Ct scores by subtracting the corresponding β2Microglobuline (β2M) control, or DCt=Ct,gene- Ct,B2M.To test for differential gene expression between groups, a two sample t-test was performed to compare the DCt in the two groups.ResultsDCt is inversely proportional to BLyS's expression. We evaluated data from ΔCt analysis observing that mRNA levels of BLyS in eGFRlow (6.193±1.787) were higher than those from eGFRhigh (7.564±2.326), with a statistically significant difference between groups (p=0.0288).eGFRloweGFRhigh BLyS (ΔCt)6.193±1.7877.564±2.326p=0.0288ConclusionsIn the present cross-sectional study, increased levels of BLyS were observed in patients with eGFR ≤60. These gene expression results might be linked to B cell activation and proliferation in kidney and thus in urine samples. Combination of eGFR and BLyS appears to be a good biomarker.References Rahman A. Can measuring urinary biomarkers improve the management of lupus nephritis? Arthritis Research & Therapy 2012, 14:127.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16; 130 (6):461–70.Phatak S, Chaurasia S, Mishra SK, Gupta R, Agrawal V, Aggarwal A, Misra R. Urinary B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL): potential biomarkers of active lupus nephritis. Clin Exp Immunol. 2016....
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