Low-dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long-term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.
The FE NGAL/FE protein ratio is a reliable marker of disease activity in patients with SLE and could be used as an indicator of response to therapy, although further studies are required to confirm these results.
Thirty-six MMF-treated patients (51%) remained in CR, and 23 (33%) failed treatment at last follow-up. Time to treatment failure was associated with persistent hypoalbuminaemia (hazard ratio (HR) = 0.87; 95%CI, 0.81-0.95; P = 0.001), higher proteinuria (HR = 1.29; 95%CI, 1.03-1.62; P = 0.030) and fewer early responses (HR 0.28; 95%CI, 0.10-0.77; P = 0.014). Renal relapse occurred in 24 (34%) patients. Time to flare was associated with persistent anti-dsDNA titres (HR = 1.001; 95%CI, 1.001-1.003; P = 0.005) and younger age at inclusion (HR = 0.36; 95%CI, 0.14-0.90; P = 0.029). Tacrolimus was added to 17 (24%) patients. A significant reduction of proteinuria was already observed at 3 months (P = 0.002). After 2 years follow-up, 12 (70%) of them achieved clinical response (six CR and six PR). Conclusions. MMF is an effective treatment for LN. Combination therapy with tacrolimus is an effective and safe alternative for MMF-resistant patients.
The association of common variable immunodeficiency (CVID) and Systemic Lupus Erythematosus (SLE) is infrequent. Mannose-binding lectin (MBL) has been shown to play a role in CVID and SLE. The purpose of this study is to describe two cases of CVID who presented as SLE and also evaluate the presence of MBL polymorphisms and MBL serum levels in those patients.In both patients, SLE was the first manifestation of CVID. In these patients the SLE immunological markers and disease activity disappeared after the development of CVID. They carried the very infrequent MBL haplotype 4Q-57Glu. One of them had a homozygous genotype, whereas the other patient was heterozygous and also presented the haplotype 4P-57Glu that had never been previously detected. Interestingly, this last patient was presenting frequent respiratory tract infections, developed brochiectasis and had low levels of circulating MBL.These results may support the role of MBL in the development of autoimmunity in CVID. Further genetic studies are needed to clarify the role of the MBL polymorphisms in the development of autoimmunity in CVID.
At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient’s long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis. NRP-1 is increased in kidney biopsies of LN. In this work we were interested in determining whether urinary NRP-1 levels could be a biomarker of clinical response in LN. Our results show that patients with active LN have increased levels of urinary NRP-1. When patients were divided according to clinical response, responders displayed higher urinary and tissue NRP-1 levels at the time of renal biopsy. Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1, and VEGFA protein levels, showed NRP-1 to be an independent predictor for clinical response. In addition, in vitro studies suggest that NRP-1could promote renal recovery through endothelial proliferation and migration, mesangial migration and local T cell cytotoxicity. Based on these results, NRP-1 may be used as an early prognostic biomarker in LN.
BackgroundLupus nephritis (LN) affects up to 50% of patients with SLE and is a major cause of morbidity, despite modern therapeutic approaches [1,2]. To date, renal biopsy is still the gold standard for diagnosing and classifying the degree of renal inflammation and scarring, but its invasiveness makes it unsuitable for serial monitoring. A novel biomarker to predict the evolution of renal inflammatory injury is still needed. Neuropilin-1 (NRP-1) has important functions in adult tissues, being involved in axonal guidance, vascular endothelial sprouting, regeneration and organ repair and immunosupression [3].ObjectivesEvaluate the protein and expression levels of NRP-1 at the time of the renal flare in patients with lupus nephritis and determine whether they could predict the disease progression.MethodsUrine and serum of 70 patients with LN with nephrotic proteinuria, 25 patients with chronic non-lupus related nephopathy, and 25 healthy controls were analyzed by qPCR-RT and ELISA to determinate the levels of mRNA/protein of NRP-1. Immunohistochemistry of protein levels were done in renal biopsy (N=5). Urine and serum from 39 other patients with LN with nephrotic proteinuria were collected prospectively during two years.ResultsIncreases in mRNA expression and protein concentration of NRP-1 were identified in urine samples of LN patients in flare compared with the different control groups. However, significant NRP-1 levels were found in LN patients that gone into remission compared with patients in non-remission after one year of treatment (p<0.0001). Urinary VEGFA, VEGFR1, VEGFR2 and SEMA3A mRNA and protein levels were also determinate. Results were confirmed with immunohistochemistry in renal biopsies (N=5). We observed a strong correlation with NRP-1 protein levels and VEGFA protein levels (r=0.466, p<0.0001). Areas under the receiver operating characteristic curve of urinary NRP-1 and VEGFA protein levels to distinguish between remission and non-remission patients were 0.8384 and 0.7706, respectively (Figure 1). In a prospective study (N=39), urinary protein NRP-1 and VEGFA levels decreased in LN patients going to complete remission; but no those with non-response that maintain their low levels during all the follow-up.ConclusionsFor first time, we demonstrate that urinary levels of NRP-1 might reflect the evolution of renal inflammatory injury and could be used as novel biomarker to predict the recovery of LN.References Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003;82:299–308.Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum.2003;48:3253–65.Gagnon ML, Bielenberg DR, Grechtman Z, et al. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expressi...
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