Controversies in Systemic Lupus Erythematosus 2021
Sabrina PortaAntoine EnfreinFrédéric HoussiauMercedes GarcìaRichard FurieBrad H. RovinGraciela S. AlarcónBernardo A. Pons‐EstelGuillermo J. Pons‐Estel
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Abstract:
Lupus nephritis (LN) affects about a third of patients with systemic lupus erythematosus. Although the use of conventional therapy has significantly improved the prognosis of LN, the response to treatment remains suboptimal, with high rates of relapse and the occurrence of end-stage kidney disease. The implementation of new diagnostic and treatment strategies aimed at improving these outcomes represents a necessary paradigm shift in the management of LN.Herein, we discuss different points of view regarding these still unresolved issues; these comments represent a debate that took place during the virtual congress of the Pan American League of Associations for Rheumatology (PANLAR) and which was organized by the PANLAR Lupus Study Group, GLADEL (Grupo Latino Americano De Estudio del Lupus) on August 15, 2021.Minimal change disease
Glomerulopathy
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Objective To investigate the evaluation of extrarenal activity in lupus nephritis patients with end stage renal disease (ESRD).Methods 69 patients who received maintenance dialysis at the Second Affiliated Hospital of Lanzhou Medical College from 1990～1998 were studied retrospectively. Results 24 patients (35%) had clinical lupus activity before dialysis. But during the first year of dialysis, 39 patients (57%) experienced lupus activity, and decreased for years thereafter (P0.05).serologic abnormalities improved gradually over time (P0.05). Conclusions Extrarenal lupus activity in lupus nephritis after ESRD is not common, especially during the first year of dialysis,which can be relieved by using of short -term coticoid.
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"Renal biopsy in patients with lupus: Not just lupus nephritis!." Ultrastructural Pathology, 41(1), p. 98
Renal pathology
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Background:
Vitamin D (25OHD) has immunomodulatory properties that can play a major role in patients with active lupus or lupus nephritis. His immunomodulatory function could be influenced by demographic factors, comorbidities (Charlson score), bone supplements, and other features.Objectives:
We explored the association between the best 25OHD cut-off points and specific clinical features that were present in patients with active lupus or lupus nephritis.Methods:
A retrospective descriptive research using clinical registers of patients diagnosed with systemic erythematosus lupus, attended in two rheumatology clinics was performed. A decisions tree model was used to identify the best cut-off points of 25OHD [ng/mL] and clinical features associated with active lupus (SLEDAI-2k >6) or lupus nephritis.Results:
We identified 81 patients, median age 41 years, women 91.3%. Active lupus and lupus nephritis were present in 69.1% and 29.6%, respectively. Median 25OHD was 26.49, without a difference at comparing with active lupus patients 24.85, but lower in lupus nephritis patients 21.50 (p: 0.015). Lupus nephritis was absent in patients with 25OHD cut-off points >38.8 (alone) or ≤38.8 if they were older than >57 years. Active lupus was always present in patients ≤44 years with 1. High comorbidity or 2. Low comorbidity plus cut-off point 25OHD >35; in >44 years, both a euthyroid state and the absence of bone supplements were present in patients with active lupus.Conclusion:
Exist a strong relationship between vitamin D levels and LES activity.References
[1] American College of Rheumatology. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999 Sep;42(9):1785-96 [2] Simioni J, Heimovski F, Skare T. On lupus, vitamin D and leukopenia. 2016;56(3):206-211. [3] Guzman R.A, Piñeros L.G, Theran A, Flechas J, Mejía M. AB0795 Hypovitaminosis D and Calcium Intake of Adult Population in Bogota (DICAVITD). Ann Rheum Dis 2016;75:1175-. 1176.Acknowledgement:
To Fundación Universitaria Juan N. CorpasDisclosure of Interests:
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The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.
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Anti-ficolin-2 Antibody: Could it be a Predictor of Proliferative Lupus Nephritis in Lupus Patients?
Background: Nephritis is a challenging domain of systemic lupus erythematosus (SLE).There is a growing need for identification of a non-invasive marker for diagnosing and monitoring nephritis.Objective: To explore the relevance of using anti-ficolin-2 antibody (Anti-FCN2) as a biomarker for detecting lupus nephritis (LN), and its relation to renal biopsy histopathology and disease activity.Patients and Methods: Sixty SLE patients were compared to 30 apparently healthy individuals.Thirty of the patients were LN patients (documented by a recent renal biopsy).Full history, examination and laboratory investigations were done.Activity was assessed by SLE disease activity index (SLEDAI) score, and Anti-FCN2 titer was measured by enzyme-linked immunosorbent assay technique (ELISA).Results: Forty-four of our SLE patients were in disease activity by SLEDAI score.Anti-FCN2 titer was significantly higher among SLE patients compared to control group (p value <0.001).It was also higher among patients with high disease activity compared to those with low disease activity and cutoff value was at 37 ng/ml (p value is <0.001).Anti-FCN2 titer was significantly higher among patients with LN compared to those without LN (p value is <0.001) with best cutoff value at 72.50 ng/ml.Regarding LN patients, it was significantly higher among patients with proliferative changes than LN patients with non-proliferative changes (p value is 0.05) with best cutoff value at 155 ng/ml.Conclusion: Anti-FCN2 shows promising results as a biomarker for lupus disease activity, especially regarding LN and proliferative changes.Further longitudinal studies on larger samples are needed to confirm.
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This article reviews the commonly used murine strains for studying lupus and lupus nephritis, including strains that develop lupus spontaneously, congenic strains, induced models of lupus, as well as genetically engineered mouse models of lupus bearing transgenes or knockouts. The review then summarizes the main cellular and molecular pathways that lead to the pathogenesis of this autoimmune disease, including autoantibodies. Finally, it concludes with therapeutic insights gained from using mouse models of lupus. To sum, much of what we have learned about lupus has arisen from studying mouse models of the disease, and the laboratory mouse continues to be one of the best tools for studying human SLE. Keywords: Lupus, animal models, nephritis, autoantibody, genetics.
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CSF-1, required for macrophage (Mø) survival, proliferation, and activation, is upregulated in the tubular epithelial cells (TECs) during kidney inflammation. CSF-1 mediates Mø-dependent destruction in lupus-susceptible mice with nephritis and, paradoxically, Mø-dependent renal repair in lupus-resistant mice after transient ischemia/reperfusion injury (I/R). We now report that I/R leads to defective renal repair, nonresolving inflammation, and, in turn, early-onset lupus nephritis in preclinical MRL/MpJ-Faslpr/Fas(lpr) mice (MRL-Fas(lpr) mice). Moreover, defective renal repair is not unique to MRL-Fas(lpr) mice, as flawed healing is a feature of other lupus-susceptible mice (Sle 123) and MRL mice without the Fas(lpr) mutation. Increasing CSF-1 hastens renal healing after I/R in lupus-resistant mice but hinders healing, exacerbates nonresolving inflammation, and triggers more severe early-onset lupus nephritis in MRL-Fas(lpr) mice. Probing further, the time-related balance of M1 "destroyer" Mø shifts toward the M2 "healer" phenotype in lupus-resistant mice after I/R, but M1 Mø continue to dominate in MRL-Fas(lpr) mice. Moreover, hypoxic TECs release mediators, including CSF-1, that are responsible for stimulating the expansion of M1 Mø inherently poised to destroy the kidney in MRL-Fas(lpr) mice. In conclusion, I/R induces CSF-1 in injured TECs that expands aberrant Mø (M1 phenotype), mediating defective renal repair and nonresolving inflammation, and thereby hastens the onset of lupus nephritis.
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