Treatment of systemic lupus erythematosus–associated type B insulin resistance syndrome with cyclophosphamide and mycophenolate mofetil

Gehi, Anil K.; Webb, Allison; Nolte, M.; Davis, John C.

doi:10.1002/art.10879

Cited by 39 publications

(21 citation statements)

References 29 publications

(26 reference statements)

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“…TNF-α and IL-6 however was increased in our SLE patients with renal involvement, but this increase was not statistically significant. The borderline elevation of these cytokines was probably due to administration of immunosuppressive drugs to our patients which has also been reported by Gehi et al [53]. …”

Section: Discussionsupporting

confidence: 58%

MiRNA and mRNA Profiling in Systemic Lupus Reveals a Novel Set of Cytokine - Related miRNAs and their Target Genes in Cases With and Without Renal Involvement

Ghods

Sarikaya

Arda

et al. 2017

Kidney Blood Press Res

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Background/Aims: MiRNAs transpire as promising elements in molecular medicine for the identification of new diagnostic, prognostic and targeting therapeutic biomarkers. This study consisted of four steps: First, to investigate one or a group of specific diagnostic miRNAs for Systemic Lupus Erythematosus (SLE) disease in patients with and without renal involvement, second, to identify cytokines genes’ expression profiling, third, comparing the profiles with related amounts in the serum and finally, to study target-gene-mediated functional roles of miRNAs, which have been correlated to disease development and progression. Methods: In order to use in microarray assays total RNA and miRNAs were isolated from blood and serum samples that were obtained from 16 SLE patients (9 with renal involvement and 7 without renal involvement). Taking coexistence of factors such as hypocomplementemia, positive ANA and anti-DNA into account, obtained data were processed. For each differentially expressed miRNA, potential target genes were predicted by microRNAorg, TargetScan and PITA prediction tools. Obtained mRNA profiling data were interrogated for the target genes. MiRNA and mRNA microarray results were confirmed by QRT-PCR. Finally, the amounts of cytokines were measured by multiplex ELISA method. Results: The results of study showed that among differentially expressed miRNAs in SLE patients with renal involvement compared to those without renal involvement, hsa-miR-766-3p, may play pivotal roles in PI3K-AKT-mTOR pathway. In addition according to the obtained data it is suggested that blood-borne proinflammatory cytokines such as IL-4, IL-6 and TNF-α alongside with disease stage and severity may contribute to this differential expression of these miRNA which may be leading to insulin resistance. Finally, hsa-miR-621, which was differentially expressed in hypertensive SLE patients without renal involvement and a positive ANA test with its predicted target gene “Kallikrein-related peptidase 9” may play a role in the pathophysiology of hypertension in SLE. Conclusions: We reported some human miRNAs which were differentially expressed in SLE patients according to disease activity and renal involvement. Larger studies are necessary to confirm our findings and detect further biomarkers.

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Section: Discussionsupporting

confidence: 58%

MiRNA and mRNA Profiling in Systemic Lupus Reveals a Novel Set of Cytokine - Related miRNAs and their Target Genes in Cases With and Without Renal Involvement

Ghods

Sarikaya

Arda

et al. 2017

Kidney Blood Press Res

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“…Systemic inflammation and anti-insulin antibodies could promote the development of insulin resistance (38,39), with the ensuing dyslipidemia, hypertension, and increase in body weight. Also, endothelial damage and dysfunction, induced by lupus systemic inflammation, can be accompanied by overproduction of the vasoconstrictors thromboxane and endothelin 1, leading to elevation of BP (40).…”

Section: Discussionmentioning

confidence: 99%

Recent corticosteroid use and recent disease activity: Independent determinants of coronary heart disease risk factors in systemic lupus erythematosus?

Karp

Abrahamowicz

Fortin

et al. 2008

Arthritis & Rheumatism

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“…In rare clinical cases, patients with SLE develop antibodies to the insulin receptor, which cause insulin resistance (type B insulin resistance). 19 Independent of these case studies, currently available data suggest that humans with SLE are at an increased risk to develop insulin resistance and obesity. For example, it has been reported that individuals with SLE have significantly increased body mass index at a 10-year follow-up compared with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance and Obesity in a Mouse Model of Systemic Lupus Erythematosus

2006

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Abstract-Accumulating data indicate that metabolic syndrome is an inflammatory condition. Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with nephritis and cardiovascular disease. Evidence suggests that individuals with SLE are at risk for developing insulin resistance; however, this has not been directly examined. Using an established mouse strain with SLE (NZBWF1), we examined whether SLE is associated with increased body weight and fat deposition. Mean arterial pressure was significantly increased (140Ϯ4 versus 114Ϯ2 mm Hg; nՆ5) in SLE mice by 36 weeks of age compared with control mice (NZW/LacJ). Body weight in SLE mice was higher at each age compared with controls by 12%, 22%, and 34% (nϾ30). Visceral adipose tissue weight was increased in SLE by 44%, 74%, and 117% at 8, 20, and 36 weeks, respectively (nՆ12 etabolic syndrome can be characterized by a group of metabolic risk factors that includes central obesity, insulin resistance, dyslipidemia, increased blood pressure, and endothelial dysfunction. 1 Individuals with metabolic syndrome are at a markedly increased risk for developing hypertension and renal disease. Recent evidence indicates that inflammatory cytokines are elevated in patients with metabolic syndrome, 2-4 thus suggesting a role for chronic inflammation as an underlying mechanism for progression of this disease.Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that predominantly affects women during their reproductive years. The presence of autoantibodies (typically antinuclear antibodies) is used diagnostically, and although SLE can influence many organ systems, the skin, joints, and kidneys are typically affected. Like metabolic syndrome, a large percentage of individuals with SLE are hypertensive. Evidence suggests that individuals with SLE are also at increased risk for developing insulin resistance 5 and changes in body mass composition 6 ; however, this has not been adequately examined.The purpose of the present study was to test whether the progression of SLE is associated with changes in body composition, insulin sensitivity, and other characteristics of the metabolic syndrome. To examine this, we used a genetic mouse model of SLE (NZBWF1) that exhibits many features of human SLE, including a complex genetic origin, a bias for the female sex, immune complex glomerulonephritis, and the presence of antinuclear antibodies. We reported recently that these mice have hypertension and impaired endothelialdependent relaxation. 7 The results of the present study show that NZBWF1 mice also have several other characteristics of the metabolic syndrome that may contribute to the hypertension, including central obesity, insulin resistance, and hyperleptinemia. These data show that the NZBWF1 strain may be an important model to study the effects of obesity and insulin resistance on SLE-associated hypertension. Methods AnimalsFemale NZBWF1 (SLE) and NZW/LacJ (control) obtained from Jackson Laboratories (Bar Harbor, ME) were maintained on a 12-hour light/d...

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Treatment of systemic lupus erythematosus–associated type B insulin resistance syndrome with cyclophosphamide and mycophenolate mofetil

Cited by 39 publications

References 29 publications

MiRNA and mRNA Profiling in Systemic Lupus Reveals a Novel Set of Cytokine - Related miRNAs and their Target Genes in Cases With and Without Renal Involvement

MiRNA and mRNA Profiling in Systemic Lupus Reveals a Novel Set of Cytokine - Related miRNAs and their Target Genes in Cases With and Without Renal Involvement

Recent corticosteroid use and recent disease activity: Independent determinants of coronary heart disease risk factors in systemic lupus erythematosus?

Insulin Resistance and Obesity in a Mouse Model of Systemic Lupus Erythematosus

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