Effect of Autoantibodies to Erythropoietin Receptor in Systemic Lupus Erythematosus with Biopsy-proven Lupus Nephritis

Hara, Akinori; Furuichi, Kengo; Yamahana, Junya; Yasuda, H; Iwata, Yasunori; Sakai, Norihiko; Shimizu, Miho; Kaneko, Shuichi; Wada, Takashi

doi:10.3899/jrheum.151430

Cited by 16 publications

(15 citation statements)

References 27 publications

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“… 12 In addition, a recent study revealed that anti-EPOR antibodies were associated with overall disease activity and the decline of renal function in patients with systemic lupus erythematosus. 13 …”

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confidence: 99%

Clinical and Pathological Significance of Autoantibodies to Erythropoietin Receptor in Type 2 Diabetic Patients With CKD

Hara

Furuichi

Koshino

et al. 2018

Kidney International Reports

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IntroductionWe examined the impact of autoantibodies on the erythropoietin receptor (EPOR) in type 2 diabetic patients with chronic kidney disease (CKD).MethodsA total of 112 Japanese patients with type 2 diabetes who had CKD were enrolled in this study and followed for a mean of 45 months. Sera from these patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent assays.ResultsAnti-EPOR antibodies were detected in 26 patients (23%). Anti-EPOR antibodies were associated with low hemoglobin concentrations and decreased renal function. In patients with biopsy-proven diabetic nephropathy, anti-EPOR antibodies were associated with increased levels of interstitial inflammation. A decrease in renal function was observed more frequently in patients with antibodies than in those without antibodies, and the presence of the antibodies together with well-known clinical parameters, including proteinuria and low glomerular filtration rate, was a significant risk factor for end-stage renal disease. In human tubular epithelial HK-2 cells, IgG fractions containing anti-EPOR antibodies upregulated the expression of monocyte chemoattractant protein-1 mRNA under a high concentration of glucose.ConclusionAnti-EPOR antibodies might be involved in the progression of renal lesions and in the impaired erythropoiesis in type 2 diabetic patients with CKD. Furthermore, the presence of anti-EPOR antibodies may be an additional predictor for end-stage renal disease in type 2 diabetes.

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confidence: 99%

Clinical and Pathological Significance of Autoantibodies to Erythropoietin Receptor in Type 2 Diabetic Patients With CKD

Hara

Furuichi

Koshino

et al. 2018

Kidney International Reports

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“…Importantly, mice selectively lacking EPO-R in T cells are resistant to EPO inhibitory effects on Th17 cells, further indicating that EPO also directly inhibits Th17 cell induction in this in vivo model. Reduced EPO concentration or the presence of antibodies against EPO or EPO-R are common in human systemic lupus erythematosus (46) and correlate with disease severity (47,48), along with percentages of Th17 cells (49), supporting a causal link among low EPO/EPO-R signaling, Th17 cell induction, and systemic lupus erythematosus activity in affected patients.…”

Section: Discussionmentioning

confidence: 97%

Erythropoietin inhibits SGK1-dependent Th17 cell induction and Th17 cell–dependent kidney disease

Donadei¹,

Angeletti²,

Cantarelli³

et al. 2019

JCI Insight

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“…It is possible that lower doses of EPO or different times of administration may be more effective for clinical disease especially since new work suggests a role for EPO and EPOR autoantibodies for disease progression (282, 283). Additional studies suggest that low concentrations of EPO may be beneficial to the cardiovascular system (284–286) and also may benefit neurological function.…”

Section: Future Perspectivesmentioning

confidence: 99%

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

Maiese¹

2016

CNR

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Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. Yet, the biological and clinical outcome of these pathways can be complex especially with oversight of cell death mechanisms that involve apoptosis and autophagy. Growth factors, and in particular erythropoietin (EPO), are one avenue under consideration to implement control over cell death pathways since EPO can offer potential treatment for multiple disease entities and is intimately dependent upon mTOR signaling. In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies.

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Effect of Autoantibodies to Erythropoietin Receptor in Systemic Lupus Erythematosus with Biopsy-proven Lupus Nephritis

Abstract: The present study suggests that anti-EPOR antibodies might be involved in overall disease activity and active renal lesions, as well as in the impaired erythropoiesis in patients with SLE with LN. Further, the levels of anti-EPOR antibodies may be an additional predictor for renal injury.

Cited by 16 publications

References 27 publications

Clinical and Pathological Significance of Autoantibodies to Erythropoietin Receptor in Type 2 Diabetic Patients With CKD

Clinical and Pathological Significance of Autoantibodies to Erythropoietin Receptor in Type 2 Diabetic Patients With CKD

Erythropoietin inhibits SGK1-dependent Th17 cell induction and Th17 cell–dependent kidney disease

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

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