Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts

Nienhuis, Hans L A; Leeuw, de Karina; Bijzet, J.; Smit, Andries J.; Schalkwijk, Casper G.; Graaff, Reindert; Kallenberg, Cornelis; Bijl, Marc

doi:10.1093/rheumatology/ken302

Cited by 50 publications

(63 citation statements)

References 46 publications

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“…In this particular study, skin autofluorescence was closely correlated with collagen-linked fluorescence and with the specific AGEs, with correlation coefficients greater than 0.40. However, 2 subsequent studies did not show significant association between skin autofluorescence and plasma concentration of AGEs in patients with type 1 diabetic mellitus (n = 68) [20] or systemic lupus erythematosus (n = 9) [26]. These latter observations are in line with the overall results of our study.…”

Section: Discussionsupporting

confidence: 92%

A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

Liu

Huang

Cheng

et al. 2016

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Background: We compared skin and plasma measurements of advanced glycation end products (AGEs), with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension. Methods: Skin AGE accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using the SphygmoCor system (Sydney, Australia). Results: The 218 participants (96 [44.0%] men, mean age 51.9 years) had a mean skin autofluorescence of 1.89 arbitrary units, plasma AGE concentration of 4.47 μg/ml, and cfPWV of 8.0 m/s. Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients (n = 31, r = 0.37, p = 0.04) but not in subjects with normoglycemia (n = 187, r = -0.05, p = 0.48). Nonetheless, both measurements were significantly (p ≤ 0.001) higher in men (2.00 arbitrary units and 6.73 μg/ml, respectively) than women (1.81 arbitrary units and 3.60 μg/ml, respectively) and in diabetic or prediabetic (2.03 arbitrary units and 6.61 μg/ml, respectively) than normoglycemia subjects (1.87 arbitrary units and 4.17 μg/ml, respectively), but similar in hypertensive (n = 105) and normotensive subjects (n = 113, p ≥ 0.35). In adjusted multiple regression analyses, plasma AGE concentration, but not skin autofluorescence (p ≥ 0.37), was significantly associated with cfPWV in all subjects (β 0.44 m/s for each 10-fold increase; p = 0.04) and in subgroups of men and diabetes and prediabetes (β 0.12-0.55 m/s for each 10-fold increase; p ≤ 0.02). Conclusions: Although skin and plasma AGEs were similarly associated with gender and diabetes or prediabetes, they might measure something different and have different clinical relevance, such as for arterial stiffness.

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Section: Discussionsupporting

confidence: 92%

A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

Liu

Huang

Cheng

et al. 2016

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“…RAGE is upregulated in SLE in the acute phase of glomerular injury in lupus nephritis (39). The spliced extracellular domain of RAGE (soluble RAGE) accumulates in the blood of SLE patients, and RAGE expression correlated with SLE disease severity (40). In addition, we demonstrated here that RAGE has high affinity to major pathogenic molecules (e.g., C3a, DNA, HMGB1, AGEs, C3a/DNA complex, and HMGB1/DNA complex) found in SLE.…”

Section: Discussionmentioning

confidence: 60%

Complement C3a, CpG Oligos, and DNA/C3a Complex Stimulate IFN-α Production in a Receptor for Advanced Glycation End Product-Dependent Manner

Ruan

Winkler

et al. 2010

The Journal of Immunology

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The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor implicated in a number of diseases including autoimmune diseases. To further understand the pathogenic mechanism of RAGE in these diseases, we searched for additional ligands. We discovered that C3a bound to RAGE with an EC50 of 1.9 nM in an ELISA, and the binding was increased both in magnitude (by >2-fold) and in affinity (EC50 70 pM) in the presence of human stimulatory unmethylated cytosine-guanine-rich DNA A (hCpGAs). Surface plasmon resonance and fluorescence anisotropy analyses demonstrated that hCpGAs could bind directly to RAGE and C3a and form a ternary complex. In human PBMCs, C3a increased IFN-α production in response to low levels of hCpGAs, and this synergy was blocked by soluble RAGE or by an Ab directed against RAGE. IFN-α production was reduced in response to mouse CpGAs and C3a in RAGE−/− mouse bone marrow cells compared wild-type mice. Taken together, these data demonstrate that RAGE is a receptor for C3a and CpGA. Through direct interaction, C3a and CpGA synergize to increase IFN-α production in a RAGE-dependent manner and stimulate an innate immune response. These findings indicate a potential role of RAGE in autoimmune diseases that show accumulation of immunostimulatory DNA and C3a.

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“…Furthermore, when compared with quiescent SLE, the blood sRAGE levels were significantly increased during active disease in the Dutch study. [31] This difference might be attributed to the fact that the latter study only included 10 SLE patients (9 Caucasians and 1 Asian). Also, the usage of different medication regimes could have been an influential factor.…”

Section: Discussionmentioning

confidence: 98%

“…[29,30] To date, only two studies have investigated the serum sRAGE levels in SLE patients, and they reported conf licting results. [31,32] However, experimental animal models have provided encouraging results about the therapeutic role of sRAGE. [33,34] All of these investigations indicate that it could represent a future therapeutic target in chronic inflammatory diseases.…”

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confidence: 99%

A Soluble Receptor for Advanced Glycation End Product Levels in Patients with Systemic Lupus Erythematosus

2013

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Amaç: Bu çalışmada sistemik lupus eritematöz (SLE) olan hastalarda ileri glikasyon son ürünlerinin çözünür reseptörünün (sRAGE) plazma düzeyleri değerlendirildi ve bu düzeylerin farklı klinik, laboratuvar ve tedavi parametreleri ile olan ilişkisi araştırıldı. Hastalar ve yöntemler:Çalışmaya toplam 120 SLE hastası (111 kadın, 9 erkek) ve yaş ve cinsiyet eşleştirmeli 40 sağlıklı kontrol alındı. Plazma sRAGE düzeyleri, ticari olarak satılan enzim bağlı immünosorbent test (ELISA) kiti kullanılarak ölçüldü. Plazma sRAGE düzeyleri ve SLE'nin klinik ve laboratuvar özellikleri arasındaki muhtemel ilişki de değerlendirildi. Farklı tedavi yöntemlerinin sRAGE plazma düzeyleri üzerindeki etkinliği incelendi. Bulgular: Sağlıklı kontrollere kıyasla, SLE hastalarının plazma sRAGE düzeyleri anlamlı düzeyde daha düşüktü (p=0.003). Cilt döküntüsü veya serozit olan hastaların sRAGE düzeyleri, olmayanlara kıyasla anlamlı düzeyde daha yüksekti (sırasıyla p=0.036 ve p=0.017). Daha uzun süre tedavi edilen SLE hastalarının sRAGE düzeyleri, daha kısa süreli tedavi edilenlerden daha yüksekti (p=0.000). Kortikosteroid ile tedavi edilen ve kombine tedavi edilen hastalar arasında düzey açısından anlamlı bir fark yoktu (p=0.89). sRAGE düzeyleri ve total beyaz kan hücre (WBC) sayımı (r=-0.356; p=0.003), lenfosit (r=0.341; p<0.001) ve nötrofil (r=0.289; p=0.006) arasında anlamlı negatif bir ilişki vardı.Sonuç: Çalışmamızda SLE hastalarında sRAGE plazma düzeylerinin anlamlı derecede azaldığı bulundu. Bu da, sRAGE düzeylerinin hastalığın patogenezinde muhtemel bir rol oynadığını göstermektedir.Anahtar sözcükler: İleri glikasyon son ürünü; reseptör; sistemik lupus eritematöz. Objectives:In this study, we aimed to evaluate the plasma levels of a soluble receptor for advanced glycation end products (sRAGE) in patients with systemic lupus erythematosus (SLE) and to investigate their relationship with different clinical, laboratory, and therapeutic parameters. Patients and methods:A total of 120 patients with SLE (111 females, 9 males) and 40 age-and gender-matched healthy controls were included. The plasma sRAGE levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The possible relationship between plasma sRAGE levels with SLE clinical and laboratory characteristics were also assessed. The effectiveness of different therapeutic modalities on plasma sRAGE levels was analyzed. Results:The SLE patients had significantly lower plasma levels of sRAGE than the healthy controls (p=0.003). The patients with a skin rash or serositis had significantly higher sRAGE levels than those without (p=0.036 and p=0.017, respectively). The SLE patients who were treated over a longer period of time showed higher levels of sRAGE than those treated for shorter periods (p=0.000). No significant difference in levels was found among the patients treated with corticosteroids and those treated with combined therapy (p=0.89). There was a significant negative correlation between the sRAGE level and the total white blood cell (WBC) count (...

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Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts

Cited by 50 publications

References 46 publications

A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

Complement C3a, CpG Oligos, and DNA/C3a Complex Stimulate IFN-α Production in a Receptor for Advanced Glycation End Product-Dependent Manner

A Soluble Receptor for Advanced Glycation End Product Levels in Patients with Systemic Lupus Erythematosus

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