Soluble Receptor Level of Advanced Glycation (sRAGE) Products in Serum in Patients with Systemic Lupus Erythematosus:
Yıl 2024,
Cilt: 19 Sayı: 2, 29 - 34, 22.07.2024
Serdar Gök
,
Burak Okyar
,
Defne Ay Tuncel
,
Fatma İnanç Tolun
,
Filiz Alkan Baylan
,
Can Acıpayam
,
Adem Doğaner
,
Gözde Yıldırım Çetin
Öz
Objectives: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by antibody formation against nuclear autoantigens. A receptor for Advanced Glycation (RAGE) is produced by many immune system cells, such as neutrophils, macrophages, and T cells, and interacts with many classes of ligands. In light of these results, the level of sRAGE, the soluble form of RAGE, may be associated with disease activity. In light of this information, we aimed to evaluate whether there is a relationship between plasma sRAGE levels and SLE.
Materials and Methods: Eighteen patients diagnosed with SLE (M/F: 1/17) and twenty-one patients without any disease diagnosis (M/F: 2/19) were included as the control group. In these patients, plasma sRAGE level was measured by ELIZA method using an ELIZA (enzyme-linked immunosorbent assay) kit (BioVendor Research and Diagnostic Products). The data obtained were compared between the groups.
Results: The mean plasma sRAGE level was lower in patients with SLE than in healthy control patients but not statistically significant (p=0.966). Our study found a positive correlation between SLEDAI and sRAGE levels in patients with SLE (r=0.628, p=0.005). Although no significant correlation was found between patients with SLE, sRAGE levels were positively correlated between fourteen patients classified as active SLE and the control group.
Conclusions: In our study, we found that plasma sRAGE levels in patients with SLE were lower than in healthy controls, but plasma sRAGE levels in patients with active SLE were higher than plasma sRAGE levels in patients with inactive SLE. We hypothesized that reduced sRAGE levels in patients with SLE could be explained by the depletion of this soluble receptor. Our study differed from another similar study showing that blood sRAGE levels were higher in patients with SLE than in healthy controls. Blood sRAGE levels were significantly increased during active disease compared with patients with quiescent SLE.
Kaynakça
- Abdulahad DA, Westra J, Limburg PC, Kallenberg CG, Bijl M. HMGB1 in systemic lupus Erythematosus: Its role in cutaneous lesions development. Autoimmun Rev 2010;9: 661-5.
- Schmidt AM, Yan SD, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 2001;108:949-55.
- Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007;81: 1-5.
- Hreggvidsdottir HS, Ostberg T, Wahamaa H, Schierbeck H, Aveberger AC, Klevenvall L, et al. The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol 2009;86: 655-62.
- Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 2007;8: 492-502.
- Tian J, Avalos AM, Mao SY, Chen B, Senthil K, Wu H, et al. Toll-like receptor 9-dependent activation by NA containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 2007;8: 487-96.
- Tackey E, Lipsky PE, Illei GG. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus 2004;13: 339-43.
- Bianchi ME, Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev 2007;220: 35-46.
- Ma CY, Jiao YL, Zhang J, Yang QR, Zhang ZF, Shen YJ, et al. Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN-α and TNF-α in systemic lupus erythematosus. Rheumatol Int 2012;32: 395-402.
- Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JE. Diabetes and advanced glycoxidation end products. Diabetes Care 2006;29: 1420-32.
- Ritthaler U, Deng Y, Zhang Y, Greten J, Abel M, Sido B, et al. Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease. Am J Pathol. 1995 Mar;146(3):688-94.
- Soulis T, Thallas V, Youssef S, Gilbert RE, McWilliam BG, Murray-McIntosh RP, Cooper ME. Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury. Diabetologia. 1997 Jun;40(6):619-28.
- Zhang F, Kent KC, Yamanouchi D, et al. Anti-receptor for advanced glycation end products therapies as novel treatment for abdominal aortic aneurysm. Ann Surg 2009;250(3):416–23.
- Nowak A, Przywara-Chowaniec B, Damasiewicz-Bodzek A, Blachut D, Nowalany-Kozielska E, Tyrpień Golder K. Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE). Cells. 2021 Dec 13;10(12):3523.
- Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, et al. Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease. Neurobiol Aging 2011;32: 763-77.
- Donato R. S100: a multigenic family of calcium-modulated proteins of the EFhand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 2001;33: 637-68.
- Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W,Sunderkotter C, et al. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticularonset juvenile rheumatoid arthritis. Arthritis Rheum 2000;43: 628-37.
- Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004;50: 3762-71.
- Soyfoo MS, Roth J, Vogl T, Pochet R, Decaux G. Phagocyte-specific S100A8/A9 protein levels during disease exacerbations and infections in systemic lupus erythematosus. J Rheumatol 2009;36: 2190-4.
- Tam XHL, Shiu SWM, Leng L, Bucala R, Betteridge DJ, Tan KCB. Enhanced expression of receptor for advanced glycation endproducts is associated with low circulating soluble isoforms of the receptor in Type 2 diabetes. Clin Sci (Lond) 2011;120(2):81–89.
- Hammady MMR, Khashali SEL, Halim HA, Rashed L, Hussein M. Soluble receptor for advanced glycation end products (sRAGE) innon-diabetic hemodialysis patients and chronic kidney disease. Med J Cairo Univ 2012;80: 69–75.
- Stewart C, Cha S, Caudle RM, Berg K, Katz J. Decreased levels of soluble receptor for advanced glycation end products in patients with primary Sjogren's syndrome. Rheumatol Int 2008;28: 771-6.
- Islam S, Mir AR, Abidi M, Talha M, Zafar A, Habib S, et al. Methylglyoxal modified IgG generates autoimmune response in rheumatoid arthritis. Int J Biol Macromol. 2018 Oct 15;118(Pt A):15-23.
- Sirois CM, Jin T, Miller AL, Bertheloot D, Nakamura H, Horvath GL, et al. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA. J Exp Med. 2013 Oct 21;210(11):2447-63.
- Hofmann MA, Drury S, Hudson BI, Gleason MR, Qu W,Lu Y, et al. RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun 2002;3: 123-35.
- Abdulahad DA, Westra J, Bijzet J, Limburg PC, Kallenberg CG, Bijl M. High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus. Arthritis Res Ther 2011;13:R71.
- Li J, Xie H, Wen T, Liu H, Zhu W, Chen X. Expression of high mobility group box chromosomal protein 1 and its modulating effects on downstream cytokines in systemic lupus erythematosus. J Rheumatol 2010;37: 766–75.
- Ma CY, Jiao YL, Zhang J et al. Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN‐alpha and TNF‐alpha in systemic lupus erythematosus. Rheumatol Int 2012;32: 395–402.
- Nienhuis HL, de Leeuw K, Bijzet J et al. Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts. Rheumatology (Oxford) 2008;47: 1554–8.
- Tan KC, Shiu SW, Chow WS, Leng L, Bucala R, Betteridge DJ. Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes. Diabetologia 2006;49: 2756–62.
- Kalousová M, Hodková M, Kazderová M, Fialová J, Tesar V, Dusilová-Sulková S, Zima T. Soluble receptor for advanced glycation end products in patients with decreased renal function. Am J Kidney Dis. 2006 Mar;47(3):406-11.
- Forbes JM, Thorpe SR, Thallas Bonke V et al. Modulation of soluble receptor for advanced glycation end products by angiotensin‐converting enzyme‐1 inhibition in diabetic nephropathy. J Am Soc Nephrol 2005;16: 2363–72.
- Chavakis T, Bierhaus A, Al Fakhri N et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 2003;198:1507–15.
Sistemik Lupus Eritematozuslu Hastalarda Serumda Gelişmiş Glikasyon Ürünlerinin Çözünür Reseptörü (SRAGE) Seviyesi
Yıl 2024,
Cilt: 19 Sayı: 2, 29 - 34, 22.07.2024
Serdar Gök
,
Burak Okyar
,
Defne Ay Tuncel
,
Fatma İnanç Tolun
,
Filiz Alkan Baylan
,
Can Acıpayam
,
Adem Doğaner
,
Gözde Yıldırım Çetin
Öz
Amaç: Sistemik Lupus Eritematozus (SLE) nükleer otoantijenlere karşı antikor oluşumu ile karakterize otoimmün bir hastalıktır. İleri Glikasyon Reseptörü (RAGE) nötrofiller, makrofajlar ve T hücreleri gibi birçok bağışıklık sistemi hücresi tarafından üretilir ve birçok ligand sınıfı ile etkileşime girer. Bu sonuçlar ışığında, RAGE'nin çözünebilir formu olan sRAGE seviyesi hastalık aktivitesi ile ilişkili olabilir. Bu bilgiler ışığında, plazma sRAGE düzeyleri ile SLE arasında bir ilişki olup olmadığını değerlendirmeyi amaçladık.
Gereç ve Yöntem: SLE tanısı konmuş on sekiz hasta (E/K: 1/17) ve herhangi bir hastalık tanısı olmayan yirmi bir hasta (E/K: 2/19) kontrol grubu olarak çalışmaya dahil edildi. Bu hastalarda plazma sRAGE düzeyi ELIZA (enzyme-linked immunosorbent assay) kiti (BioVendor Research and Diagnostic Products) kullanılarak ELIZA yöntemi ile ölçüldü. Elde edilen veriler gruplar arasında karşılaştırıldı.
Bulgular: Ortalama plazma sRAGE düzeyi SLE hastalarında sağlıklı kontrol hastalarına göre daha düşüktü ancak istatistiksel olarak anlamlı değildi (p=0.966). Çalışmamızda SLE'li hastalarda SLEDAI ve sRAGE düzeyleri arasında pozitif bir korelasyon bulundu (r=0.628, p=0.005). SLE'li hastalar arasında anlamlı bir korelasyon bulunmamasına rağmen, aktif SLE olarak sınıflandırılan on dört hasta ile kontrol grubu arasında sRAGE düzeyleri pozitif korelasyon göstermiştir.
Sonuç: Çalışmamızda, SLE'li hastalarda plazma sRAGE düzeylerinin sağlıklı kontrollere göre daha düşük olduğunu, ancak aktif SLE'li hastalarda plazma sRAGE düzeylerinin inaktif SLE'li hastalardaki plazma sRAGE düzeylerinden daha yüksek olduğunu bulduk. SLE'li hastalarda sRAGE düzeylerindeki azalmanın bu çözünür reseptörün tükenmesi ile açıklanabileceğini varsaydık. Çalışmamız, SLE'li hastalarda kan sRAGE düzeylerinin sağlıklı kontrollere göre daha yüksek olduğunu gösteren benzer bir başka çalışmadan farklıydı. Kan sRAGE düzeyleri, aktif hastalık sırasında, sakin SLE hastalarına kıyasla önemli ölçüde artmıştır.
Kaynakça
- Abdulahad DA, Westra J, Limburg PC, Kallenberg CG, Bijl M. HMGB1 in systemic lupus Erythematosus: Its role in cutaneous lesions development. Autoimmun Rev 2010;9: 661-5.
- Schmidt AM, Yan SD, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 2001;108:949-55.
- Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007;81: 1-5.
- Hreggvidsdottir HS, Ostberg T, Wahamaa H, Schierbeck H, Aveberger AC, Klevenvall L, et al. The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation. J Leukoc Biol 2009;86: 655-62.
- Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 2007;8: 492-502.
- Tian J, Avalos AM, Mao SY, Chen B, Senthil K, Wu H, et al. Toll-like receptor 9-dependent activation by NA containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 2007;8: 487-96.
- Tackey E, Lipsky PE, Illei GG. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus 2004;13: 339-43.
- Bianchi ME, Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev 2007;220: 35-46.
- Ma CY, Jiao YL, Zhang J, Yang QR, Zhang ZF, Shen YJ, et al. Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN-α and TNF-α in systemic lupus erythematosus. Rheumatol Int 2012;32: 395-402.
- Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JE. Diabetes and advanced glycoxidation end products. Diabetes Care 2006;29: 1420-32.
- Ritthaler U, Deng Y, Zhang Y, Greten J, Abel M, Sido B, et al. Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease. Am J Pathol. 1995 Mar;146(3):688-94.
- Soulis T, Thallas V, Youssef S, Gilbert RE, McWilliam BG, Murray-McIntosh RP, Cooper ME. Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury. Diabetologia. 1997 Jun;40(6):619-28.
- Zhang F, Kent KC, Yamanouchi D, et al. Anti-receptor for advanced glycation end products therapies as novel treatment for abdominal aortic aneurysm. Ann Surg 2009;250(3):416–23.
- Nowak A, Przywara-Chowaniec B, Damasiewicz-Bodzek A, Blachut D, Nowalany-Kozielska E, Tyrpień Golder K. Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE). Cells. 2021 Dec 13;10(12):3523.
- Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, et al. Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease. Neurobiol Aging 2011;32: 763-77.
- Donato R. S100: a multigenic family of calcium-modulated proteins of the EFhand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 2001;33: 637-68.
- Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W,Sunderkotter C, et al. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticularonset juvenile rheumatoid arthritis. Arthritis Rheum 2000;43: 628-37.
- Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004;50: 3762-71.
- Soyfoo MS, Roth J, Vogl T, Pochet R, Decaux G. Phagocyte-specific S100A8/A9 protein levels during disease exacerbations and infections in systemic lupus erythematosus. J Rheumatol 2009;36: 2190-4.
- Tam XHL, Shiu SWM, Leng L, Bucala R, Betteridge DJ, Tan KCB. Enhanced expression of receptor for advanced glycation endproducts is associated with low circulating soluble isoforms of the receptor in Type 2 diabetes. Clin Sci (Lond) 2011;120(2):81–89.
- Hammady MMR, Khashali SEL, Halim HA, Rashed L, Hussein M. Soluble receptor for advanced glycation end products (sRAGE) innon-diabetic hemodialysis patients and chronic kidney disease. Med J Cairo Univ 2012;80: 69–75.
- Stewart C, Cha S, Caudle RM, Berg K, Katz J. Decreased levels of soluble receptor for advanced glycation end products in patients with primary Sjogren's syndrome. Rheumatol Int 2008;28: 771-6.
- Islam S, Mir AR, Abidi M, Talha M, Zafar A, Habib S, et al. Methylglyoxal modified IgG generates autoimmune response in rheumatoid arthritis. Int J Biol Macromol. 2018 Oct 15;118(Pt A):15-23.
- Sirois CM, Jin T, Miller AL, Bertheloot D, Nakamura H, Horvath GL, et al. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA. J Exp Med. 2013 Oct 21;210(11):2447-63.
- Hofmann MA, Drury S, Hudson BI, Gleason MR, Qu W,Lu Y, et al. RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun 2002;3: 123-35.
- Abdulahad DA, Westra J, Bijzet J, Limburg PC, Kallenberg CG, Bijl M. High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus. Arthritis Res Ther 2011;13:R71.
- Li J, Xie H, Wen T, Liu H, Zhu W, Chen X. Expression of high mobility group box chromosomal protein 1 and its modulating effects on downstream cytokines in systemic lupus erythematosus. J Rheumatol 2010;37: 766–75.
- Ma CY, Jiao YL, Zhang J et al. Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN‐alpha and TNF‐alpha in systemic lupus erythematosus. Rheumatol Int 2012;32: 395–402.
- Nienhuis HL, de Leeuw K, Bijzet J et al. Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts. Rheumatology (Oxford) 2008;47: 1554–8.
- Tan KC, Shiu SW, Chow WS, Leng L, Bucala R, Betteridge DJ. Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes. Diabetologia 2006;49: 2756–62.
- Kalousová M, Hodková M, Kazderová M, Fialová J, Tesar V, Dusilová-Sulková S, Zima T. Soluble receptor for advanced glycation end products in patients with decreased renal function. Am J Kidney Dis. 2006 Mar;47(3):406-11.
- Forbes JM, Thorpe SR, Thallas Bonke V et al. Modulation of soluble receptor for advanced glycation end products by angiotensin‐converting enzyme‐1 inhibition in diabetic nephropathy. J Am Soc Nephrol 2005;16: 2363–72.
- Chavakis T, Bierhaus A, Al Fakhri N et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 2003;198:1507–15.