Abstract
Amaç: Sarkoidoz, vücuttaki bütün organları etkileyebilen, kazeifiye olmayan granülomların varlığı ile karakterize, nedeni bilinmeyen sistemik inflamatuar bir hastalıktır. Bazı çalışmalar peptitler ve sarkoidoz arasında bir ilişki olduğunu önermektedir. Bu çalışmanın amacı sarkoidozda serum hemokinin-1 (HK-1) ve adropin düzeylerinin tanısal değerlerini araştırmak ve hastalıkta rolünü değerlendirmektir.
Hastalar ve Metod: Çalışma Nisan 2021-Şubat 2022 tarihleri arasında bir üniversite hastanesinde gerçekleştirildi. Çalışmaya sarkoidoz tanılı 38 hasta (14 erkek, 24 kadın) ve 38 sağlıklı (14 erkek, 24 kadın) birey alındı. Hastaların demografik özellikleri, yaşı, cinsiyeti, hastalık süresi ve akciğer dışı tutulumu kaydedildi. HK-1 ve adropin düzeyleri, sandviç ELISA (enzyme linked immunosorbent assay) yöntemi ile belirlendi.
Bulgular: Sarkoidozlu hastalarda HK-1 seviyesi sağlıklı bireylere göre daha yüksekti, aradaki fark istatistiksel olarak anlamlıydı (0,67±0,23 ve 0,54±0,24 ng/ml, p=0,012). Serum adropin düzeyleri sarkoidoz hasta grubunda 207,84±246,72 ng/L, sağlıklı kontrol grubunda 151,16±171,76 ng/L olarak belirlendi. Sarkoidozlu hastalarının adropin seviyeleri ise sağlıklı bireylere göre anlamlı fark belirlenmedi (p=0,076). Serum adropin seviyeleri, BAL CD4+ seviyeleri ile negatif (r=-,880 ve p=0.002) ve BAL CD8+ seviyeleri ile pozitif korrelasyon gösterdi (r=,697 ve p=0.037).
Sonuç: Çalışmada sarkoidozlu hastaların sağlıklı kontrollere göre anlamlı olarak daha yüksek HK-1 seviyeleri gösterdiği ve HK-1'in bu hastalık için invaziv olmayan yararlı bir tanısal biyobelirteç olabileceği belirlendi. Literatürde henüz sarkoidozda serum HK-1 ve adropin düzeyleri henüz araştırılmamıştır. Bu konuyu açıklığa kavuşturmak için daha fazla ve geniş çaplı çalışmalara ihtiyaç vardır.
Keywords
Project Number
none
References
- Sève P, Pacheco Y, Durupt F, Jamilloux Y, Gerfaud-Valentin M, Isaac S, et al. Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis. Cells 2021;10(4):766. doi:10.3390/cells10040766.
- Baughman RP, Lower EE, Gibson K. Pulmonary manifestations of sarcoidosis. Presse Med 2012;41(6 Pt 2):e289-302. doi:10.1016/j.lpm.2012.03.019.
- Belperio JA, Shaikh F, Abtin F, Fishbein MC, Saggar R, Tsui E, et al. Extrapulmonary sarcoidosis with a focus on cardiac, nervous system, and ocular involvement. EClinicalMedicine 2021;37:100966. doi:10.1016/j.eclinm.2021.100966.
- Musellim B, Okumus G, Uzaslan E, Akgün M, Cetinkaya E, Turan O, et al., Turkish Interstitial Lung Diseases Group. Epidemiology and distribution of interstitial lung diseases in Turkey. Clin Respir J 2014;8(1):55-62. doi:10.1111/crj.12035.
- Govender P, Berman JS. The Diagnosis of Sarcoidosis. Clin Chest Med 2015;36(4):585-602. doi:10.1016/j.ccm.2015.08.003.
- Ziegenhagen MW, Benner UK, Zissel G, Zabel P, Schlaak M, Müller-Quernheim J. Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers. Am J Respir Crit Care Med 1997;156(5):1586-92. doi:10.1164/ajrccm.156.5.97-02050.
- Lavi H, Assayag M, Schwartz A, Arish N, Fridlender ZG, Berkman N. The association between osteopontin gene polymorphisms, osteopontin expression and sarcoidosis. PLoS One. 2017 Mar 2;12(3):e0171945. doi: 10.1371/journal.pone.0171945.
- Drent M, van den Berg R, Haenen GR, van den Berg H, Wouters EF, Bast A. NF-kappaB activation in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2001;18(1):50-6. PMID: 11354547.
- Ahmadzai H, Cameron B, Chui J, Lloyd A, Wakefield D, Thomas PS. Measurement of neopterin, TGF-β1 and ACE in the exhaled breath condensate of patients with sarcoidosis. J Breath Res;7(4):046003. doi:10.1088/1752-7155/7/4/046003.
- Onaga T. Tachykinin: recent developments and novel roles in health and disease. Biomol Concepts 2014;5(3):225-43. doi:10.1515/bmc-2014-0008.
- Morteau O, Lu B, Gerard C, Gerard NP. Hemokinin 1 is a full agonist at the substance P receptor. Nat Immunol. 2001;2(12):1088. doi: 10.1038/ni1201-1088.
- Ganjiwale A, Cowsik SM. Membrane-induced structure of novel human tachykinin hemokinin (hHK1). Biopolymers 2015;103(12): 702-10.
- Borbély É, Helyes Z. Role of hemokinin-1 in health and disease. Neuropeptides 2017;64:9-17.
- Grassin-Delyle S, Naline E, Buenestado A, Risse PA, Sage E, Advenier C, et al. Expression and function of human hemokinin-1 in human and guinea pig airways. Respir Res 2010;11(1):139. doi: 10.1186/1465-9921-11-139.
- Jasaszwili M, Billert M, Strowski MZ, Nowak KW, Skrzypski M. Adropin as A Fat-Burning Hormone with Multiple Functions- Review of a Decade of Research. Molecules 2020;25(3):549. doi:10.3390/molecules25030549.
- Yolbas S, Kara M, Kalayci M, Yildirim A, Gundogdu B, Aydin S, et al. ENHO gene expression and serum adropin level in rheumatoid arthritis and systemic lupus erythematosus. Adv Clin Exp Med 2018;27(12):1637-1641. doi:10.17219/acem/75944.
- Rybicki BA, Major M, Popovich J Jr, Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997;145(3):234-41. doi:10.1093/oxfordjournals.aje.a009096.
- Criado E, Sánchez M, Ramírez J, Arguis P, de Caralt TM, Perea RJ, et al. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics 2010;30(6):1567-86. doi:10.1148/rg.306105512.
- Oswald-Richter KA, Beachboard DC, Seeley EH, Abraham S, Shepherd BE, Jenkins CA, et al. Dual analysis for mycobacteria and propionibacteria in sarcoidosis BAL. J Clin Immunol 2012;32(5):1129-40. doi:10.1007/s10875-012-9700-5.
- Agostini C, Adami F, Semenzato G. New pathogenetic insights into the sarcoid granuloma. Curr Opin Rheumatol 2000;12(1):71-6. doi:10.1097/00002281-200001000-00012.
- Bennett D, Cameli P, Lanzarone N, Carobene L, Bianchi N, Fui A, et al. Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis. Respir Res 2020;21(1):6. doi:10.1186/s12931-019-1263-z.
- Date T, Shinozaki T, Yamakawa M, Taniguchi I, Suda A, Hara H, et al. Elevated plasma brain natriuretic peptide level in cardiac sarcoidosis patients with preserved ejection fraction. Cardiology 2007;107(4):277-80. doi:10.1159/000095518.
- Joos GF, Germonpré PR, Pauwels RA. Role of tachykinins in asthma. Allergy 2000;55(4):321-37. doi:10.1034/j.1398-9995.2000.00112.x.
- Noveral JP, Grunstein MM. Tachykinin regulation of airway smooth muscle cell proliferation. Am J Physiol 1995;269(3 Pt 1):L339-43. doi:10.1152/ajplung.1995.269.3.L339.
- Lotz M, Vaughan JH, Carson DA. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science. 1988;241(4870):1218-21. doi:10.1126/science.2457950.
- Zhang Y, Lu L, Furlonger C, Wu GE, Paige CJ. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat Immunol 2000;1(5):392-7. doi:10.1038/80826.
- Dinh QT, Klapp BF, Fischer A. Airway sensory nerve and tachykinins in asthma and COPD. Pneumologie 2006;60(2):80-85. doi:10.1055/s-2005-915587.
- Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 2008;8(6):468-81. doi: 10.1016/j.cmet.2008.10.011.
- Wang B, Xue Y, Shang F, Ni S, Liu X, Fan B, et al. Association of serum adropin with the presence of atrial fibrillation and atrial remodeling. J Clin Lab Anal 2019;33(2):e22672. doi:10.1002/jcla.22672.
- Wong CM, Wang Y, Lee JT, Huang Z, Wu D, Xu A, et al. Adropin is a brain membrane-bound protein regulating physical activity via the NB-3/Notch signaling pathway in mice. J Biol Chem 2014;289(37):25976-86. doi: 10.1074/jbc.M114.576058.
- Celik E, Yilmaz E, Celik O, Ulas M, Turkcuoglu I, Karaer A, et al. Maternal and fetal adropin levels in gestational diabetes mellitus. J Perinat Med 2013;41(4):375-80. doi:10.1515/jpm-2012-0227.
- Sayın O, Tokgöz Y, Arslan N. Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease. J Pediatr Endocrinol Metab 2014;27(5-6):479-84. doi:10.1515/jpem-2013-0296.
- Wu L, Fang J, Chen L, Zhao Z, Luo Y, Lin C, Fan L. Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients. Clin Chem Lab Med 2014;52(5):751-8. doi:10.1515/cclm-2013-0844.
- Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, et al. Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) 2012;20(7):1394-402. doi:10.1038/oby.2012.31.
Abstract
Aim: Sarcoidosis is a systemic inflammatory disease and characterized by the presence of non-caseating granulomas which may affect all organs in the body. Some studies suggest an association between peptides and sarcoidosis. The goal of the study was to investigate the biomarker values of serum hemokinin-1 (HK-1) and adropin levels in sarcoidosis and to assess their role in the disease course.
Patients and Methods: The study was carried out in a university hospital between April 2021 and February 2022. Thirty-eight patients with diagnosed sarcoidosis (14 men and 24 women) and 38 healthy (14 men and 24 women) individuals were enrolled in the study. Demographic characteristics, age, gender, disease duration, and extrapulmonary involvement of the patients were enrolled. HK-1 and adropin levels were measured via the sandwich ELISA (enzyme linked immunosorbent assay) method.
Results: HK-1 level was elevated in the sarcoidosis patients than in the healthy individuals, these differences were significant statistically (0.67±0.23 and 0.54±0.24 ng/ml, p=0.012). The serum levels of adropin were measured as 207.84±246.72 ng/L in the sarcoidosis patients group and 151.16±171.76 ng/L in the healthy individuals group. No significant differences were determined in terms of the adropin levels in the patient's group when compared to the healthy individuals group (p=0.076). Serum adropin were negatively correlated with BAL CD4+ levels (r=-,880 and p=0.002) and positively correlated with BAL CD8+ levels (r=,697 and p=0.037).
Conclusions: At the study, it is determined that patients with sarcoidosis show significantly higher HK-1 levels than healthy controls, and HK-1 may be a useful non-invasive diagnostic biomarker for this disease. From the literature, serum HK-1 and adropin levels have not been investigated in sarcoidosis, yet. To clarify this topic, further and larger size studies are needed.
Keywords
Supporting Institution
none
Project Number
none
References
- Sève P, Pacheco Y, Durupt F, Jamilloux Y, Gerfaud-Valentin M, Isaac S, et al. Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis. Cells 2021;10(4):766. doi:10.3390/cells10040766.
- Baughman RP, Lower EE, Gibson K. Pulmonary manifestations of sarcoidosis. Presse Med 2012;41(6 Pt 2):e289-302. doi:10.1016/j.lpm.2012.03.019.
- Belperio JA, Shaikh F, Abtin F, Fishbein MC, Saggar R, Tsui E, et al. Extrapulmonary sarcoidosis with a focus on cardiac, nervous system, and ocular involvement. EClinicalMedicine 2021;37:100966. doi:10.1016/j.eclinm.2021.100966.
- Musellim B, Okumus G, Uzaslan E, Akgün M, Cetinkaya E, Turan O, et al., Turkish Interstitial Lung Diseases Group. Epidemiology and distribution of interstitial lung diseases in Turkey. Clin Respir J 2014;8(1):55-62. doi:10.1111/crj.12035.
- Govender P, Berman JS. The Diagnosis of Sarcoidosis. Clin Chest Med 2015;36(4):585-602. doi:10.1016/j.ccm.2015.08.003.
- Ziegenhagen MW, Benner UK, Zissel G, Zabel P, Schlaak M, Müller-Quernheim J. Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers. Am J Respir Crit Care Med 1997;156(5):1586-92. doi:10.1164/ajrccm.156.5.97-02050.
- Lavi H, Assayag M, Schwartz A, Arish N, Fridlender ZG, Berkman N. The association between osteopontin gene polymorphisms, osteopontin expression and sarcoidosis. PLoS One. 2017 Mar 2;12(3):e0171945. doi: 10.1371/journal.pone.0171945.
- Drent M, van den Berg R, Haenen GR, van den Berg H, Wouters EF, Bast A. NF-kappaB activation in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2001;18(1):50-6. PMID: 11354547.
- Ahmadzai H, Cameron B, Chui J, Lloyd A, Wakefield D, Thomas PS. Measurement of neopterin, TGF-β1 and ACE in the exhaled breath condensate of patients with sarcoidosis. J Breath Res;7(4):046003. doi:10.1088/1752-7155/7/4/046003.
- Onaga T. Tachykinin: recent developments and novel roles in health and disease. Biomol Concepts 2014;5(3):225-43. doi:10.1515/bmc-2014-0008.
- Morteau O, Lu B, Gerard C, Gerard NP. Hemokinin 1 is a full agonist at the substance P receptor. Nat Immunol. 2001;2(12):1088. doi: 10.1038/ni1201-1088.
- Ganjiwale A, Cowsik SM. Membrane-induced structure of novel human tachykinin hemokinin (hHK1). Biopolymers 2015;103(12): 702-10.
- Borbély É, Helyes Z. Role of hemokinin-1 in health and disease. Neuropeptides 2017;64:9-17.
- Grassin-Delyle S, Naline E, Buenestado A, Risse PA, Sage E, Advenier C, et al. Expression and function of human hemokinin-1 in human and guinea pig airways. Respir Res 2010;11(1):139. doi: 10.1186/1465-9921-11-139.
- Jasaszwili M, Billert M, Strowski MZ, Nowak KW, Skrzypski M. Adropin as A Fat-Burning Hormone with Multiple Functions- Review of a Decade of Research. Molecules 2020;25(3):549. doi:10.3390/molecules25030549.
- Yolbas S, Kara M, Kalayci M, Yildirim A, Gundogdu B, Aydin S, et al. ENHO gene expression and serum adropin level in rheumatoid arthritis and systemic lupus erythematosus. Adv Clin Exp Med 2018;27(12):1637-1641. doi:10.17219/acem/75944.
- Rybicki BA, Major M, Popovich J Jr, Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997;145(3):234-41. doi:10.1093/oxfordjournals.aje.a009096.
- Criado E, Sánchez M, Ramírez J, Arguis P, de Caralt TM, Perea RJ, et al. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics 2010;30(6):1567-86. doi:10.1148/rg.306105512.
- Oswald-Richter KA, Beachboard DC, Seeley EH, Abraham S, Shepherd BE, Jenkins CA, et al. Dual analysis for mycobacteria and propionibacteria in sarcoidosis BAL. J Clin Immunol 2012;32(5):1129-40. doi:10.1007/s10875-012-9700-5.
- Agostini C, Adami F, Semenzato G. New pathogenetic insights into the sarcoid granuloma. Curr Opin Rheumatol 2000;12(1):71-6. doi:10.1097/00002281-200001000-00012.
- Bennett D, Cameli P, Lanzarone N, Carobene L, Bianchi N, Fui A, et al. Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis. Respir Res 2020;21(1):6. doi:10.1186/s12931-019-1263-z.
- Date T, Shinozaki T, Yamakawa M, Taniguchi I, Suda A, Hara H, et al. Elevated plasma brain natriuretic peptide level in cardiac sarcoidosis patients with preserved ejection fraction. Cardiology 2007;107(4):277-80. doi:10.1159/000095518.
- Joos GF, Germonpré PR, Pauwels RA. Role of tachykinins in asthma. Allergy 2000;55(4):321-37. doi:10.1034/j.1398-9995.2000.00112.x.
- Noveral JP, Grunstein MM. Tachykinin regulation of airway smooth muscle cell proliferation. Am J Physiol 1995;269(3 Pt 1):L339-43. doi:10.1152/ajplung.1995.269.3.L339.
- Lotz M, Vaughan JH, Carson DA. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science. 1988;241(4870):1218-21. doi:10.1126/science.2457950.
- Zhang Y, Lu L, Furlonger C, Wu GE, Paige CJ. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat Immunol 2000;1(5):392-7. doi:10.1038/80826.
- Dinh QT, Klapp BF, Fischer A. Airway sensory nerve and tachykinins in asthma and COPD. Pneumologie 2006;60(2):80-85. doi:10.1055/s-2005-915587.
- Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 2008;8(6):468-81. doi: 10.1016/j.cmet.2008.10.011.
- Wang B, Xue Y, Shang F, Ni S, Liu X, Fan B, et al. Association of serum adropin with the presence of atrial fibrillation and atrial remodeling. J Clin Lab Anal 2019;33(2):e22672. doi:10.1002/jcla.22672.
- Wong CM, Wang Y, Lee JT, Huang Z, Wu D, Xu A, et al. Adropin is a brain membrane-bound protein regulating physical activity via the NB-3/Notch signaling pathway in mice. J Biol Chem 2014;289(37):25976-86. doi: 10.1074/jbc.M114.576058.
- Celik E, Yilmaz E, Celik O, Ulas M, Turkcuoglu I, Karaer A, et al. Maternal and fetal adropin levels in gestational diabetes mellitus. J Perinat Med 2013;41(4):375-80. doi:10.1515/jpm-2012-0227.
- Sayın O, Tokgöz Y, Arslan N. Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease. J Pediatr Endocrinol Metab 2014;27(5-6):479-84. doi:10.1515/jpem-2013-0296.
- Wu L, Fang J, Chen L, Zhao Z, Luo Y, Lin C, Fan L. Low serum adropin is associated with coronary atherosclerosis in type 2 diabetic and non-diabetic patients. Clin Chem Lab Med 2014;52(5):751-8. doi:10.1515/cclm-2013-0844.
- Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, et al. Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) 2012;20(7):1394-402. doi:10.1038/oby.2012.31.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Original Article |
| Authors | |
| Project Number | none |
| Early Pub Date | August 29, 2023 |
| Publication Date | August 31, 2023 |
| Submission Date | May 25, 2023 |
| Published in Issue | Year 2023 Volume: 33 Issue: 4 |
Journal of General Medicine is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY NC).