Sjögren Sendromlu ve Diabetik Hastalarda Serum Büyüme Faktörleri ve İnflamatuar Sitokin Düzeyleri

Year 2023, , 360 - 366, 31.08.2023

Şule Nur Acar Duyan , Banu Bozkurt , Ali Unlu , Sema Yilmaz , Yalçın Karaküçük

https://doi.org/10.54005/geneltip.1314282

Cited By: 1

Abstract

ÖZ
Amaç: Sjögren sendromu (SS) ve diabetes mellitus (DM) kuru göz hastalığının yaygın nedenleridir ve yapay gözyaşı preperatları yeterli olmadığında otolog serum kullanılmaktadır. Amacımız SS ve DM hastalarının serum büyüme faktörü ve inflamatuar sitokin düzeylerini sağlıklı bireylerle karşılaştırmaktı.
Gereç ve Yöntem: Çalışmaya 23 SS hastası (ortalama yaş 52,70±7,55), 25 DM hastası (ortalama yaş 56,68±6,53) ve 23 sağlıklı birey (ortalama yaş 51,70±9,14) alındı. Ayrıntılı oftalmolojik muayene sonrasında Schirmer testi, gözyaşı kırılma zamanı (GKZ) ve Ocular Surface Disease Index (OSDI) skorları ölçüldü. Altı farklı proinflamatuar interlökin (IL), beş büyüme faktörü, matriks metaloproteinaz-9 ve fibronektinin serum seviyeleri, immünoassay ile ölçüldü. Karşılaştırma için tek yönlü ANOVA veya Kruskal-Wallis testleri ve Dunn-Bonferroni post hoc analizi kullanıldı ve p<0,05 anlamlı kabul edildi.
Bulgular: Schirmer testi ve GKZ, SS grubunda (2,08±1,72 mm/5 dk ve 3,08±2,08 sn), DR (10,24±4,63 mm/5 dk ve 4,20±3,09 sn) ve kontrol grubuna (13.30±5.95 mm/5 dk ve 9.00±1.75 sn) göre anlamlı olarak düşüktü (p<0,001). İncelenen parametrelerden ortalama serum IL-23 düzeyi SS grubunda (156,66±207,94 pg/mL), DM ve kontrol gruplarına göre (sırasıyla 73,48±95,91 ve 69,59±105,39 pg/mL) anlamlı olarak yüksekti (p< 0.05). Serum insülin benzeri büyüme faktörü 1 (IGF-1) düzeyi DM'li hastalarda en düşüktü (DM: 12,89±21,09, SS: 30,77±19,85 ve kontrol: 27,08±21,93 ng/mL) (p<0,05). Sjögren sendromu hastalık aktivite indeksi (ESSDAI) GKZ ile negatif, IL-1, IL-2 ve fibronektin ile pozitif korelasyon gösterdi (p<0.005).
Sonuç: IL-23 ve IGF-1 dışında SS ve DM'li hastalardan elde edilen serum içerikleri sağlıklı bireylerle benzerdir. Bu nedenle, otolog serum, bu kişilerde eksik olan gözyaşını yerine koymak için iyi bir seçenek gibi görünmektedir.

Keywords

İnflamatuar sitokinler, Büyüme Faktörleri, Sjögren sendromu, Diabetes mellitus, Otolog serum

Serum Inflammatory Cytokines and Growth Factors in Patients with Sjögren’s Syndrome and Diabetes Mellitus

Abstract

Abstract
Background/ Aims: Sjögren’s syndrome (SS) and diabetes mellitus (DM) are common causes of dry eye disease (DED) and autologous serum is used when artificial tears are not sufficient. Our aim was to compare serum growth factor and inflammatory cytokine levels of SS and DM patients with the healthy individuals.
Methods: Twenty-three SS patients (mean age 52.70±7.55 years), 25 DM patients (mean age 56.68±6.53 years), and 23 healthy subjects (mean age 51.70±9.14 years) were included in the study. After detailed ophthalmological examination, Schirmer test, tear break-up time (TBUT) and Ocular Surface Disease Index (OSDI) scores were measured. Serum levels of six different proinflammatory interleukins (IL), five growth factors, matrix metalloproteinase-9, and fibronectin were measured by immunoassay. One-way ANOVA or Kruskal-Wallis tests and Dunn-Bonferroni post hoc analysis were used for comparison and p<0.05 was considered significant.
Results: Schirmer test and TBUT were significantly lower in the SS group (2.08±1.72 mm/5 min and 3.08±2.08 s) than in the DR (10.24±4.63 mm/5 min and 4.20±3.09 s) and control groups (13.30±5.95 mm/5 min and 9.00±1.75 s) (p<0.001). Among the parameters studied, mean serum IL-23 level was significantly higher in the SS group (156.66±207.94 pg/mL) than in the DM and control groups (73.48±95.91 and 69.59±105.39 pg/mL, respectively) (p<0.05). Serum insulin-like growth factor 1 (IGF-1) level was lowest in DM patients (DM: 12.89±21.09, SS: 30.77±19.85, and control: 27.08±21.93 ng/mL) (p<0.05). Sjögren’s syndrome disease activity index (ESSDAI) showed a negative correlation with TBUT and a positive correlation with IL-1, IL-2 and fibronectin (p<0.005).
Conclusions: Except IL-23 and IGF-1, the contents of serum obtained from patients with SS and DM are similar with the healthy individuals. Therefore, autologous serum seems to be a good option to replace deficient tear fluid in these subjects.

Keywords

Inflammatory cytokines, Growth factors, Sjögren’s syndrome, Diabetic mellitus, Autologous serum

References

• Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, et al. TFOS DEWS II epidemiology report. The ocular surface. 2017;15:334-365.
• Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, et al. TFOS DEWS II definition and classification report. The ocular surface. 2017;15:276-283.
• Huang R, Su C, Fang L, Lu J, Chen J, Ding Y. et al. Dry eye syndrome: comprehensive etiologies and recent clinical trials. International Ophthalmology. 2022:1-20.
• Coursey TG, de Paiva CS. Managing Sjögren’s Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy. Clinical ophthalmology (Auckland, NZ). 2014;8:1447.
• Zhang M, Kim E, Akpek EK. Prevalence and predictors of Sjögren's syndrome in a prospective cohort of patients with aqueous-deficient dry eye. British journal of ophthalmology. 2012;96:1498-1503.
• Kang YS, Lee HS, Li Y, Choi W, Yoon KC et al. Manifestation of meibomian gland dysfunction in patients with Sjögren’s syndrome, non-Sjögren’s dry eye, and non-dry eye controls. International ophthalmology. 2018;38:1161-1167.
• Najafi L, Malek M, Valojerdi AE, Aghili R, Khamseh ME, Fallah AE, et al. Dry eye and its correlation to diabetes microvascular complications in people with type 2 diabetes mellitus. Journal of Diabetes and its Complications. 2013;27:459-462.
• Manaviat MR, Rashidi M, Afkhami-Ardekani M, Shoja MR. Prevalence of dry eye syndrome and diabetic retinopathy in type 2 diabetic patients. BMC ophthalmology. 2008;8:1-5.
• Achtsidis V, Eleftheriadou I, Kozanidou E, Voumvourakis KI, Stamboulis E, Theodosiadis PG et al. Dry eye syndrome in subjects with diabetes and association with neuropathy. Diabetes care. 2014;37:e210-e211.
• Zou X, Lu L, Xu Y, Zhu J, He J, Zhang B, et al. Prevalence and clinical characteristics of dry eye disease in community-based type 2 diabetic patients: the Beixinjing eye study. BMC ophthalmology. 2018;18:1-7.
• Nadeem H, Malik TG, Mazhar A, Ali A. Association of Dry Eye Disease with Diabetic Retinopathy. AGE. 2020;45:49-77.
• Roth M, Dierse S, Alder J, Holtmann C, Geerling G. Incidence, prevalence, and outcome of moderate to severe neurotrophic keratopathy in a German tertiary referral center from 2013 to 2017. Graefe's Archive for Clinical and Experimental Ophthalmology. 2022;260:1961-1973.
• Dua HS, Said DG, Messmer EM, Rolando M, Benitez-del-Castillo JM, Hossain PN, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107-131.
• Dogru M, Tsubota K. Pharmacotherapy of dry eye. Expert opinion on pharmacotherapy. 2011;12:325-334.
• Quinto GG, Campos M, Behrens A. Autologous serum for ocular surface diseases. Arquivos brasileiros de oftalmologia. 2008;71:47-54.
• Jones L, Downie LE, Korb D, Benitez-del-Castillo JM, Dana R, Deng SX, et al. TFOS DEWS II management and therapy report. The ocular surface. 2017;15:575-628.
• Ralph RA, Doane MG, Dohlman CH. Clinical experience with a mobile ocular perfusion pump. Archives of Ophthalmology. 1975;93:1039-1043.
• Giannaccare G, Versura P, Buzzi M, Primavera L, Pellegrini M, Campos EC. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfusion and Apheresis Science. 2017;56:595-604.
• Ali TK, Gibbons A, Cartes C, Zarei-Ghanavati S, Gomaa M, Gonzalez I, et al. Use of autologous serum tears for the treatment of ocular surface disease from patients with systemic autoimmune diseases. American journal of ophthalmology. 2018;189:65-70.
• Liu L, Hartwig D, Harloff S, Herminghaus P, Wedel T, Geerling G. An optimised protocol for the production of autologous serum eyedrops. Graefe's Archive for Clinical and Experimental Ophthalmology. 2005;243:706-714.
• Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis & Rheumatism. 1984;27:459-461.
• Anitua E, Muruzabal F, Tayebba A, Riestra A, Perez VL, Merayo‐Lloves J, et al. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta ophthalmologica. 2015;93:e605-e614.
• Tsubota K, Goto E, Shimmura S, Shimazaki J. Treatment of persistent corneal epithelial defect by autologous serum application. Ophthalmology. 1999;106:1984-1989.
• Freire V, Andollo N, Etxebarria J, Hernáez-Moya, R, Durán JA, Morales MC. Corneal wound healing promoted by 3 blood derivatives: an in vitro and in vivo comparative study. Cornea. 2014;33:614-620.
• López-García JS, García-Lozano I, Rivas L, Giménez C, Acera A, Suárez-Cortés T. Effects of autologous serum eye drops on conjunctival expression of MUC5AC in patients with ocular surface disorders. Cornea. 2016;35:336-341.
• Jirsova K, Brejchova K, Krabcova I, Filipec M, Al Fakih A, Palos M, et al. The application of autologous serum eye drops in severe dry eye patients; subjective and objective parameters before and after treatment. Current Eye Research. 2014;39:21-30.
• Tsubota K, Goto E, Fujita H, Goto E, Shimmura S. New treatment of dry eye by autologous serum application in Sjögren’s syndrome. British Journal of Ophthalmology. 1999;83:390-395.
• Ma I-H, Chen LW, Tu W-H, Lu CJ, Huang CJ, Chen WL. Serum components and clinical efficacies of autologous serum eye drops in dry eye patients with active and inactive Sjogren syndrome. Taiwan Journal of Ophthalmology. 2017;7:213.
• Hwang J, Chung S-H, Jeon S, Kwok SK, Park SH, Kim MS. Comparison of clinical efficacies of autologous serum eye drops in patients with primary and secondary Sjögren syndrome. Cornea. 2014;33:663-667.
• Quevedo-Martínez JU, Garfias Y, Jimenez J, Garcia O, Venegas D, de Lucio VMB. Pro-inflammatory cytokine profile is present in the serum of Mexican patients with different stages of diabetic retinopathy secondary to type 2 diabetes. BMJ Open Ophthalmology. 2021;6:e000717.
• Mansoor G, Tahir M, Maqbool T, Abbasi SQ, Hadi F, Shakoori TA, et al. Increased Expression of Circulating Stress Markers, Inflammatory Cytokines and Decreased Antioxidant Level in Diabetic Nephropathy. Medicina. 2022;58:1604.
• Vitali C, Bombardieri S, Jonsson R. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554-558.
• Seror R, Bootsma H, Saraux A, Bowman SJ, Theander E, Brun JG, et al. Defining disease activity states and clinically meaningful improvement in primary Sjögren's syndrome with EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Annals of the rheumatic diseases. 2016;75:382-389.
• Mounirou BA, Adam ND, Yakoura AK, Aminou MS, Liu YT, Tan LY. Diabetic Retinopathy: An Overview of Treatments. Indian Journal of Endocrinology and Metabolism. 2022;26:111.
• Wolffsohn JS, Arita R, Chalmers R, Djalilian A, Dogru M, Dumbleton K, Djalilian A, Dogru M, Dumbleton K, et al. TFOS DEWS II diagnostic methodology report. The ocular surface. 2017;15(3):539-74.
• Higuchi A. Autologous serum and serum components. Investigative Ophthalmology & Visual Science. 2018;59:DES121-DES129.
• Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM. Systemic and local interleukin-17 and linked cytokines associated with Sjögren’s syndrome immunopathogenesis. The American journal of pathology. 2009;175:1167-1177.
• López‐Villalobos EF, Muñoz‐Valle JF, Palafox‐Sánchez CA, Pillemer S, Wahl SM. Cytokine profiles and clinical characteristics in primary Sjögren´ s syndrome patient groups. Journal of clinical laboratory analysis. 2021;35:e23629.
• Koleva-Georgieva DN, Sivkova NP, Terzieva D. Serum inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF have influence on the development of diabetic retinopathy. Folia Med (Plovdiv). 2011;53:44-50.
• Hernández-Da Mota SE, Soto-Bahena JJ, Viveros-Sandoval ME, Cardiel-Ríos M. Pro-inflammatory serum cytokines in diabetic retinopathy. Cirugía y Cirujanos (English Edition). 2015;83:100-106.
• Chen H, Wen F, Zhang X, Su SB. Expression of T-helper-associated cytokines in patients with type 2 diabetes mellitus with retinopathy. Molecular vision. 2012;18:219.
• Ozturk BT, Bozkurt B, Kerimoglu H, Okka M, Kamis U, Gunduz K. Effect of serum cytokines and VEGF levels on diabetic retinopathy and macular thickness. Molecular vision. 2009;15:1906.
• Patel R, Zhu M, Robertson DM. Shifting the IGF-axis: An age-related decline in human tear IGF-1 correlates with clinical signs of dry eye. Growth Hormone & IGF Research. 2018;40:69-73.
• Teppala S, Shankar A. Association between serum IGF-1 and diabetes among US adults. Diabetes care. 2010;33:2257-2259.
• Khan N, Paterson AD, Roshandel D, Raza A, Ajmal M, Waheed NK, et al. Association of IGF1 and VEGFA polymorphisms with diabetic retinopathy in Pakistani population. Acta Diabetologica. 2020;57:237-245.
• Feldmann B, Lang GE, Arnavaz A, Jehle PM, Böhm BO, Lang GK. Diminished serum levels of free IGF-I in patients with diabetic retinopathy. Der Ophthalmologe. 1999;96:300-305.
• Markoulli M, Flanagan J, Tummanapalli SS, Wu J, Willcox M. The impact of diabetes on corneal nerve morphology and ocular surface integrity. Ocul Surf. 2018;16:45-57.
• Nagano T, Nakamura M, Nakata K, Yamaguchi T, Takase K, Okahara A, et al. Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy. Investigative ophthalmology & visual science. 2003;44:3810-3815.
• Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for corneal neurotrophic ulcers. New England Journal of Medicine. 1998;338:1174-1180.
• Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. 2000;107:1347-1351.
• Roszkowska AM, Inferrera L, Aragona E, Gargano R, Postorino EI, Aragona P. Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin). Eur J Ophthalmol. 2022;32:3402-3410.
• Anfimova ML, Lebedeva TV, Khodarev NV, Vassiliev VI, Nassonova VA. Fibronectin, Cryoglobulinemia and Immune Complexes in Sjogren's Syndrome Patients. Russ J Immunol. 1996;1:29-34.
• Silvestre FJ, Puente A, Bagán JV, Castell JV. Presence of fibronectin peptides in saliva of patients with Sjögren’s syndrome: a potential indicator of salivary gland destruction. Med Oral Patol Oral Cir Bucal. 2009;14:e365-370.
• Seghieri G, Bartolomei G, De Giorgio L. Plasma fibronectin in diabetic retinopathy and macroangiopathy. Diabete & Metabolisme. 1986;12:186-190.
• Lee IK, Park KY, Oh HK, Park RW, Jo JS. Plasma type IV collagen and fibronectin concentrations in diabetic patients with microangiopathy. Journal of Korean Medical Science. 1994;9:341-346.
• De Giorgio LA, Seghieri G, Gironi A, Mammini P, Bartoli U, Bartolomei G. Raised plasma fibronectin concentration is related to the presence of diabetic retinopathy. Acta diabetologia latina. 1984;21:251-256.