Thiol/disulfide homeostasis in patients with primary Sjögren’s syndrome

Thiol/disulfide homeostasis in pSS

  • Nuray YILMAZ CAKMAK MD; Ankara City Hospital, Department of Internal Medicine, Ankara, Turkey
  • Salih BASER Yıldırım Beyazıt University Ankara City Hospital, Department of Internal Medicine
  • Sükran ERTEN MD, Prof; Yıldırım Beyazıt University, Ankara City Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey
  • Emin GEMCIOGLU MD; Ankara City Hospital, Department of Internal Medicine, Ankara, Turkey
  • Ozcan EREL MD, Prof; Yıldırım Beyazıt University, Ankara City Hospital, Department of Medical Biochemistry Ankara, Turkey
Keywords: Primary Sjögren's syndrome, Oxidative stress, Thiol/disulfide homeostasis




Primary Sjögren’s syndrome (pSS) is a disease associated with the overexpression of proinflammatory cytokines, and oxidative stress is one of the factors responsible for its etiopathogenesis. This study aimed to investigate the thiol/disulfide homeostasis in pSS patients.

Materials and Methods

The study included 68 pSS patients and 69 healthy controls. Thiol/disulfide homeostasis (total thiol, native thiol, and disulfide levels) was measured using the automatic spectrophotometric method developed by Erel and Neselioglu, and the results of the 2 groups were compared.


The gender and age distributions of the pSS and control groups were similar (P = 1.000 and P = 0.065). Total thiol and native thiol levels were lower in the pSS group than in the control group (470.08 ± 33.65 µmol/L vs. 528.21 ± 44.99 µmol/L, P < 0.001, and 439.14 ± 30.67 µmol/L vs. 497.56 ± 46.70 µmol/L, P < 0.001, respectively). There were no differences in disulfide levels  between groups [17.00 (range0.70–217.0) µmol/L vs. 14.95 (range 2.10–40.10) µmol/L, P = 0.195].


It was concluded that the thiol/disulfide balance shifted towards disulfide in patients with pSS.


1- Ramos-Casals M, Tzioufas AG, Font J. Primary Sjögren's syndrome: new clinical and therapeutic concepts. Ann Rheum Dis 2005; 64:347.
2- Pertovaara M, Korpela M, Uusitalo H, et al. Clinical follow up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or both). Ann Rheum Dis 1999; 58:423.
3- Bikker A, van Woerkom JM, Kruize AA, Wenting-van Wijk M, de Jager W, Bijlsma JW, et al.Increased expression of interleukin-7 in labial salivary glands of patients with primary Sjögren ’s syndrome correlates with increased infl ammation. Arthritis Rheum 2010; 62: 969 – 977.
4- Sözmen E. Radikal Kavramı ve Oksijen Radikalleri. İçinde: Onat T, Emerk K, Sözmen EY (Editörler). İnsan Biyokimyası, Palme Yayıncılık, 2002: p. 666-673
5- Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes, Free Radical Biology and Medicine, 2013, 65: 244-253.
6- Cremers CM, Jakob U. Oxidant sensing by reversible disulfide bond formation, Journal of Biological Chemistry, 2013,288(37):26489-26496
7- Schwartz HL, Oppenheimer JH. Ontogenesis of 3, 5, 3′-triiodothyronine receptors in neonatal rat brain: dissociation between receptor concentration and stimulation of oxygen consumption by 3, 5, 3′-triiodothyronine, Endocrinology, 1978, 103(3): 943-948
8- Nkabyo YS, Ziegler TR, Gu LH, Watson WH, Jones DP. Glutathione and thioredoxin redox during differentiation in human colon epithelial (Caco-2) cells, American Journal of Physiology-Gastrointestinal and Liver Physiology, 2002, 283(6): G1352-G1359.
9- Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X; International Sjögren's Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 2017 Jan;69(1):35-45
10- Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis, Clinical Biochemistry, 2014, 47(18): 326-332.
11- Ramos-Casals M, Font J. Primary Sjögren's syndrome: current and emergent aetiopathogenic concepts. Rheumatology(Oxford) 2005;44(11):1354-67
12- Chisholm DM, Mason DK. Labial salivary gland biopsy in Sjögren's disease. J Clin Pathol 1968; 21 (5): 656-60
13- Kurimoto C, Kawano S, Tsuji G, Hatachi S, Jikimoto T, Sugiyama D, et al. Thioredoxin may exert a protective eff ect against tissue damage caused by oxidative stress in salivary glands of patients with Sjögren’ s syndrome. J Rheumatol ,2007; 34: 2035 – 2043
14- Cejkov á J, Ardan T, Simonov á Z, Cejka C, Malec J, Dotrelov á D, et al. Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sjögren’s syndrome) and its possible contribution to the development of ocular surface oxidative injuries. Histol Histopathol 2008; 23: 1477 – 1483.
15- Norheim KB, Jonsson G, Harboe E, Hanasand M, Göransson L, Omdal R. Oxidative stress, as measured by protein oxidation, is increased in primary Sjögren’s syndrome. Free Radic Res 2012; 46: 141 – 146.
16- Ryo K, Yamada H, Nakagawa Y, Tai Y, Obara K, Inoue H, et al. Possible involvement of oxidative stress in salivary gland of patients with Sjogren’ s syndrome. Pathobiology 2006; 73: 252 – 260.
17- Içme F, Erel Ö, Avcı A, Satar S, Gülen M, Acehan S. The relation between oxidative stress parameters, ischemic stroke, and hemorrhagic stroke. Turk J Med Sci. 2015;45(4):947-53.
18- Nagy P. Kinetics and mechanisms of thiol-disulfide exchange covering direct substitution and thiol oxidation-mediated pathways. Antioxid Redox Signal. 2013;18(13):1623-41.
19-Karatas G, Gunduz R, Haskul I, Ustun B, Neselioglu S, Karatas F, Akyuz M, Erel O. Dynamic thiol and disulphide homoeostasis in fibromyalgia. Arch Med Sci 2019;16(3): 597-602
20- Tuzcu A, Aydoğan R, Omma A,et al. Thiol/disülfite homeostasis in partient with rheumatoid arthritis ROM.J.intern med.,2018, 0, 0, 1-18
21- Clemens DL, Duryee MJ, Hall JH, Thiele GM, Mikuls TR, Klassen LW, Zimmerman MC, Anderson DR. Relevance of the antioxidant properties of methotrexate and doxycycline to their treatment of cardiovascular disease. Pharmacol Ther. 2019 Oct 15:107413.
Original paper