Evaluation of thiol/disulfide hemostasis and serum Ischemia modified albumin as oxidative stress biomarkers in systemic lupus erythematosus patients: Relationship with major organ involvement and disease activity
Restricted accessResearch articleFirst published online October, 2022
Evaluation of thiol/disulfide hemostasis and serum Ischemia modified albumin as oxidative stress biomarkers in systemic lupus erythematosus patients: Relationship with major organ involvement and disease activity
We aimed to compare thiol/disulfide hemostasis and serum ischemia-modified albumin (IMA) levels, which are indicators of oxidative stress (OS), in patients with systemic lupus erythematosus (SLE), with the healthy control (HC) group and to evaluate the relationship of these parameters with disease activity and major organ involvement.
Material-Methods
Eighty-four SLE patients and 96 HCs were included in this study. The disease activity of SLE patients was calculated using The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Patients with SLEDAI-2K ≤ 5 were classified as low disease activity (LDA) and those with SLEDAI-2K > 6 as high disease activity (HDA). Thiol/disulfide hemostasis was evaluated using a new automated method and natural thiol (NT), total thiol (TT), disulfide (SS) levels, SS/NT, SS/TT, NT/TT ratios, and serum IMA levels were recorded.
Results
NT and TT levels were significantly lower (490.11 ± 123.61 vs 536.96 ± 86.05, p = 0.003) (532.56 ± 125.80 vs 565.72 ± 89.82, p = 0.046), SS level (21.22 ± 11.75 vs 13.37 ± 9.31, p < 0.001) was higher, and SS/TT (4.64 ± 2.93 vs 2.52 ± 1.82, p < 0.001) and SS/NT (4.12 ± 2.33 vs 2.35 ± 1.59, p < 0.001) ratios were significantly higher in SLE patients compared to HCs. IMA values were not different between the two groups (p = 0.920). NT (449.84 ± 136.98 vs 520.32 ± 104.11, p = 0.012) and TT levels (492.01 ± 138.45±562.97 ± 107.09, p = 0.013) were significantly lower and serum IMA levels (0.802 ± 0.089 vs 0.764 ± 0.040, p = 0.023) were significantly higher in SLE patients with HDA than in LDA patients. There was a weak negative correlation between NT (r = −0.284, p=0.009) (r = −0.291, p = 0.007) and TT levels (r = −0.281, p = 0.010) (r = −0.289, p = 0.008) and a weak positive correlation between IMA levels (r = 0.279, p = 0.011) (r = 0.263, p = 0.016) and SLEDAI-2K, and major organ involvement.
Conclusion
It is thought that thiol/disulfide hemostasis and IMA levels may be used as ideal biomarkers of OS in SLE patients and may reflect the disease activity and major organ involvement.
ShahDMahajanNSahS, et al.Oxidative stress and its biomarkers in systemic lupus erythematosus. J Biomed Sci2014; 21(123).
2.
AvalosIChungCPOeserA, et al.Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms. Lupus2007; 16(3): 195–200.
3.
WangGPierangeliSSPapalardoE, et al.Markers of oxidative and nitrosative stress in systemic lupus erythematosus: correlation with disease activity. Arthritis Rheum2010; 62(7): 2064–2072.
4.
AmesPRAlvesJMuratI, et al.Oxidative stress in systemic lupus erythematosus and allied conditions with vascular involvement. Rheumatology (Oxford)1999; 38(6): 529–534.
5.
LeitingerN. The role of phospholipid oxidation products in inflammatory and autoimmune diseases: evidence from animal models and in humans. Subcell Biochem2008; 49: 325–350.
6.
ShacterE. Quantification and significance of protein oxidation in biological samples. Drug Metab Rev2000; 32: 307–326.
7.
GrimsrudPAXieHGriffinTJ, et al.Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem2008; 283: 21837–21841.
8.
McGarryTBinieckaMVealeDJ, et al.Hypoxia, oxidative stress and inflammation. Free Radic Biol Med2018; 125: 15–24.
9.
Serdaroglu BeyazalMArpaMDevrimselG, et al.Thiol/disulphide homeostasis in patients with rheumatoid arthritis: a potential link between disease activity and preclinical atherosclerosis. Thiol/disulphide homeostasis in patients with rheumatoid arthritis: a potential link between disease activity and preclinical atherosclerosis. Acta Reumatol Port2021; 46(1): 23–31.
10.
TaysiSGulMSariRA, et al.Serum oxidant/antioxidant status of patients with systemic lupus erythematosus. Clin Chem Lab Med2002; 40(7): 684–688.
11.
TewthanomKJanwityanuchitSTotemchockchyakarnK, et al.Correlation of lipid peroxidation and glutathione levels with severity of systemic lupus erythematosus: a pilot study from single center. J Pharm Pharm Sci2008; 11(3): 30–34.
12.
ShahDSahSWanchuA, et al.Altered redox state and apoptosis in the pathogenesis of systemic lupus erythematosus. Immunobiology2013; 218(4): 620–627.
13.
ShahDWanchuABhatnagarA, et al.Interaction between oxidative stress and chemokines: possible pathogenic role in systemic lupus erythematosus and rheumatoid arthritis. Immunobiology2011; 216(9): 1010–1017.
14.
MorganPESturgessADDaviesMJ, et al.Evidence for chronically elevated serum protein oxidation in systemic lupus erythematosus patients. Free Radic Res2009; 43(2): 117–127.
15.
ShruthiSThabahMMZachariahB, et al.Association of oxidative stress with disease activity and damage in systemic lupus erythematosus: a cross sectional study from a tertiary care centre in southern India. Indian J Clin Biochem2021; 36(2): 185–193.
16.
HassanSZGheitaTAKenawySA, et al.Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relationship to disease manifestations and activity. Int J Rheum Dis2011; 14(4): 325–331.
17.
MorganPESturgessADDaviesMJ, et al.Increased levels of serum protein oxidation and correlation with disease activity in systemic lupus erythematosus. Arthritis Rheum2005; 52: 2069–2079.
18.
KundiHAtesIKiziltuncE, et al.A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med2015; 33(11): 1567–1571.
19.
JonesDPLiangY. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med2009; 47(10): 1329–1338.
20.
ErelONeseliogluS. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem2014; 47(18): 326–332.
21.
YucelASanhalCYDaglarK, et al.Thiol/disulphide homeostasis in pregnant women with Familial Mediterranean fever. Redox Rep2016; 21(6): 287–291.
22.
AtesIKaplanMYukselM, et al.Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine2016; 51(1): 47–51.
23.
GiustariniDLorenziniSRossiR, et al.Altered thiol pattern in plasma of subjects affected by rheumatoid arthritis. Clin Exp Rheumatol2005; 23(2): 205–212.
24.
TuzcuABaykaraRAOmmaA, et al.Thiol/Disulfide homeostasis in patients with rheumatoid arthritis. Rom J Intern Med2019; 57(1): 30–36.
25.
RoyDKaskiJC. Ischemia-modified albumin: the importance of oxidative stress. J Am Coll Cardiol2007; 49(24): 2375–2377.
26.
KocanHCitgezSYucetasU, et al.Can ischemia-modified albumin be used as an objective biomarker for renal ischemic damage? An experimental study with Wistar albino rats. Transplant Proc2014; 46(10): 3326–3329.
27.
TokerAMehmetogluIYerlikayaFH, et al.Investigation of oxidative stress markers in essential hypertension. Clin Lab2013; 59(1–2): 107–114.
28.
Michelle KaeferMPivaSJCarvalhoJAMD, et al.Association between ischemia modified albumin, inflammation and hyperglycemia in type 2 diabetes mellitus. Clin Biochem2010; 43: 450–454.
29.
BombardierCGladmanDDUrowitzMB, et al.Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum1992; 35(6): 630–640.
Bar-OrDLauEWinklerJV, et al.A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report. J Emerg Med2000; 19(4): 311–315.
32.
PerlA. Pathogenic mechanisms in systemic lupus erythematosus. Autoimmunity2010; 43(1): 1–6.
33.
MansourRBLassouedSGargouriB, et al.Increased levels of autoantibodies against catalase and superoxide dismutase associated with oxidative stress in patients with rheumatoid arthritis and systemic lupus erythematosus. Scand J Rheumatol2008; 37(2): 103–108.
34.
CremersCMJakobU. Oxidant sensing by reversible disulfide bond formation. J Biol Chem2013; 288(37): 26489–26496.
35.
NagyP. Kinetics and mechanisms of thiol-disulfide exchange covering direct substitution and thiol oxidation-mediated pathways. Antioxid Redox Signal2013; 18(13): 1623–1641.
36.
DogruABalkarliACetinGY, et al.Thiol/disulfide homeostasis in patients with ankylosing spondylitis. Bosn J Basic Med Sci2016; 16(3): 187–192.
37.
YilmazCNGemciogluEBaserS, et al.Thiol/disulfide homeostasis impaired in patients with primary Sjögren's syndrome. J Med Biochem2021; 40(3): 270–276.
38.
BaykaraRATuzcuAOmmaA, et al.Evaluation of serum thiol/disulfide homeostasis in patients with ankylosing spondylitis by a novel method. North Clin Istanb2018; 6(4): 348–354.
39.
ArpaMŞenBBeyazalMS, et al.Evaluation of thiol-disulfide homeostasis in active ankylosing spondylitis patients. Reumatol Clin (Engl Ed)2021; S1699–258X(21): 343–348.
40.
Ram ChanderSVarikasuvuSRAnil KumarP, et al.Ischemia modified albumin concentrations in patients with rheumatoid arthritis. Int J Rheum Dis2017; 20(12): 2152–2153.
41.
LeitemperguerMRTatschEKoberH, et al.Assessment of ischemia-modified albumin levels in patients with rheumatoid arthritis. Clin Lab2014; 60(6): 1065–1070.
42.
TürkönHGökmenFÇakirDÜ, et al.Increased levels of serum ischemia modified albumin in patients with ankylosing spondylitis. Clin Lab2016; 62(4): 645–649.
43.
SertpoyrazFMColakADikiciA, et al.The relationship of ischemia-modified albumin levels to disease activity scores and HLA-B27 in patients with ankylosing spondylitis. North Clin Istanb2020; 8(1): 42–48.
44.
BonaNPezzariniEBalbiB, et al.Oxidative stress, inflammation and disease activity biomarkers in lupus nephropathy. Lupus2020; 29(3): 311–323.
45.
AlvesJDAtherosclerosisAPR. Oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome. Immunobiology2003; 207(1): 23–28.
46.
AmesPRTommasinoCAlvesJ, et al.Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study. Lupus2000; 9(9): 688–695.
47.
HermanSZurgilNDeutschM, et al.Low dose methotrexate induces apoptosis with reactive oxygen species involvement in T lymphocytic cell lines to a greater extent than in monocytic lines. Inflamm Res2005; 54(7): 273–280.
48.
LaiZWHanczkoRBonillaE, et al.N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum2012; 64(9): 2937–2946.
49.
DohertyEOaksZPerlA, et al.Increased mitochondrial electron transport chain activity at complex I is regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus erythematosus. Antioxid Redox Signal2014; 21(1): 56–65.
