Document Type : Original Article

Authors

Departments of Pathology and Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

BACKGROUND: Rheumatoid arthritis (RA) is a common multisystemic autoimmune disease with
peripheral joint involvement. Many autoantibodies have been introduced in the course of RA; some of
them have diagnostic and prognostic value. In this study, our aim is to determine the value of serum
glucose‑6‑phosphate isomerase (G6PI) antigen (Ag) as a diagnostic and prognostic marker in RA.
MATERIALS AND METHODS: Eighty‑seven known cases of RA who referred to an outpatient
clinic of Shiraz University of Medical Sciences and 76 healthy controls were selected. Serum G6PI
Ag was measured using sandwich enzyme‑linked immunosorbent assay method, and the enzyme
level was compared in the patient and control group, we also compared the enzyme level of patient
group with disease activity, disease duration, erythrocyte sedimentation rate (ESR), C‑reactive
protein (CRP), rheumatoid factor (RF), and anti‑cyclic citrullinated peptide (anti‑CCP) antibody (Ab).
The data were analyzed using SPSS V 16 software.
RESULTS: Positivity for G6PI was detected in 34.5% (30/87) of RA patients and 9.2% (7/76) of
control group (P < 0.001). There was no significant correlation between enzyme level and disease
activity, disease duration, ESR, CRP, RF, and anti‑CCP Ab.
CONCLUSIONS: Overall, in our study, although there was a significant difference in serum G6PI
Ag between patient and control group, no significant correlation was detected between serum G6PI
level and disease activity score, ESR, CRP, and anti‑CCP Ab, but relative correlation with ESR and
disease duration could be challenging. G6PI Ag could be introduced as a diagnostic marker in RA,
but its role as a prognostic marker is controversial.

Keywords

1. Gabriel SE, Crowson CS. Epidemiology of Risk Factors for, and
Possible Causes of Rheumatoid Arthritis. Up to Date; December,
2018.
2. McPherson R, Pincus M, Abraham N, Bluth M, Bock J,
Hutchinson R, et al. Henry’s Clinical Diagnosis and Management
by Laboratory Methods. 22nd ed.. Philadelphia: Saunders/Elsevier;
2011. p. 980‑3.
3. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL,
Loscalzo J. Harrison’s Principles of Internal Medicine. 18th ed.
New York: Mc Graw‑Hill; 2011. p. 2738‑52.
4. Dai L, Zhu LJ, Zheng DH, Mo YQ, Wei XN, Su JH, et al. Elevated
serum glucose‑6‑phosphate isomerase correlates with histological
disease activity and clinical improvement after initiation of
therapy in patients with rheumatoid arthritis. J Rheumatol
2010;37:2452‑61.
5. Schaller M, Burton DR, Ditzel HJ. Autoantibodies to GPI in
rheumatoid arthritis: Linkage between an animal model and
human disease. Nat Immunol 2001;2:746‑53.
6. Van Gaalen FA, Toes RE, Ditzel HJ, Schaller M, Breedveld FC,
Verweij CL, et al. Association of autoantibodies to
glucose‑6‑phosphate isomerase with extraarticular complications
in rheumatoid arthritis. Arthritis Rheum 2004;50:395‑9.
7. McWilliams DF, Kiely PD, Young A, Joharatnam N, Wilson D,
Walsh DA. Interpretation of DAS 28 and its components in the
assessment of inflammatory and non‑inflammatory aspects of
rheumatoid arthritis. BMC Rheumatology 2018;2:8.
8. Yang D, Ge H, Dong J, Zhu X, Sun G, Ouyang W, et al. The
diagnostic significance of glucose‑6‑phosphate isomerase (G6PI)
antigen and anti‑G6PI antibody in rheumatoid arthritis patients.
Adv Biosci Biotechnol 2013;4:818‑22.
9. Maksymowych WP, Boire G, van Schaardenburg D, Wichuk S,
Turk S, Boers M, et al. 14‑3‑3η autoantibodies: Diagnostic use in
early rheumatoid arthritis. J Rheumatol 2015;42:1587‑94.
10. Chang PY, Yang CT, Cheng CH, Yu KH. Diagnostic performance
of anti‑cyclic citrullinated peptide and rheumatoid factor in
patients with rheumatoid arthritis. Int J Rheum Dis 2016;19:880‑6.11. Kugler W, Lakomek M. Glucose‑6‑phosphate isomerase
deficiency. Baillieres Best Pract Res Clin Haematol 2000;13:89‑101.
12. Haga A, Niinaka Y, Raz A. Phosphohexose isomerase/autocrine
motility factor/neuroleukin/maturation factor is a multifunctional
phosphoprotein. Biochim Biophys Acta 2000;1480:235‑44.
13. Lu Y, Yu SS, Zong M, Fan SS, Lu TB, Gong RH, et al.
Glucose‑6‑phosphate isomerase (G6PI) mediates hypoxia‑induced
angiogenesis in rheumatoid arthritis. Sci Rep 2017;7:40274.
14. Zong M, Lu T, Fan S, Zhang H, Gong R, Sun L, et al.
Glucose‑6‑phosphate isomerase promotes the proliferation
and inhibits the apoptosis in fibroblast‑like synoviocytes in
rheumatoid arthritis. Arthritis Res Ther 2015;17:100.
15. Schaller M, Stohl W, Benoit V, Tan SM, Johansen L, Ditzel HJ,
et al. Patients with inflammatory arthritic diseases harbor elevated
serum and synovial fluid levels of free and immune‑complexed
glucose‑6‑phosphate isomerase (G6PI). Biochem Biophys Res
Commun 2006;349:838‑45.
16. Fan LY, Zong M, Wang Q, Yang L, Sun LS, Ye Q, et al. Diagnostic
value of glucose‑6‑phosphate isomerase in rheumatoid arthritis.
Clin Chim Acta 2010;411:2049‑53.