Assessment of Wnt-5a, Anti-SMA, FGF-23, and Anti-CCP Biomarkers in Patients with Rheumatoid Arthritis


  • Bahramand Babatahir Marouf Department of Microbiology/Immunology, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Kawa Abdulla Muhammed Amin Department of Microbiology/Immunology, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq. & Department of Medical Science, Respiratory Medicine, and Allergology, Uppsala University and University Hospital, Uppsala, Sweden. Author
  • Heshu Sulaiman Rahman Department of Physiology, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq. Author



Rheumatoid arthritis, serum biomarkers, case-control study, autoimmune disease


Background: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease with unknown etiology that mainly affects synovial joints.


Objectives: To compare the level of serum biomarkers (Wnt5a, anti-SMA, FGF23, and anti-CCP) in RA patients and healthy control.


Methodology: This case-control study was conducted on 88 patients with RA and 88 normal healthy individuals at the Rheumatology Center, Sulaimaniyah, from November 2021 to November 2022. A detailed questionnaire for the collection of sociodemographic measures was filled out for each participant. Then, the levels of Wnt5a, anti-SMA, FGF23, and anti-CCP were determined using the ELISA technique.


Results: The patients reported higher levels of ESR and CRP than healthy controls. Most patients (63.7%) had moderate disease activity concerning DAS-28. There was a highly significant difference (p<0.001) between patients’ serum Wnt5a, FGF23, and anti-CCP levels compared to healthy controls except for anti-SMA. Additionally, there was a significant correlation between Wnt5a and FGF23 (p<0.001); Wnt5a and anti-SMA (p<0.001); FGF23 and anti-SMA (p<0.001). Finally, no correlation between the DAS-28 score and biomarkers was seen in RA patients.


Conclusions: There was no significant correlation in the patient’s serum Wnt5a, FGF23, anti-SMA, and anti-CCP with different age groups, duration of RA and joint involvements.


Sparks JA, He X, Huang J, Fletcher EA, Zaccardelli A, Friedlander HM, et al. (2019). Rheumatoid arthritis

disease activity predicting incident clinically apparent rheumatoid arthritis–associated interstitial lung disease:

a prospective cohort study. Arthritis Rheumatol. 71(9):1472–82.

Bullock J, Rizvi SAA, Saleh AM, Ahmed SS, Do DP, Ansari RA, et al. (2018). Rheumatoid arthritis: a brief

overview of the treatment. Med Princ Pract. 27(6):501–7.

Scherer HU, Häupl T, Burmester GR. (2020). The etiology of rheumatoid arthritis. J Autoimmun. DOI:


Garland SG, Falk NP. (2022). Rheumatoid Arthritis and Related Disorders. In: Family Medicine: Principles DOI:

and Practice. Springer; p. 1615–34.

Asif Amin M, Fox DA, Ruth JH. (2017). Synovial cellular and molecular markers in rheumatoid arthritis. DOI:

In: Seminars in immunopathology. Springer; p. 385–93.

Rafiq SB, Rahman HS, Amin K. (2020). The Estimate of Cytokines and Fibroblast Growth Factors in DOI:

Patients with Breast Cancer. J Zankoy Sulaimani. 22(2):9–16.

Bouksila M, Mrad M, Kaabachi W, Kalai E, Smaoui W, Rekik S, et al. (2019). Correlation of Fgf23 and

balp with bone mineral density in hemodialysis patients. J Med Biochem. 38(4):418.

Sato H, Kazama JJ, Murasawa A, Otani H, Abe A, Ito S, et al. (2016). Serum fibroblast growth factor 23

(FGF23) in patients with rheumatoid arthritis. Intern Med. 55(2):121–6. DOI:

Kobayashi Y, Maeda K, Takahashi N. (2008). Roles of Wnt signaling in bone formation and resorption. Jpn DOI:

Dent Sci Rev. 44(1):76–82.

Cici D, Corrado A, Rotondo C, Cantatore FP. (2019). Wnt signaling and biological therapy in rheumatoid

arthritis and spondyloarthritis. Int J Mol Sci. 20(22):5552.

Andersen I, Andersen P, Graudal H. (1980). Smooth‐muscle antibodies in rheumatoid arthritis. Acta Pathol DOI:

Microbiol Scand Sect C Immunol. 88(1‐6):131–6.

Song HY, Kim MY, Kim KH, Lee IH, Shin SH, Lee JS, et al. (2010). Synovial fluid of patients with

rheumatoid arthritis induces α-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells

through a TGF-β1-dependent mechanism. Exp Mol Med. 42(8):565–73.

Mimori T. (2005). Clinical significance of anti-CCP antibodies in rheumatoid arthritis. Intern Med. DOI:


Zamanpoor M. (2019). The genetic pathogenesis, diagnosis and therapeutic insight of rheumatoid arthritis. DOI:

Clin Genet. 95(5):547–57.

Singh A, Behl T, Sehgal A, Singh S, Sharma N, Naqwi M, et al. (2022). Exploring the role of exosomes in

rheumatoid arthritis. Inflammopharmacology. 1–10.

Mody GM, Cardiel MH. (2008). Challenges in the management of rheumatoid arthritis in developing DOI:

countries. Best Pract Res Clin Rheumatol. 22(4):621–41.

Pawłowska J, Smoleńska Ż, Daca A, Witkowski JM, Bryl E. (2011). Older age of rheumatoid arthritis

onset is associated with higher activation status of peripheral blood CD4+ T cells and disease activity. Clin

Exp Immunol. 163(2):157–64.

Ljung L, Rantapää-Dahlqvist S. (2016). Abdominal obesity, gender and the risk of rheumatoid arthritis–a DOI:

nested case–control study. Arthritis Res Ther. 18(1):1–8.

Serhal L, Lwin MN, Holroyd C, Edwards CJ. (2020). Rheumatoid arthritis in the elderly: characteristics

and treatment considerations. Autoimmun Rev. 19(6):102528.

Gerosa M, De Angelis V, Riboldi P, Meroni PL. (2008). Rheumatoid arthritis: a female challenge. DOI:

Women’s Heal. 4(2):195–201.

Linauskas A, Overvad K, Symmons D, Johansen MB, (2019). Stengaard‐Pedersen K, De Thurah A. Body

fat percentage, waist circumference, and obesity as risk factors for rheumatoid arthritis: a Danish cohort study.

Arthritis Care Res (Hoboken). 71(6):777–86.

Marchand NE, Sparks JA, Tedeschi SK, Malspeis S, Costenbader KH, Karlson EW, et al. (2021).

Abdominal obesity in comparison with general obesity and risk of developing rheumatoid arthritis in women.

J Rheumatol. 48(2):165–73.

Dzieża-Grudnik A, Sulicka J, Strach M, Siga O, Klimek E, Korkosz M, et al. (2017). Arterial stiffness is

not increased in patients with short duration rheumatoid arthritis and ankylosing spondylitis. Blood Press.


Vázquez-Del Mercado M, Gomez-Bañuelos E, Chavarria-Avila E, Cardona-Muñoz E, Ramos-Becerra C,

Alanis-Sanchez A, et al. (2017). Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a

cross-sectional study in patients without known cardiovascular comorbidities: A STROBE-compliant article.

Medicine (Baltimore). 96(33).

Karimifar M, Salesi M, Farajzadegan Z. (2012). The association of anti-CCP1 antibodies with disease DOI:

activity score 28 (DAS-28) in rheumatoid arthritis. Adv Biomed Res. 1.

Shafiaa S, Shaha ZA, Sofib FA, Rasoola R, Gulla A. (2016). Anti-CCP is associated with greater disease

burden in Kashmiri population with rheumatoid arthritis. Rheumatol. 6(1):190.

Lal AR, Babu C, Jijo J, Aravindan LJ, Vijayakumar K, Mithun CB. (2020). Adherence to Methotrexate

therapy in patients with rheumatoid arthritis-a hospital based cross sectional study from Kochi, Kerala. Natl J

Res Community Med. 9(3):100–5.

Jiang X, Frisell T, Askling J, Karlson EW, Klareskog L, Alfredsson L, et al. (2015). To what extent is the

familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors? Arthritis

Rheumatol. 67(2):352–62.

Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. (2017). Genetic and

environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 31(1):3–18. DOI:

Deane KD, Holers VM. (2019). The natural history of rheumatoid arthritis. Clin Ther. 41(7):1256–69. DOI:

Kurkó J, Besenyei T, Laki J, Glant TT, Mikecz K, Szekanecz Z. (2013). Genetics of rheumatoid arthritis—

a comprehensive review. Clin Rev Allergy Immunol. 45:170–9.

Hedström AK, Stawiarz L, Klareskog L, Alfredsson L. (2018). Smoking and susceptibility to rheumatoid

arthritis in a Swedish population-based case–control study. Eur J Epidemiol. 33(4):415–23. DOI:

Seror R, Henry J, Gusto G, Aubin HJ, Boutron-Ruault MC, Mariette X. (2019). Passive smoking in

childhood increases the risk of developing rheumatoid arthritis. Rheumatology. 58(7):1154–62. DOI:

Cappelli LC, Konig MF, Gelber AC, Bingham CO, Darrah E. (2018). Smoking is not linked to the

development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis. Arthritis Res Ther.


Gračanin AG, Marković I, Golob M, Lucijanić M, Valetić AM, Morović-Vergles J. (2020). The effect of

smoking on disease activity in rheumatoid arthritis–our experience. Acta Clin Croat. 59(2):312.

Chang K, Yang SM, Kim SH, Han KH, Park SJ, Shin J Il. (2014). Smoking and rheumatoid arthritis. Int J DOI:

Mol Sci. 15(12):22279–95.

Gavrilă BI, Ciofu C, Stoica V. (2016). Biomarkers in rheumatoid arthritis, what is new? J Med Life.


Ma MHY, Defranoux N, Li W, Sasso EH, Ibrahim F, Scott DL, et al. (2020). A multi-biomarker disease

activity score can predict sustained remission in rheumatoid arthritis. Arthritis Res Ther. 22(1):1–12.

Matuszewska A, Madej M, Wiland P. (2016). Markery immunologiczne reumatoidalnego zapalenia

stawów. Adv Hyg Exp Med Hig i Med Dosw. 70.

Tiwari V, Jandu JS, Bergman MJ. (2022). Rheumatoid Factor. In: StatPearls [Internet]. StatPearls


Manivelavan D, Vijayasamundeeswari CK. (2012). Anti-cyclic citrullinated peptide antibody: an early

diagnostic and prognostic biomarker of rheumatoid arthritis. J Clin Diagnostic Res JCDR. 6(8):1393.

Orr CK, Najm A, Young F, McGarry T, Biniecka M, Fearon U, et al. (2018). The utility and limitations of

CRP, ESR and DAS28-CRP in appraising disease activity in rheumatoid arthritis. Front Med. 5:185.

Curtis JR, Greenberg JD, Harrold LR, Kremer JM, Palmer JL. (2018). Influence of obesity, age, and

comorbidities on the multi-biomarker disease activity test in rheumatoid arthritis. In: Seminars in arthritis and

rheumatism. Elsevier; p. 472–7.

Xiao CY, Pan YF, Guo XH, Wu YQ, Gu JR, Cai DZ. (2011). Expression of β-catenin in rheumatoid

arthritis fibroblast-like synoviocytes. Scand J Rheumatol. 40(1):26–33.

Yu M, Guo Y, Zhang P, Xue J, Yang J, Cai Q, et al. (2019). Increased circulating Wnt5a protein in patients

with rheumatoid arthritis-associated interstitial pneumonia (RA-ILD). Immunobiology. 224(4):551–9. DOI:

Çelik DŞ, Ayar K, Ermurat S, Üstündağ Y. (2022). Fibroblast growth factor 23 (Fgf23) levels and their

relationship with disease activity, bone mineral density, and radiological damage score in patients with

rheumatoid arthritis: a single center case–control study. Egypt Rheumatol Rehabil. 49():50.

Chang P, Yang C, Cheng C, Yu K. (2016). Diagnostic performance of anti‐cyclic citrullinated peptide and

rheumatoid factor in patients with rheumatoid arthritis. Int J Rheum Dis. 19(9):880–6.

Pramod GR, Dihingia P, Jha AK, Gadgade A, Agarwal D. (2022). Rheumatoid arthritis co-relation with

anti-CCP antibodies with special reference to its prevalence in asymptomatic first-degree relatives. Mediterr J

Rheumatol. 33(1):42.

Yasmin R, Sarker HN. (2022). Anti-CCP antibody in rheumatoid arthritis patients and its relation with DOI:

severity of the disease. BIRDEM Med J. 12(1):36–40.



How to Cite

Assessment of Wnt-5a, Anti-SMA, FGF-23, and Anti-CCP Biomarkers in Patients with Rheumatoid Arthritis. (2023). Journal of Zankoy Sulaimani - Part A, 25(2), 12.

Most read articles by the same author(s)