Role of CTHRC1 in Diagnosis of Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

CTHRC1 as a New Biomarker in Diagnosis of Rheumatoid Arthritis and Its Role in Seronegative Patients.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04092244
• Other study ID #: CTHRC1 in rheumatoid disease
• Status: Not yet recruiting
• Start date: August 1, 2020
• Est. completion date: December 30, 2021

Study information

• Verified date: May 2020
• Source: Assiut University
• Contact: amany hefny
• Phone: +201001545631
• Email: amany011108[@]med.aun.edu.eg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

to detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To correlate other well-established rheumatoid arthritis markers (RF& anti-ccp) and CTHRC1 level to see if CTHRC1 can act as a dependent or independent serum marker in prediction of RA status.

Description:

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease of synovial joints. Disease progression is characterized by periods of high disease activity involving both, a systemic immune response and tissue-specific inflammatory events that may lead to joint and bone destruction and subsequent disability.

Rheumatoid arthritis is a multifactorial disease with significant contribution from genetic and non-genetic factors that together account for complex disease pathology.

Diagnosis of RA is based mainly on detection of high titers of rheumatoid factor (RF) and of antibodies against cyclic citrullinated peptide (anti-CCP) or against citrullinated protein (ACPA).

The major RF species could be detected only in 60-70% of RA patients; patients with high levels of RF have higher disease activity with greater disabilities.

The problem is that RF is not a specific marker for RA and is often absent in early stages of the disease, on the other hand ACPA and CCP auto antibodies provide high specificity but moderate sensitivity, adding to that CRP and ESR are general indicators of inflammation and are not specific for RA.

Collagen triple helix repeat containing 1 protein (CTHRC1) is expressed in a number of embryonic and neonate tissues, including developing cartilage and bone. It is a secreted modulator of Wnt signaling, which is a key regulator of joint remodeling and promotes cell proliferation and migration.

Immunohistochemical analysis of various human primary cancers and metastases has revealed that CTHRC1 expression is actually limited to the stromal cells of solid tumors.

The expression of CTHRC1 encoding gene was found to be strongly associated with the severity of murine collagen antibody-induced arthritis.

Arthritic pannus is a multicellular vascularized tissue composed of cells of both mesenchymal and hematopoietic origin, including synovial fibroblasts, osteoclasts, endothelial cells, dendritic cells, monocytes/macrophages, as well as T and B cells that contribute to the development and progression of joint and cartilage erosion through secretion of pro-inflammatory cytokines and tissue-degrading proteases. Fibroblast-like synoviocytes (FLS), particularly the invasive and migratory cadherin-11-positive subtype, are major components of synovial pannus tissue and are considered active drivers in the pathogenesis of RA.

The expression of CTHRC1 in pannus and its role in the function of FLS relevant to cartilage damage in RA make it of great value if used as a blood-based biomarker for improved diagnosis of rheumatoid arthritis patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: December 30, 2021
• Est. primary completion date: November 28, 2021
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• All RA patients must fulfill the 2010 ACR/EULAR criteria for RA.

• Healthy individual must be without a prior history of chronic inflammation or any form of arthritis.

Exclusion Criteria:

• - Patients with solid tumors.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Diagnostic Test:
• CTHRC1 biomarker
its a biomarker detected in the serum of the patients

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (9)

Ding B, Padyukov L, Lundström E, Seielstad M, Plenge RM, Oksenberg JR, Gregersen PK, Alfredsson L, Klareskog L. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. Arthritis Rheum. 2009 Jan;60(1):30-8. doi: 10.1002/art.24135. Erratum in: Arthritis Rheum. 2009 Apr;60(4):1200. — View Citation

Durmus T, LeClair RJ, Park KS, Terzic A, Yoon JK, Lindner V. Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1). Gene Expr Patterns. 2006 Oct;6(8):935-40. Epub 2006 Mar 17. — View Citation

Han B, Pouget JG, Slowikowski K, Stahl E, Lee CH, Diogo D, Hu X, Park YR, Kim E, Gregersen PK, Dahlqvist SR, Worthington J, Martin J, Eyre S, Klareskog L, Huizinga T, Chen WM, Onengut-Gumuscu S, Rich SS; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray NR, Raychaudhuri S. A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases. Nat Genet. 2016 Jul;48(7):803-10. doi: 10.1038/ng.3572. Epub 2016 May 16. — View Citation

Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnäker EM, Tarner IH, Robbins PD, Evans CH, Stürz H, Steinmeyer J, Gay S, Schölmerich J, Pap T, Müller-Ladner U, Neumann E. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. 2009 Dec;15(12):1414-20. doi: 10.1038/nm.2050. Epub 2009 Nov 8. — View Citation

Nell VP, Machold KP, Stamm TA, Eberl G, Heinzl H, Uffmann M, Smolen JS, Steiner G. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005 Dec;64(12):1731-6. Epub 2005 May 5. — View Citation

Shekhani MT, Forde TS, Adilbayeva A, Ramez M, Myngbay A, Bexeitov Y, Lindner V, Adarichev VA. Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus. Arthritis Res Ther. 2016 Jul 19;18:171. doi: 10.1186/s13075-016-1067-1. — View Citation

Singal DP, Li J, Zhu Y. Genetic basis for rheumatoid arthritis. Arch Immunol Ther Exp (Warsz). 1999;47(5):307-11. Review. — View Citation

Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1. Review. — View Citation

Song YW, Kang EH. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies. QJM. 2010 Mar;103(3):139-46. doi: 10.1093/qjmed/hcp165. Epub 2009 Nov 19. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	detect value of CTHRC1 in diagnosis of rheumatoid arthritis	detect the role of CTHRC1 biomarker in diagnosis of rheumatoid arthritis and To compare the sensitivity and the specificity of CTHRC1 in relation to other biomarkers used in diagnosis of RA.	baseline