Role of CTHRC1 in Diagnosis of Rheumatoid Arthritis

NCT ID: NCT04092244

Last Updated: 2020-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-01

Study Completion Date

2021-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Rheumatoid Arthritis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Interventions

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CTHRC1 biomarker

its a biomarker detected in the serum of the patients

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Amany Abdelkader Ahmed Hefny

Resident physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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amany hefny

Role: CONTACT

+201001545631

sohair kamel

Role: CONTACT

+201024477711

References

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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.

Reference Type BACKGROUND
PMID: 29417936 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27430622 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19926660 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 10604236 (View on PubMed)

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. doi: 10.1136/ard.2005.035691. Epub 2005 May 5.

Reference Type BACKGROUND
PMID: 15878904 (View on PubMed)

Lefevre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnaker EM, Tarner IH, Robbins PD, Evans CH, Sturz H, Steinmeyer J, Gay S, Scholmerich J, Pap T, Muller-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.

Reference Type BACKGROUND
PMID: 19898488 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27182969 (View on PubMed)

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. doi: 10.1016/j.modgep.2006.03.008. Epub 2006 Mar 17.

Reference Type BACKGROUND
PMID: 16678498 (View on PubMed)

Ding B, Padyukov L, Lundstrom 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.

Reference Type BACKGROUND
PMID: 19116921 (View on PubMed)

Other Identifiers

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CTHRC1 in rheumatoid disease

Identifier Type: -

Identifier Source: org_study_id

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