Anti-ficolin-3 Autoantibodies in Lupus Nephritis

NCT ID: NCT02625831

Last Updated: 2017-02-28

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

COMPLETED

Total Enrollment

213 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-11-30

Study Completion Date

2014-05-31

Brief Summary

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE.

In this retrospective study, clinical data were obtained from medical files and blood samples were selected from preexisting biological collection. SLE patients (n=165) were informed and did not objected, they were matched to healthy controls (n=48). Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 58 of 165 (35%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (p\<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, only the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p=0.0001). This association with renal involvement was higher with anti-ficolin-3 antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other traditional biomarker.

These results suggest that anti-ficolin-3 could be useful for the diagnosis of active nephritis in SLE patients.

Detailed Description

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For this retrospective study, a brief summary should be enough.

Conditions

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Lupus Erythematosus, Systemic

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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SLE patients

165 SLE patients. Subgroup : 77 with active lupus and 88 in disease remission. in the active subgroup : 36 with lupus nephritis and 41 without.

Biological analysis were performed.

Biological analysis

Intervention Type OTHER

Biological analysis :

* ficolin-3
* anti-ficolin 3 antibodies
* anti-C1q antibodies

healthy patients

48 healthy patients. Biological analysis were performed.

Biological analysis

Intervention Type OTHER

Biological analysis :

* ficolin-3
* anti-ficolin 3 antibodies
* anti-C1q antibodies

Interventions

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Biological analysis

Biological analysis :

* ficolin-3
* anti-ficolin 3 antibodies
* anti-C1q antibodies

Intervention Type OTHER

Other Intervention Names

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Biological analysis on pre-existing serum collection

Eligibility Criteria

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Inclusion Criteria

* Age: ≥ 18 years old
* Patients with lupus diagnostic criteria (ACR1997)

Exclusion Criteria

* Pregnant women
* Patient with known evolutive cancer

48 healthy patients matched in age and sex with one or several SLE patients
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Marseille

OTHER

Sponsor Role collaborator

University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chantal DUMESTRE-PERARD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Grenoble, FRANCE

References

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Andersen T, Munthe-Fog L, Garred P, Jacobsen S. Serum levels of ficolin-3 (Hakata antigen) in patients with systemic lupus erythematosus. J Rheumatol. 2009 Apr;36(4):757-9. doi: 10.3899/jrheum.080361. Epub 2009 Feb 4.

Reference Type BACKGROUND
PMID: 19208603 (View on PubMed)

Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum. 1998 Jul;41(7):1241-50. doi: 10.1002/1529-0131(199807)41:73.0.CO;2-H.

Reference Type BACKGROUND
PMID: 9663482 (View on PubMed)

Honore C, Hummelshoj T, Hansen BE, Madsen HO, Eggleton P, Garred P. The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells. Arthritis Rheum. 2007 May;56(5):1598-607. doi: 10.1002/art.22564.

Reference Type BACKGROUND
PMID: 17469142 (View on PubMed)

Liphaus BL, Kiss MH. The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus. Clinics (Sao Paulo). 2010 Mar;65(3):327-33. doi: 10.1590/S1807-59322010000300014.

Reference Type BACKGROUND
PMID: 20360925 (View on PubMed)

Orbai AM, Truedsson L, Sturfelt G, Nived O, Fang H, Alarcon GS, Gordon C, Merrill J, Fortin PR, Bruce IN, Isenberg DA, Wallace DJ, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke AE, Aranow CB, Manzi S, Urowitz MB, Gladman DD, Kalunian KC, Costner MI, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, Van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS, Petri M. Anti-C1q antibodies in systemic lupus erythematosus. Lupus. 2015 Jan;24(1):42-9. doi: 10.1177/0961203314547791. Epub 2014 Aug 14.

Reference Type BACKGROUND
PMID: 25124676 (View on PubMed)

Yoshizawa S, Nagasawa K, Yae Y, Niho Y, Okochi K. A thermolabile beta 2-macroglycoprotein (TMG) and the antibody against TMG in patients with systemic lupus erythematosus. Clin Chim Acta. 1997 Aug 29;264(2):219-25. doi: 10.1016/s0009-8981(97)00078-8. No abstract available.

Reference Type BACKGROUND
PMID: 9293379 (View on PubMed)

Sato N, Ohsawa I, Nagamachi S, Ishii M, Kusaba G, Inoshita H, Toki A, Horikoshi S, Ohi H, Matsushita M, Tomino Y. Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis. Lupus. 2011 Nov;20(13):1378-86. doi: 10.1177/0961203311415561. Epub 2011 Sep 5.

Reference Type BACKGROUND
PMID: 21893562 (View on PubMed)

Kuraya M, Ming Z, Liu X, Matsushita M, Fujita T. Specific binding of L-ficolin and H-ficolin to apoptotic cells leads to complement activation. Immunobiology. 2005;209(9):689-97. doi: 10.1016/j.imbio.2004.11.001.

Reference Type BACKGROUND
PMID: 15804047 (View on PubMed)

Lacroix M, Dumestre-Perard C, Schoehn G, Houen G, Cesbron JY, Arlaud GJ, Thielens NM. Residue Lys57 in the collagen-like region of human L-ficolin and its counterpart Lys47 in H-ficolin play a key role in the interaction with the mannan-binding lectin-associated serine proteases and the collectin receptor calreticulin. J Immunol. 2009 Jan 1;182(1):456-65. doi: 10.4049/jimmunol.182.1.456.

Reference Type BACKGROUND
PMID: 19109177 (View on PubMed)

Takahashi R, Tsutsumi A, Ohtani K, Goto D, Matsumoto I, Ito S, Wakamiya N, Sumida T. Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic lupus erythematosus. Clin Exp Immunol. 2004 Jun;136(3):585-90. doi: 10.1111/j.1365-2249.2004.02477.x.

Reference Type BACKGROUND
PMID: 15147364 (View on PubMed)

Other Identifiers

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1841851v0

Identifier Type: -

Identifier Source: org_study_id

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