Anti-ficolin-3 Autoantibodies in Lupus Nephritis

Lupus Erythematosus, Systemic Clinical Trial

— ficolupus  

Official title:

Association Between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02625831
• Other study ID #: 1841851v0
• Status: Completed
• Phase: N/A
• First received: November 13, 2015
• Last updated: February 24, 2017
• Start date: November 2012
• Est. completion date: May 2014

Study information

• Verified date: February 2017
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: May 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

165 SLE patients

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Lupus Nephritis
• Nephritis

Intervention

Other:
• Biological analysis
Biological analysis : ficolin-3 anti-ficolin 3 antibodies anti-C1q antibodies

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	University Hospital, Marseille

References & Publications (10)

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. — View Citation

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. — View Citation

Honoré 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. — View Citation

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. — View Citation

Lacroix M, Dumestre-Pérard 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. — View Citation

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. Review. — View Citation

Orbai AM, Truedsson L, Sturfelt G, Nived O, Fang H, Alarcón 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. — View Citation

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. Erratum in: Lupus. 2011 Nov;20(13):1455. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-ficolin-3 antibodies presence in SLE patients	Anti-ficolin-3 antibodies in SLE patients, considered positive if superior than 70 arbitrary units.; This study have a single visit approach with serum collection so every outcome is measured at T0, which is the only visit for the patient.	measured at day of inclusion = T0.
Secondary	Correlation of anti-ficolin-3 antibodies with anti-DNA antibodies in SLE patients	This study have a single visit approach with serum collection so every outcome is measured at T0, which is the only visit for the patient.	measured at day of inclusion = T0.
Secondary	Correlation of anti-ficolin-3 antibodies with anti-C1q antibodies in SLE patients	This study have a single visit approach with serum collection so every outcome is measured at T0, which is the only visit for the patient.	measured at day of inclusion = T0.
Secondary	Correlation of anti-ficolin-3 antibodies with lupus activity (SLEDAI score) in SLE patients	This study have a single visit approach with serum collection so every outcome is measured at T0, which is the only visit for the patient.	measured at day of inclusion = T0.
Secondary	Anti-ficolin-3 antibodies presence in SLE patients with active nephritis	This study have a single visit approach with serum collection so every outcome is measured at T0, which is the only visit for the patient.	measured at day of inclusion = T0.