Anti-ficolin-3 Autoantibodies in Lupus Nephritis

NCT02625831 | Completed

• 1 other identifier: 1841851v0
• Study Type: observational
• Target: 213
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Lupus Erythematosus, Systemic

Keywords

ficolin-3; anti-ficolin-3 antibodies; lupus nephritis; Lupus Erythematosus, Systemic; biomarker

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Correlation of anti-ficolin-3 antibodies with anti-DNA antibodies in SLE patients

  measured at day of inclusion = T0.

• Correlation of anti-ficolin-3 antibodies with anti-C1q antibodies in SLE patients

  measured at day of inclusion = T0.

• Correlation of anti-ficolin-3 antibodies with lupus activity (SLEDAI score) in SLE patients

  measured at day of inclusion = T0.

• Anti-ficolin-3 antibodies presence in SLE patients with active nephritis

  measured at day of inclusion = T0.

Study Arms (2)

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.

Other: Biological analysis

healthy patients

48 healthy patients. Biological analysis were performed.

Other: Biological analysis

Interventions

Biological analysis OTHER

Biological analysis : * ficolin-3 * anti-ficolin 3 antibodies * anti-C1q antibodies

Also known as: Biological analysis on pre-existing serum collection

SLE patients; healthy patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

SLE patients were studied from medical data files of the Departments of Internal Medicine (Grenoble University Hospital, France) and Nephrology (Conception University Hospital, Marseille, France). For SLE patients, clinical and biological manifestations as well as treatments received and disease activity evaluated using the SLE Disease Activity Index (SLEDAI) at the time of sampling were recorded. SLE patients were divided into subgroups as described in group section.

You may qualify if:

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

You may not qualify if:

• Pregnant women
• Patient with known evolutive cancer
• healthy patients matched in age and sex with one or several SLE patients

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• University Hospital, Marseille: collaborator

Related 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. Epub 2009 Feb 4.

  PMID: 19208603 BACKGROUND

• 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.

  PMID: 9663482 BACKGROUND

• 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.

  PMID: 17469142 BACKGROUND

• 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.

  PMID: 20360925 BACKGROUND

• 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.

  PMID: 25124676 BACKGROUND

• 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.

  PMID: 9293379 BACKGROUND

• 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.

  PMID: 21893562 BACKGROUND

• 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.

  PMID: 15804047 BACKGROUND

• 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.

  PMID: 19109177 BACKGROUND

• 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.

  PMID: 15147364 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

one serum sample per patient.

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Interventions

Biological Oxygen Demand Analysis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Environmental Monitoring; Environmental Exposure; Environmental Pollution; Public Health; Environment and Public Health; Public Health Practice

Study Officials

• Chantal DUMESTRE-PERARD, PhD

  University Hospital Grenoble, FRANCE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2015
• First Posted: December 9, 2015
• Study Start: November 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: February 28, 2017

Record last verified: 2017-02