Anti-ficolin-2 Autoantibodies in Lupus Nephritis

Lupus Erythematosus, Systemic Clinical Trial

— Ficolupus2  

Official title:

Association Between the Presence of Autoantibodies Targeting Ficolin-2 and Active Nephritis in Patients With Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03063281
• Other study ID #: 2030950v0
• Status: Completed
• Phase: N/A
• First received: February 21, 2017
• Last updated: February 21, 2017
• Start date: November 2012
• Est. completion date: May 2015

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. The prevalence and significance of antibodies against Ficolin-2 have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-2 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE.

This study is a secondary phase of a serum sample analysis done in early 2015 in order to determine the prevalence of anti-ficolin-2 antibodies among the same cohort as the previously declared study (ClinicalTrials.gov ID: NCT02625831; Unique Protocol ID: 1841851v0).

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-2 antibodies levels were measured in sera by ELISA and correlated to previously obtained Anti-ficolin-3, Anti-ficolin-2, anti-dsDNA and anti-C1q antibodies levels.

The titer of anti-ficolin-2 antibodies was correlated with the SLEDAI score (p<0.0001). The presence of anti-ficolin-2 antibodies was associated with anti-ficolin-3 antibodies, anti-C1q and anti-dsDNA antibodies.

Interestingly, the combination of anti-ficolin-3, anti-ficolin-2 and anti-C1q antibodies demonstrated higher specificity than any other traditional biomarker.

These results suggest that anti-ficolin-3 and anti-ficolin-2 antibodies could be useful for the diagnosis of active nephritis in SLE patients.

Description:

For this retrospective study, the well written brief summary should be sufficient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: May 2015
• 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-2 et anti-ficolin-2 antibodies

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	University Hospital, Marseille

References & Publications (9)

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

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

Plawecki M, Lheritier E, Clavarino G, Jourde-Chiche N, Ouili S, Paul S, Gout E, Sarrot-Reynauld F, Bardin N, Boëlle PY, Chiche L, Bouillet L, Thielens NM, Cesbron JY, Dumestre-Pérard C. Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus. PLoS One. 2016 Sep 15;11(9):e0160879. doi: 10.1371/journal.pone.0160879. — 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

Tanha N, Pilely K, Faurschou M, Garred P, Jacobsen S. Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus. Clin Rheumatol. 2017 Feb;36(2):335-341. doi: 10.1007/s10067-016-3508-2. — View Citation

Watanabe H, Saito R, Asano T, Sato S, Iwadate H, Kobayashi H, Ohira H. Serum L-ficolin levels in patients with systemic lupus erythematosus. Mod Rheumatol. 2012 Nov;22(6):899-902. doi: 10.1007/s10165-012-0616-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-ficolin-2 antibodies presence in SLE patients	Anti-ficolin-2 antibodies in SLE patients, considered positive if superior than 95 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-2 antibodies with anti-DNA antibodies in SLE patients	Correlation between Anti-ficolin-2 antibodies presence and anti-DNA antibodies presence.; 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-2 antibodies with anti-C1q antibodies in SLE patients	Correlation between Anti-ficolin-2 antibodies presence and anti-C1q antibodies presence.; 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-2 antibodies with lupus activity (SLEDAI score) in SLE	Correlation between Anti-ficolin-2 antibodies presence and clinical and/or biological evidence of SLE activity according to SLEDAI score (2012).; 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-2 antibodies presence with active nephritis in SLE patients	Correlation between Anti-ficolin-2 antibodies presence and clinical and/or biological evidence of 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