title: Markers of childhood lupus nephritis indicating disease activity.
abstract: Current treatment regimens for childhood lupus nephritis (LN) are associated with significant side-effects and toxicity in vulnerable phases of growth and development. The paucity of biomarkers particularly in childhood impedes the appropriate clinical management and the development of new therapeutics. We analyzed markers of immune system (BAFF, RANTES), complement (Bb, C1q, C3d-CIC, C5a) and endothelial cell activation (sVCAM-1) in children with LN (n=22, mean age 14.8±4.7 years), nephrotic syndrome (n=13) and age-matched healthy controls (n=20) to define parameters that correlate with LN activity. Complement fragments of the alternative (Bb, p=0.0004) classical (C3d-CIC, p<0.0001) and common pathway (C5a, p<0.0001) and the levels of BAFF (p<0.0001), RANTES (p=0.0002) and sVCAM-1 (p=0.0004) were significantly higher in active compared to inactive LN. Activation of complement was associated with the occurrence of anti-C1q antibodies and reduced complement C1q. Complement-activation fragments highly correlated with the markers for immune system and endothelial cell activation. The ensemble of these parameters may be of great value in identifying early flares or remissions of childhood LN, and moreover may prove useful in the assessment of new treatments and in determining the optimization of their use.
authors.affiliation: Department of Pediatrics I, Innsbruck Medical University, Anichstr. 35, 6020, Innsbruck, Austria. monika.edelbauer@i-med.ac.at
authors.forename: Monika
authors.initials: M
authors.lastname: Edelbauer
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kshirsagar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Riedl
authors.forename: Dieter
authors.initials: D
authors.lastname: Haffner
authors.forename: Heiko
authors.initials: H
authors.lastname: Billing
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
authors.forename: Sophia
authors.initials: S
authors.lastname: Ross
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.forename: Oliver
authors.initials: O
authors.lastname: Amon
authors.forename: Henry
authors.initials: H
authors.lastname: Fehrenbach
authors.forename: Christian
authors.initials: C
authors.lastname: Steuber
authors.forename: Antje
authors.initials: A
authors.lastname: Beissert
authors.forename: Josef
authors.initials: J
authors.lastname: Hager
authors.forename: Gottfried
authors.initials: G
authors.lastname: Wechselberger
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.forename: Lothar Bernd
authors.initials: LB
authors.lastname: Zimmerhackl
mesh_terms: D000293:Adolescent; D001317:Austria; D053264:B-Cell Activating Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood; D002648:Child; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005858:Germany; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016014:Linear Models; D008181:Lupus Nephritis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods*; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D007166:Immunosuppressive Agents; C505719:TNFSF13B protein, human; D019010:Vascular Cell Adhesion Molecule-1; D003165:Complement System Proteins