Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome
1 Department of Laboratory Medicine, Section of Medical Protein Chemistry, Lund University, Inga Marie Nilsson street 53, 205 02 Malmö, Sweden
2 Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstrasse 11a, 07745 Jena, Germany
3 Department of Rheumatology and Inflammation Research, University of Gothenburg, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden
4 Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Kioskgatan 3, 221 85 Lund, Sweden
5 Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
Citation and License
Arthritis Research & Therapy 2012, 14:R185 doi:10.1186/ar4016Published: 15 August 2012
Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS.
Autoantibodies against FH, factor I (FI) and C4b-binding protein (C4BP) were measured by ELISA, while CFHR1 homozygous deletion was determined with Western blotting of sera. Epitopes for FH autoantibodies were mapped using recombinant fragments of FH.
FH autoantibodies were detected in SLE (6.7%, n = 60, RA patients (16.5%, n = 97 in the Swedish cohort and 9.2%, n = 217 in the Dutch cohort) and thrombosis patients positive for the lupus anticoagulants (LA+) test (9.4%, n = 64) compared with aHUS patients (11.7%, n = 103). In the control groups (n = 354), an average of 4% of individuals were positive for FH autoantibodies. The frequencies observed in both RA cohorts and LA+ patients were statistically significantly higher than in controls. We also found that an average of 15.2% of the FH-autoantibody positive individuals in all studied disease groups had homozygous deficiency of CFHR1 compared with 3.8% of the FH autoantibody negative patients. The levels of FH autoantibodies varied in individual patients over time. FH autoantibodies found in LA+, SLE and RA were directed against several epitopes across FH in contrast to those found in aHUS, which bound mainly to the C-terminus. Autoantibodies against FI and C4BP were detected in some patients and controls but they were not associated with any of the diseases analyzed in this study.
Autoantibodies against FH are not specific for aHUS but are present at a significant frequency in rheumatic diseases where they could be involved in pathophysiological mechanisms.