Factor H (FH)
autoantibodies are present in 6-10% of
atypical hemolytic uremic syndrome (aHUS) patients, most of whom have homozygous deficiency of the FH-related
protein FHR-1. Although the pathogenic role of the
autoantibodies is established, little is known about their molecular characteristics and changes over time. Here, we describe the specificity and other immunological features of anti-FH
autoantibodies in the Spanish and Hungarian aHUS cohorts. A total of 19 patients were included and serial samples of 14 of them were available. FH
autoantibodies from FHR-1 deficient patients (n=13) mainly recognized FH, its SCR19-20 fragment and FHR-1, but
autoantibody specificity in patients who are homo- or heterozygous for the CFHR1 gene (n=6) was heterogeneous. No significant changes apart from total antibody titer were observed during follow-up in each patient. Fine
epitope mapping with recombinant FH SCR19-20 containing single
amino acid mutations showed significantly reduced binding in 6 out of 14 patients. In most cases,
autoantibody binding to residues 1183-1189 and 1210-1215 was impaired, revealing a major common
autoantibody epitope. Avidities showed variations between patients, but in most cases the avidity index did not change upon time. Most
autoantibodies were
IgG3, and all but three presented only with kappa or with lambda light chains. Although the pathogenic role of anti-FH
autoantibodies in aHUS is well established, this study shows
autoantibody heterogeneity among patients, but no significant variation in their characteristics over time in each patient. The presence of a single light chain in 16 out of 19 patients and the limited number of recognized
epitopes suggest a restricted
autoantibody response in most patients.