Journal
LUPUS
Volume 25, Issue 12, Pages 1328-1340Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0961203316642307
Keywords
Factor H; lupus nephritis; functions; genes; single-nucleotide polymorphisms (SNPs)
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Funding
- Chinese 973 project [2012CB517702]
- National Natural Science Foundation of China [81321064, 81470932, 81400704]
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Objective Our previous study showed that plasma levels of factor H (FH) were significantly decreased in patients with lupus nephritis and reflected lupus nephritis activity. The aim of this study was to further investigate invitro biofunctions of plasma FH in patients with lupus nephritis. Methods FH was purified from the first run of plasma exchange in four active lupus nephritis patients and two non-renal involvement systemic lupus erythematosus (SLE) patients, and plasma from two healthy controls. Then, the biofunctions of the purified FH were analyzed. In addition, FH exons sequencing analysis was performed. Results Homogeneous FH was purified from the plasma fractions and the purity of the purified FH was comparable to the commercial FH. The abilities of FH binding with C3b and mCRP, and its protecting abilities from the lysis of sheep erythrocytes, from No. 3 and No. 4 lupus nephritis patients, decreased significantly compared with those in normal controls. The purified FH from lupus nephritis patients Nos. 2-4 could not induce the phagocytosis of late apoptotic cells significantly compared with normal controls. All four lupus nephritis patients had the known SNP rs1061147 (SCR5, A307A), rs1061170 (SCR7, Y402H), CM050194 (SCR20, S1191W) and CM010322 (SCR20, V1197A), which might be associated with the above dysfunctions. Conclusions Dysfunctions of FH, including the regulations of complement alternative pathway and the clearance of apoptotic cells, were found in some active lupus nephritis patients, which were associated with their clinical phenotypes. The FH SNPs might contribute to the dysfunctions of FH in patients with lupus nephritis.
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