Association of the anti-properdin IgG with markers of disease activity
The associations between levels of anti-Properdin and proteinuria, urinary sediment and renal function were investigated.
The median level of proteinuria in anti-properdin seropositive patients was 1.56 g/24h (from 0.05 to 15.72) and the median level of proteinuria in negative for anti-Properdin antibodies patients was 0.32 g/24h (from 0.02 to 8.73). There was a trend toward that positive for anti-properdin patients had higher proteinuria than in negative ones (p=0.056, Fig. 2B) but there were no correlation between anti-properdin and proteinuria (r=0.165, p=0.170, data not shown) and between anti-properdin and eGFR (r=-0.225, p=0.059, Fig. 2C). Also, the presence of anti-properdin did not determine the presence of active urinary sediment (more than 8 erythrocytes/μl, or more than 8 leukocytes/μl, or cellular casts in non-centrifuged urine sample) (p=0.931, data not shown).
The median level of anti-Properdin antibodies in patients positive for anti-dsDNA levels – 0.232±0.292 – were higher than median level of anti-properdin in negative for anti-dsDNA patients (0.070±0.134) (p=0.013, Fig. 2E) Positive for anti-properdin and for anti-dsDNA patients were 9/14 (64.3%). Negative for anti-Properdin and negative for anti-dsDNA patients were 31/47 (66.0%). We found a trend toward an association of serological status of anti-Properdin with that of anti-dsDNA (p=0.064).
Patients with low C3 levels had higher median level of anti-properdin – 0.243±0.253 in comparison with patients with reference levels of C3 – 0.108±0.204; (p=0.008, Fig. 2F). The patients with increased anti-properdin levels and low levels of C3 were 6/14 (42.9%) and patients with reference levels of anti-properdin and C3 were 6/53 (11.3%). The presence of pathologically increased anti-properdin statistically significant determines the presence of C3 hypocomplementemia with relative risk 3.79; 95% CI: 1.44 – 9.95, р=0.013.
Moderate correlations between anti-properdin and ANA titers (r=307, p=0.020, Fig. 2I), and between anti-properdin and anti-dsDNA (r=309, p=0.017, Fig. 2J) were established. Weak and negative correlations between anti-properdin and С3 (r=-256, p=0.036, Fig. 2K) and between anti-properdin and С4 levels (r=-270, p=0.034, Fig. 2L) were found.
Positive for anti-properdin patients in category A, according BILAG Renal score were 6/21 (28.6%), in category В – were 6/24 (25.0%), in category С – 2/8 (25.0%) and in category D – 2/18 (11.1%). (Fig. 2A). Statistically significant difference in the levels of anti-properdin in different categories of BILAG Renal score has not been established (Fig. 2A).
Category A BILAG patients had a higher anti-properdin titer in comparison to patients in other BILAG categories (Fig. 2A). The significance of anti-properdin alone to identify patients in category A BILAG or in a group with other markers of LN activity was evaluated (Table 1). Anti-C1q alone and in combination with anti-dsDNA or in combination with anti-dsDNA and levels of complement C3 and C4 showed significant specificity to identify patients with A BILAG category (Table 1). Although anti-properdin alone could not be used for identification A BILAG patients (p=0.275), they in combination with anti-dsDNA could significantly increase sensitivity (70.7%) and NPV (89.8%), but decrease the specificity (57.3%) in the identification of patients in A BILAG category in comparison with anti-C1q and anti-dsDNA together (sensitivity 38.1% and specificity 91.4%, Table 1).
Comparative analysis between levels of anti-properdin in the groups of patients with and without histological signs of LN activity and chronicity were made (Table 2). High levels of anti-properdin significantly associated with renal histologic lesions, like sudendothelial immune deposits type “Wire loop” (p=0.009, Table 2), cellular (p=0.009, Table 2) and fibrous crescents (p=0.008, Table 2). A statistically significant correlation between levels of anti-properdin and histological activity and chronicity indexes did not found (r=0.175, p=0.190 and r=0.094, p=0.482, data not shown).