Fig. 5: Antibody-mediated complement activation increases ATTR phagocytosis and tissue amyloid clearance.

a In vitro ATTR phagocytosis assay performed with human-derived macrophages, TTR-L55P-atto488, and NI301A in the presence of fresh or heat-inactivated human plasma at different concentrations (mean ± SD of quadruplicates). b Ex vivo tissue amyloid-removal assay performed with three concentrations of fresh human plasma. b₁ Representative pairs of adjacent tissue sections treated with NI301A or vehicle. b₂ Quantification of number and area of amyloid deposits per tissue section. n = 5–6 sections per condition (mean ± SD). Two-way ANOVA for main factors Plasma concentration and Antibody, and Bonferroni’s multiple comparisons test of NI301A to vehicle conditions (mean difference and 95% CI). For the number of ATTR deposits: Plasma concentration: F(2,26) = 16.04, P < 0.0001; Antibody: F(1,26) = 84.53, P < 0.0001; NI301A vs. Vehicle using 0.8% plasma: −309.4 (−461.5 to −157.3), ***P < 0.0001; NI301A vs. Vehicle using 2.4% plasma: −302.6 (−454.7 to −150.5), ***P < 0.0001; NI301A vs. Vehicle using 7.2% plasma: −308 (−446.9 to −169.1), ***P < 0.0001; NI301A vs. Isotype using 7.2% plasma: −238.3 (−367.7 to −109.0), ***P = 0.0007. For total deposit area: plasma concentration: F(2,26) = 6.85, P = 0.0041; Antibody: F(1,26) = 26.56, P < 0.0001; NI301A vs. Vehicle using 2.4% plasma: −522,593 (−899,939 to −145,246), **P = 0.0046; NI301A vs. Vehicle using 7.2% plasma: −497,895 (−842,364 to −153,427), **P = 0.0031; NI301A vs. Isotype using 7.2% plasma: −398,001 (−734,405 to −61,596), *P = 0.02. c In vitro complement activation assay of NI301A in fresh human plasma using coated ATTRwt fibrils or bovine serum albumine (BSA) as target, followed by immunodetection of the complement activation product C5b9 (mean of duplicates).