Introduction
The production and structure of properdin
The function of properdin in the alternative pathway of the complement system
Activation of the alternative pathway
Regulation of alternative pathway activity
The place of properdin in the alternative pathway
Properdin as a stabilizer of alternative pathway convertases
Properdin as an initiator of alternative pathway activity
Properdin in the local microenvironment
Clinical significance of properdin
Properdin deficiency
Potential role for properdin in human pathologies
Disease/condition | Findings | Reference |
---|---|---|
a. Diseases and conditions associated with reduced systemic properdin levels | ||
C3 glomerulopathy | Reduced P levels compared to controls. Average P levels were almost two times lower in C3GN compared with DDD, while sC5b-9 levels were elevated in C3GN compared with DDD. | Zhang et al. 2014 [12] |
Reduced P levels compared to controls (i.e., below the mean-2sd) in 53% of the patients negative for C3NeF. C3GN was more frequent in the C3NeF-negative group, but no difference in C3GN frequency between the groups with normal versus reduced P. P consumption correlated with reduced C3 and C5 levels, with elevated sC5b-9 levels, and with a higher degree of proteinuria. | Corvillo et al. 2016 [11] | |
Reduced P levels just below the lower limit of the reference range of controls in 4 out of 5 patients positive for C4NeF. Also decreased serum C3 and C5 levels, while C3c and sC5b-9 were increased. | Zhang et al. 2017 [13] | |
Anti-neutrophil cytoplasmic antibody-associated vasculitis | Reduced P levels in active phase versus controls and versus remission, while plasma C3a, Bb, C5a, and sC5b-9 were elevated in active stage compared to remission. P levels inversely correlated with the proportion of crescents in the renal specimen. | Gou et al. 2013 [21] |
Lupus nephritis | Approximately two-times reduced P levels in active lupus nephritis compared to controls, accompanied by increased plasma C3a, Bb, C5a, and C5b-9. | Gou et al. 2013 [21] |
Human sepsis | Reduced P levels in patients on admission to the intensive care unit compared to controls. Slightly lower P levels in non-survivors compared to survivors. Low P levels correlated to increased treatment duration. | Stover et al. 2015 [14] |
Chronic heart failure | Reduced P levels compared to controls, especially in those with a more advanced clinical disease, while FD and sC5b-9 were increased. P levels correlated with measures of cardiac function and were associated with adverse outcome. | Shahini et al. 2017 [16] |
Viral lower respiratory tract infections | Reduced P levels in patients with severe compared to mild diseasea, although no differences found in acute versus recovery samples. | Ahout et al. 2017 [96] |
Chemotherapy-induced neutropenia | Reduced P levels in the neutropenic state versus the preneutropenic state with normal neutrophil counts. | Tsyrkunou et al. 2017 [9] |
b. Diseases and conditions associated with increased properdin levels | ||
Healthy first-degree relatives of type 2 diabetes subjects | Elevated P levels in healthy first-degree relatives of type 2 diabetes subjects compared to age-matched controls. FB and sC5b-9 were also significantly higher in first-degree relatives, but no differences in C3, Bb, C3a, or FH. | Somani et al. 2012 [15] |
Hemodialysis | Elevated P levels (by approximately factor 1.3) compared to controls, and slightly higher levels at the end of the hemodialysis session compared to the start. Also increased levels of C3d and C5b-9 after hemodialysis. | Poppelaars et al. 2016 [18] |
Antibody-mediated rejection in heart transplant recipients | Elevated P levels in AMR patients carrying a rare AMR-associated allele in the P gene compared to control patients not carrying the rare allele and without AMR. | Marrón-Liñares et al. 2017 [97] |
Cardiovascular events | Elevated P levels were associated with endothelial dysfunction, and with the risk of cardiovascular events. | Hertle et al. 2016 [98] |
IgA nephropathy | Elevated P levels (by approximately factor 1.5) compared to controls. Also in the patients followed over time, P levels remained higher. | Onda et al. 2007 [22] |
Studies of properdin-deficient mouse models
The role of properdin in complement-mediated renal injury
C3 glomerulopathy
Clinical manifestation and pathogenesis
Unexpected findings of properdin gene knockout in C3G
Possible role for properdin in the distinction of C3G subgroups with different pathophysiology
Type of C3NeF | Properdin-independent C3NeF | Properdin-dependent C3NeF/C5NeF |
Associated complement profile | C3 consumption | C3 consumption |
C5 normal or slightly consumed | C5 consumption | |
sC5b-9 normal | sC5b-9 elevated | |
Disease association | DDD | C3GN |
Comparative mouse model | FH−/−/P−/− | FH−/− |