Deterioration of Immune Complex Solubilization Activity of Serum by Increased Concentration of Factor D

Abstract

We investigated the effect of excess complement factor D on the immune complex solubilization activity (ICSA) of serum. First, we estimated the concentration of factor D, ICSA and the hemolytic activity via the classical complement pathway (CH50) in the sera of 16 healthy individuals and 36 patients on hemodialysis for end-stage renal failure. The serum concentration of factor D in these patients (mean ± SD: 12.12 ± 2.38 μg/ml) was significantly higher (p < 0.001) than that in the healthy subjects (1.02 ± 0.11 μg/ml). In this study, peroxidase and antiperoxidase rabbit IgG were used as immune precipitates for ICSA. The ICSA in patients (45.8 ± 7.4 normal human serum %, NHS%) was significantly lower (p < 0.001) than that in the healthy subjects (100.2 ± 12.5 NHS%). There was no difference in CH50 between the sera of the patients (31.8 ± 2.5) and that of the healthy group (32.4 ± 2.6). Second, we determined that increasing amounts of purified factor D added to fresh serum resulted in a decrease in ICSA. This occurred in the serum of a healthy individual as well as in that of a patient. CH50 did not change regardless of the concentration of factor D used. There was an increase in C3 conversion in the sera to which purified factor D had been added, as observed by crossed immunoelectrophoresis. It is suggested that ICSA had deteriorated due to the excess of factor D, which had activated the alternative pathway of complement.

Serum Levels of the Soluble lnterleukin-2 Receptor Are Dependent on the Kidney Function

“…It is a serine protease participating in the formation of C3 convertase by cleaving factor B or C3 proactivator in the alternative pathway [19]. There is no immunological pro cess per se that causes an increase in factor D. On the other hand, it has recently been observed that an excess of factor D may cause deterioration of immune complex solubiliza tion [20], as well as disturbances of hemolytic activity [21], Increased serum concentrations of factor D in patients with reduced kidney function was originally described in 1985 [22], It is a general opinion that serum creatinine does not reflect glomerular Filtration rate from an optimal point of view. However, serum concentrations of low molecular weight proteins are reliable markers for estimat ing kidney function, for instance (^-microglobulin, vita min A transporting protein and cystatin C [23][24][25].…”

Evaluation of the Proteolytic Activity of Factor D Accumulated as an Active Serine Protease in Patients with Chronic Renal Failure

“…Other substrates were hydro lyzed much less effectively by factor D. These results indi cated that factor D, even at high concentrations such as those in patients with chronic renal failure, has almost no proteolytic activity on substrates other than its natural sub strate, factor B. Therefore, the factor D accumulated by patients with chronic renal failure seems unlikely to act directly on plasma a nd/or tissue proteins as a potent prote olytic factor in the circulation except possibly to cause imbalanced activation of the complement system [5,[10][11][12], An increased level of factor D is reported to cause detrimental modifications of the complement system in patients receiving regular hemodialysis, by activating the alternative complement pathway [5,10,12] and by decreas ing immune complex clearance [11]. Therefore, an effective method for inhibiting this proteolytic activity of factor D in the complement system should have beneficial effects.…”

“…Therefore, the accumulation of factor D may be an important detrimental factor in chronic renal failure. Previously, we and others demonstrated some pathological significance of factor D in chronic renal failure [10][11][12]. However, previous reports were on the pathological role of the complement system, and there is only one report that demonstrated the proteolytic effect of factor D on body proteins other than complement proteins [13].…”

“…In addition, we examined the effects of some synthetic serine protease inhibitors of factor D with a view to their possible clinical use, because the harmful effect of excess factor D in chronic renal failure has been suggested [4,5,10,11].…”