Association of serum C3 levels with the risk of myocardial infarction.

PURPOSE: Serum complement and IgA levels have been found to be retrospectively associated with the presence of diffuse atherosclerosis. This study was performed to assess whether serum immunoglobulins and complement components are predictive of future ischemic events. PATIENTS AND METHODS: The baseline values of IgG, IgA, IgM, C3, and C4 were measured in the sera from a cohort of 860 inhabitants of the town of Brisighella, Italy. They were 444 men and 416 women, mean age 53.9 years (SD 12.4, range 23 to 84), who had not had any ischemic events (myocardial infarction [MI], angina pectoris, stroke, transient ischemic attack, or intermittent claudication) at the time of blood sampling in 1984. Their baseline values for the main recognized risk factors for atherosclerosis were known at baseline and for 4 years of follow-up. Multiple logistic regression analysis was performed for associations between ischemic events and immunologic variables (including serum IgG, IgA, IgM, C3, and C4) and risk factors for atherosclerosis (including age, sex, diastolic blood pressure, cigarette consumption, Quetelet index, total cholesterol, HDL cholesterol, triglycerides and blood glucose). RESULTS: During follow-up, 57 subjects experienced ischemic events, including 28 cases of coronary heart disease (17 MI and 11 angina pectoris). Of the immunologic variables studied, only serum C3 was found to be independently associated with ischemic events (P < 0.005 for any ischemic events, coronary heart disease, and MI). The population was divided into thirds according to C3 values. The cumulative incidence of MI was 7.1/1,000 in the low third, 10.6/1,000 in the middle third and 40.8/1,000 in the high third (risk ratio for high versus middle plus low = 4.2 after adjustment for age and sex; 95% CI 1.5 to 11.7). A separate analysis for the sexes showed that serum C3 was a particularly powerful predictor of MI in men. Men whose C3 levels were in the top third had a 72.6/1,000 incidence of MI while the incidence in the rest of the male population was 6.2/1,000 (risk ratio 10.7 after adjustment for age; 95% CI 2.3 to 49.0). When similar analyses were performed for angina pectoris, stroke, and intermittent claudication, no significant increase in risk was found to be associated with serum C3. CONCLUSION: C3 levels measured in sera from male subjects without previous ischemic events are independently associated with the risk of MI.

Increased serum IgA levels in subjects with previous myocardial infarction or other major ischemic events.

To ascertain whether the increase in serum IgA, which has been found to be associated with the presence of severe atherosclerotic disease, precedes or follows the occurrence of major ischemic events (MIE), we studied the serum levels of IgA as well as IgG and IgM in 145 subjects with acute or previous ischemic events and 34 controls. The subjects with previous myocardial infarction had higher IgA levels with respect to the controls, the patients with angina pectoris and those with acute myocardial infarction, while no significant differences concerning IgG and IgM were found. In the subjects with previous extracoronary events, immunoglobulin levels tended to be even higher. Overall, 30% of the subjects with previous MIE and only 3% of the controls had IgA levels over 4.5 g/l (p = 0.0018). This study indicates that total serum IgA is a marker of previous major ischemic events (protracted immune response to denatured proteins?), rather than a factor predisposing to atherosclerosis development.

[Association of serum C3 and essential hypertension]. / Associazione fra C3 sierico e ipertensione essenziale.

This study was performed to assess the possible involvement of humoral immunity in essential hypertension, independently of the presence of atherosclerotic disease, which in turn may be associated with immunologic changes. Sixty-five patients without demonstrated atherosclerotic disease were selected according to clinical and arteriographic criteria, including 23 hypertensive subjects (all pharmacologically treated) and 42 controls. Mean ages (58.7 +/- 8.3(1 S.D.) years in the controls and 57.7 +/- 7.9 years in the hypertensive subjects) and sex distribution were similar in the 2 groups. Of the main risk factors, atherosclerosis, smoking, diabetes, total cholesterol and HDL-cholesterol were equivalent, while triglycerides were higher in the hypertensive subjects than in the controls (142.6 +/- 52.7 vs. 112.6 +/- 67.7 mg/dl; p = 0.0065). In these subjects' sera the immunoglobulins IgG, IgA and IgM, and the third and fourth complement components (C3 and C4) were measured. Of these variables, only C3 was higher in the hypertensive subjects than in the controls (124.3 +/- 29.3 vs. 107.8 +/- 18.4 mg/dl; p = 0.0183). Furthermore, C3 was significantly correlated with triglycerides (tau = 0.3613; p < 0.0001), but the association with hypertension was confirmed only for C3, and not for triglycerides, by multiple logistic regression (p = 0.0142). The increase in serum C3 suggests the possible implication of humoral immunity in the pathogenesis or progression of essential hypertension.

[Increased serum levels of IgA and C4 in atherosclerosis: the absence of a correlation with the arteriographic picture]. / Incremento dei livelli sierici di IgA e C4 nell'aterosclerosi: assenza di correlazione con il quadro arteriografico.

We have previously shown that an increase in serum IgA and C4 is often detectable in presence of diffuse atherosclerotic disease. The present study was performed to verify such results in a different and larger sample of subjects, and to ascertain whether the above immunologic variables are correlated with the severity of atherosclerotic disease. Seventy-three atherosclerotic subjects with at least 1 significant (> 75%) stenosis in a major arterial branch were selected according to the reports of arterial panangiographies performed previously. Among them, 36 subjects (24 men and 12 women, mean age 63 +/- 7 years) were singled out, who matched by age and sex 36 control subjects (mean age 63 +/- 7 years). In all of these subjects the following serum immunologic and lipid variables were measured: IgG, IgA, IgM, IgE, C3, C4, total cholesterol, HDL-cholesterol and triglycerides. With respect to the controls, the 36 matched atherosclerotic subjects had higher levels of IgA (263.0 +/- 119.8 vs 334.3 +/- 130.5 mg/dl; p = 0.0126), C4 (25.7 +/- 5.8 vs 30.4 +/- 9.1 mg/dl; p = 0.0297) and triglycerides (153.1 +/- 77.3 vs 209.7 +/- 141.3; p = 0.0500). No correlation was found between the number of arterial stenoses (range 1-8, mean 2.9 +/- 1.5) and any of the immunologic or lipid parameters in all the 73 atherosclerotic subjects. Only the daily cigarette consumption was correlated with the disease extension (tau = 0.1984; p = 0.0392).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations between serum lipids and complement components in adults without demonstrated atherosclerotic disease.

The variability due to age and sex and the reciprocal relations of serum IgG, IgA, IgM, C3, C4, total cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG) were studied in 87 subjects (46 men and 41 women, aged 20-75 years) selected for the absence of significant atherosclerotic lesions. Serum IgA and C3 were higher in men than in women (P less than 0.05) mainly in the age group 41-60, while IgM and HDL-C were higher in women than in men (P less than 0.05 and P less than 0.01, respectively), especially in the age group 20-40. Direct univariate correlations with age were found for serum TC (P less than 0.0001), IgA (P less than 0.001), and C4 (P less than 0.01) but the latter correlations was confirmed only in women by multivariate analysis. These 3 variables had the major increment in the age group 41-60 in men, while in women the increase associated with age was more progressive or late. Univariate analysis showed a 'ring' of highly significant correlations (P less than 0.0001) involving serum lipids and complement components (TC-C4-C3-TG-TC). The correlation between TC and C4 was present only in men in multivariate analysis and improved with increasing age. These findings might represent a clue to explain the previously reported association between serum C4 and atherosclerosis.

Peritoneal equilibration curve for beta-2-microglobulin (B2M) in CAPD patients.

To evaluate B2M removal during CAPD, the equilibration curve was determined in 9 CAPD patients (aged 67.9 +/- 6.5 years, treated for 19.0 +/- 17.4 months). The study was carried out on 2 consecutive days using 1.36% (day 1) and 3.86% (day 2) dextrose dialysis solutions for 6 hours each day. The B2M plasma value was the mean of 4 samples taken at the start and after 2, 4 and 6 hours. Dialysate values were determined on 3 ml samples taken every 30 minutes. The curve was fitted for dialysate to plasma B2M ratio (D/P) versus time to define the B2M equilibration curve. Our results showed that the value had a linear regression with both types of solution in all patients. The D/P B2M ratio was linear during the 6 hours of dwell time. Furthermore, there was no significant difference between the 2 solutions used. In conclusion, standard CAPD allows a low but constant B2M removal. An increase or a reduction in dwell time do not seem to have any influence on the B2M removal, which could be improved by methods other than varying dwell time and/or solution osmolarity.

Association of serum IgA and C4 with severe atherosclerosis.

To assess the possible involvement of humoral immunity in diffuse atherosclerosis, IgG, IgA, IgM, C3 and C4 were measured in the sera of 23 atherosclerotic subjects (at least 3 stenoses greater than 75% in the arteries of the limbs and neck, as assessed by panangiography) and of 20 controls (possible stenoses less than 40% documented by arteriography of the aortic arch and epi-aortic branches and "normal" response to exercise stress testing and Doppler ultrasonography of the arteries of the lower limbs). Age (59-69) and sex distribution did not differ significantly in the 2 groups. The following serum concentrations were higher in the atherosclerotic subjects than in the controls: C4 (28.7 +/- 6.5 (1 SD) vs. 23.4 +/- 3.8 mg/dl; P = 0.0013); IgA (323.3 +/- 155.0 vs. 210.3 +/- 87.9 mg/dl; P = 0.0020); and C3 (126.3 +/- 16.9 vs. 111.0 +/- 18.9 mg/dl; P = 0.0109). To assess whether these parameters were independently associated with atherosclerosis, a multiple logistic regression was performed, also including other variables which differed between the atherosclerotic group and the control group with P values less than 0.20 (cigarette smoking, arterial hypertension, body mass index, serum HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, serum triglycerides, IgG and IgM). In multivariate analysis only IgA (P = 0.0012), C4 (P = 0.0072), cigarette smoking (P = 0.0141) and serum triglycerides (P = 0.0177) were independently associated with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma exchange therapy in rapidly progressive renal failure due to multiple myeloma.

Nineteen patients with severe renal failure due to multiple myeloma and with Bence Jones proteinuria greater than 1 gm/day were randomly assigned to group I or group II. Corticosteroids and cytotoxic drugs were given to all cases. The 9 patients of group I were also treated by peritoneal dialysis and the 10 patients of group II by plasma exchange and hemodialysis. Only 1 patient of group I, who was not oliguric at the onset, showed partial recovery from renal failure after 3 months of therapy, while 9 patients of group II (3 of whom were oliguric) had significant decrease in Bence Jones proteinuria and rapid improvement from the renal failure. In our experience, plasma exchange is more effective than peritoneal dialysis for reducing Bence Jones proteinuria and recovering from renal failure, even when there is oliguria.

[Fluorometric method for the assay of IgG produced in lymphocyte cultures]. / Metodo fluorimetrico per la valutazione delle IgG prodotte nelle colture linfocitarie.

We have studied the IgG secreted in a system of CML. Microquantity of IgG (30-3000 micrograms/ml) of culture was determined using a fluorometric method based on the determination of the fluorescence derived by immune-complex IgG-FITC labeled goat Anti-human antibody to IgG covalently coupled to hydrophilic beads. This techniques has showed a good sensibility and accuracy.