Albert Tacquet

Evolution Pattern of Auto-Antibodies against Oxidized Low-Density Lipoproteins in Renal Transplant Recipients

An increased degree of oxidative stress in renal transplant recipients and a possible role of ciclosporin A (Cs-A) immunosuppressive therapy in this process have already been described. However, prospective data using in vivo markers and the influence of Cs-A in the oxidizability of low-density lipoprotein (LDL) are scarce. We aimed at investigating in this prospective study the evolution pattern of auto-antibodies directed against malondialdehyde-modified LDL (MDA-LDL) and Cu2+-oxidized LDL in 28 stable renal transplant recipients on Cs-A immunosuppressive therapy before and after 3 successive years of renal transplantation. Also, the effect of enrichment of LDL with Cs-A on the susceptibility of LDL to in vitro oxidation was tested. The results showed a significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL) after 1 year, and the values remained high during the 2nd and the 3rd year following transplantation. The yearly mean relative variations of auto-antibodies against MDA-LDL and Cu2+-oxidized LDL during the follow-up period were 133, 149, and 137%, and 111, 115, and 117%, respectively. A significant correlation was observed during the 1st year between Cs-A trough blood level and Cu2+-oxidized LDL auto-antibody: r = 0.04 (p = 0.046). Incorporation of Cs-A into LDL from healthy volunteers showed no changes during the lag phase in comparison with Cs-A-free LDL, indicating that Cs-A had no effect on in vitro LDL oxidizability. Our results suggest that Cs-A may be involved earlier in the LDL oxidation, but the mechanism by which it acts is still unclear.

Apo(a) phenotypes and Lp(a) concentrations in renal transplant patients

Plasma lipoprotein (a) (LP(a)) concentrations are increased in patients with end-stage renal disease. Considering the influence of the apolipoprotein (a) (Apo(a)) polymorphism and the mode of dialysis in this prospective longitudinal study, we compared Lp(a) concentrations before and after the first 6 months of a successful kidney transplantation in 125 recipient patients. Apo(a) phenotyping was performed by using SDS-PAGE and SDS-agarose, isoforms were classified into high molecular weight (HMW) and low molecular weight (LMW). Before the graft, the Lp(a) concentrations were significantly higher in CAPD than in hemodialysis patients (p = 0.021). Six months after transplantation, Lp(a) fell in both treatment groups. This decrease occurred within both LMW and HMW but to a different extent: median relative variations were –35 and –50%, respectively (p = 0.048). Among patients with Lp(a) concentration >30 mg/dl 6 months after transplantation, 74% had LMW Apo(a) isoform while the remaining 26% had HMW isoform. Successful renal transplantation leads rapidly to a correction of Lp(a) concentrations, especially in patients treated with CAPD who have higher Lp(a) levels. The most important factor seems to be the LMW status corresponding to high Lp(a) levels.

Lipoprotein particles in homozygous familial hypercholesterolemic patients treated with portacaval shunt and LDL apheresis

Lipoprotein particles containing apolipoproteins (Apo) were studied by enzyme-linked-immunosorbent assay in two homozygous familial hypercholesterolemic patients (1 male and 1 female) with portacaval shunts, and in controls. Total Apo B, total cholesterol and LDL cholesterol were increased in both patients while complex Apo B containing particles, Lp CIII: B, were not increased in these FH patients. The dextran-sulfate cellulose columns (Liposorber LA-40) had an excellent adsorption selectivity and adsorption capacity for lipoprotein particles containing Apo B and a minimum adsorption capacity in Apo AI and Apo AII-containing particles. This apheresis technique selectively depleted plasma of atherogenic Apo B-containing particles with a minimal loss of antiatherogenic Apo AI-containing particles.

Apolipoprotein Al and Apolipoprotein B Containing Particle Analysis in Normolipidemic Hemodialyzed Patients: Evidence of Free Apolipoprotein E

Whole plasma from 6 normolipidemic chronic renal failure (CRF) patients undergoing hemodialysis treatment was passed through the anti-apolipoprotein (Apo) AI immunosorbent column connected to the anti-Apo B immunoaffinity column. Apo AI and B containing particles were analyzed for lipid and Apo contents. The results were compared with findings obtained in age-matched normolipidemic healthy controls. Although plasma Apo AI and AII levels decreased in CRF patients, the concentrations of Apo CII, CIII, and E coeluted with Apo AI were similar to those of the controls. The slightly elevated plasma concentrations of Apo CII and CIII in the CRF patients studied were shown to be associated with Apo B containing particles. The nonretained fraction from both groups contains no Apo AI and no Apo B, but still contains lipids and other Apo such as Apo AII and Apo CII. The occurrence of approximately 29% of plasma Apo E in this fraction constitutes the main abnormality found in these patients (< 5% in controls). A two-phase electroimmunoassay shows that this Apo E did not correspond to the plasma E-AII complex. These findings show that the compositional alterations of Apo AI and Apo B containing particles in CRF patients were observed even in normolipidemic patients and suggest that the kidney may play a metabolic role in the removal of free forms of lipoprotein particles such as free Apo E.

Apolipoprotein B immunochemical heterogeneity in dialysed patients with chronic renal failure and patients with coronary artery stenosis.

Serum cholesterol, triglyceride, apolipoprotein B (apo B) and the cholesterol and phospholipid content of apo-B-containing particles was determined in 41 male patients on dialysis for chronic renal failure, in 41 male patients with coronary artery disease selected on the basis of a total cholesterol level below 6.72 mmol/l and in 41 male control subjects of similar age. Apo B was assessed as total B protein determined using polyclonal antibodies and also by measuring the expression of epitopes recognized by three different monoclonal antibodies (BL3, BL5 and BL7). Triglyceride was increased (p less than 0.01) and cholesterol was decreased (p less than 0.01) in the dialysed patients with chronic renal failure. Total apo B was similar in the three tested groups while the expression of the BL7 epitope was increased in the group of dialysed patients with chronic renal failure (p less than 0.001). The expression of BL3 and BL5 epitopes was increased in patients with coronary artery disease (BL3: p less than 0.05; BL5: p less than 0.02) but not in dialysed patients with chronic renal failure. These results suggest an abnormal composition and an immunological heterogeneity of apo-B-containing lipoprotein particles in patients with coronary artery stenosis and in dialysed patients with chronic renal failure.

Metabolic Effects of Theophylline

Excerpt To the editor: Kearney and colleagues (1) state that toxic levels of theophylline were associated with hypokalemia, hyperglycemia, and metabolic acidosis in a patient and in four anesthetiz...

Étude des glycoprotéines du sérum de cobaye soumis à l'empoussiérage pulmonaire et à l'infection mycobactérienne

Abstract Guinea pigs have been submitted to pulmonary aggressions: infection by Mycobacterium kansasii , injected intra-venously,—“dust” inhalation during 18 days, 6 hours per day,—infection followed by dust inhalation,—and dust inhalation followed by infection. The augmentation of blood serum glycoproteins is important only when guinea pigs have been submitted successively to infection and dust inhalation. The modified fractions are essentially the group of perchloro-soluble seromucoids; the same modifications have been detected in pulmonary and renal tissues.