Case report: A transplant candidate with unexpected serum reactivity against the 45KE eplet on HLA-B alleles.

This case report describes the serum antibody specificity against the 45KE eplet which had not been yet shown to be antibody-verified. This antibody was produced by a 41-year-old European male with Berger's disease. His serum had HLA class I antibody reactivity as determined in IgG binding assays with single allele panels (OneLambda, ThermoFisher, Lot 8 and Lot 9). The HLAMatchmaker analysis revealed reproducible serum reactivity only with alleles carrying the 45KE eplet. The cause of this 45KE-specific immunization is unknown because this male patient had never been transfused nor received a previous transplant, Moreover, his mother's HLA type did not have any 45KE-carrying allele. This finding might be related to observations reported in the literature about the appearance of HLA-reactive antibodies following influenza vaccination but this possibility could not be investigated.

The changes in NT-proBNP plasma concentrations during dialysis are highly dependent of the dialysis membrane ultrafiltration coefficient.

BACKGROUND: NT-proBNP is a powerful marker with diagnostic and pronostic value for heart failure. It is of particular interest in patients with end-stage renal disease who are at high risk for heart failure. The aim of this study was to investigate the effect of hemodialysis on plasma NT-proBNP concentrations. METHODS: NT-proBNP concentration was measured in 67 patients before and after hemodialysis. RESULTS: In the 20 patients dialyzed with a membrane whose ultrafiltration coefficient was below or equal to12, NT-proBNP concentration was comparable after and before dialysis (16611+/-21024 vs. 15216+/-19027 pg/ml, NS). At the opposite, in the 47 patients dialyzed with a membrane whose ultrafiltration coefficient was above or equal to 40, NT proBNP concentration was 35% lower after dialysis compared to before dialysis (11983+/-21819 vs. 18574+/-31862 pg/ml, p<0.0001). CONCLUSIONS: In patients dialyzed with a membrane whose ultrafiltration coefficient is high, dialysis is likely to decrease results by one third. Thus sampling blood before dialysis in hemodialyzed patients appears as the best time to stratify the cardiovascular risk in these patients.

Adiponectin is an important determinant of apoA-I catabolism.

OBJECTIVE: Plasma concentration of adiponectin is positively correlated with high-density lipoprotein (HDL) cholesterol level. However, the role of adiponectin on HDL metabolism remains unknown. This prompted us to perform an in vivo kinetic study of apoA-I, the main apolipoprotein of HDL, using stable isotopes, in 22 subjects with a wide range of plasma adiponectin, including 11 patients with metabolic syndrome (8 with type 2 diabetes, 3 without type 2 diabetes) and 11 normal individuals. METHODS AND RESULTS: In the 22 studied subjects, plasma adiponectin levels ranged from 2.57 to 14.44 microg/mL and apoA-I fractional catabolic rate (FCR) values ranged from 0.142 to 0.340 day(-1). A strong negative correlation was found between adiponectin and apoA-I FCR (r=-0.66, P<0.001) in the whole studied population and, to a similar extent, in patients with metabolic syndrome (r=-0.73, P=0.010) and normal subjects (r=-0.68, P=0.020), separately. In multivariable analysis, apoA-I FCR was associated negatively with adiponectin (P=0.005) and positively with HDL triglycerides/cholesterol ratio (P=0.006), but not with age, sex, body mass index (BMI), waist circumference, plasma triglycerides, HDL cholesterol, fasting glycemia, and QUICKI. Both adiponectin and HDL triglycerides/cholesterol ratio explained 62% of the variance of apoA-I FCR and adiponectin on its own explained 43%. CONCLUSIONS: Our kinetic study shows a strong negative correlation between adiponectin and apoA-I FCR, which can explain the positive link between HDL cholesterol and adiponectin. This association is independent of obesity, insulin resistance, and the content of triglycerides within HDL particles. These data suggest that adiponectin may have a direct role on HDL catabolism.

Changes in apolipoprotein B100-containing lipoprotein metabolism due to an estrogen plus progestin oral contraceptive: a stable isotope kinetic study.

CONTEXT: Oral contraceptives with estrogen plus progestin are likely to influence apolipoprotein B (apoB)-containing lipoprotein metabolism by changing the expression of different enzymes or receptors that play a major role in this metabolism. However, the precise changes in apoB kinetic parameters induced by oral contraceptives that are now currently used are unknown. OBJECTIVES: We studied the impact of Moneva, containing 30 microg ethinylestradiol and 75 microg gestodene, on the apoB production rate and fractional catabolic rate of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL). DESIGN: Using a 16-h [(13)C]leucine infusion, we performed an apoB kinetic study in nine normolipidemic women before and 3 months after beginning Moneva. RESULTS: On Moneva, serum triglycerides increased moderately (+12%, P = 0.04) in the fed state, whereas serum LDL remained unchanged. LDL particles were richer in triglycerides in women on Moneva (7.5 +/- 1.5 vs. 4.3 +/- 1.0% of total LDL mass, P < 0.01). The apoB production rate of VLDL, IDL, and LDL increased by 49 (P = 0.04), 55 (P = 0.05), and 51% (P = 0.01), respectively. The fractional catabolic rate of apoB in LDL increased by 36% (P = 0.04). Consequently, the serum LDL apoB pool size remained unchanged (26.49 +/- 6.98 vs. 23.96 +/- 5.37 mg/kg). CONCLUSION: Oral contraception with ethinylestradiol plus gestodene induces an increase in the production rate of apoB-containing lipoproteins all along the VLDL-->IDL-->LDL cascade. The increased production rate of apoB in LDL is counterbalanced by a higher fractional catabolic rate of apoB in LDL, thus precluding an increase in the concentration of atherogenic LDL particles.

Detection of plasma cells, C4d deposits and donor-specific antibodies on sequential graft biopsies of renal transplant recipients with chronic dysfunction.

BACKGROUND: In order to look for a relationship between humoral mechanisms of rejection and chronic allograft dysfunction, plasma cells, C4d deposits and donor-specific antibodies (DSA) were simultaneously sought on serial biopsies of kidney allograft recipients. PATIENTS AND METHODS: Ten recipients with chronic dysfunction (G1) and 8 recipients with long-term normal graft function (G2) were included. Biopsies and serums were sampled at early graft dysfunction (T1), between 8months and 2years (T2) and after the third year following transplantation (T3). RESULTS: In G1, plasma cells represented 12.3% (T1), 8.2% (T2) and 14.1% (T3) of mononuclear cells. The mean percentage of plasma cells was 11.6% in G1 versus 0.4% in G2 (p<0.05). A progressive rise in C4d deposits was seen in G1, from 25% at T1 to 80% at T3. Donor-specific antibodies were identified in at least one serum sample of 60% of the patients in G1 and 12.5% of the patients in G2 (p=0.012), whereas donor-specific antibodies were eluted from at least one biopsy of 50% of the patients in G1 and 12.5% of the patients in G2 (p=0.03). In G1, C4d deposits were significantly associated with plasma cells (p=0.0012) and anti-HLA Abs in serum samples and/or eluates (p=0.026). CONCLUSION: This study shows that plasma cells, DSA and C4d are associated in renal transplants developing chronic rejection.

Increased apolipoprotein AI production rate and redistribution of high-density lipoprotein size induced by estrogen plus progestin as oral contraceptive.

CONTEXT: The impact of estrogen plus progestin as an oral contraceptive on high density lipoprotein (HDL) apolipoprotein (apo) AI metabolism in humans is poorly understood. OBJECTIVES: This study was designed to measure the in vivo effect of Moneva (30 microg ethinylestradiol, 75 microg gestodene) on HDL apoAI production rate and fractional catabolic rate. DESIGN: Using (13)C-leucine, we performed two kinetic studies in the fed state in 10 normolipidemic young women, before and 3 months after beginning Moneva. RESULTS: On Moneva, serum triglycerides increased by 12% (P = 0.03) in the fed state, whereas low-density lipoprotein and HDL cholesterol remained unchanged. HDL apoAI pool size and production rate were increased by 9.2% (67.3 +/- 7.1 vs. 61.6 +/- 6.7 mg x kg(-1); P = 0.05) and 26.5% (14.3 +/- 2.7 vs. 11.3 +/- 2.2 mg x kg(-1) x d(-1); P = 0.02), respectively. HDL apoAI fractional catabolic rate was not significantly modified. Three-month treatment by Moneva induced a shift of HDL size distribution from HDL2 toward HDL3 (HDL3 = 51.5 +/- 8.1 vs. 46.5 +/- 9.2% of total HDL; P = 0.02) and an increase in the proportion of apoAI among HDL components (38.8 +/- 4.3 vs. 34.4 +/- 2.8%; P = 0.01). CONCLUSION: Oral contraception by estrogen plus progestin induces changes in HDL apoAI metabolism characterized by an increase in production rate and pool size, with a higher proportion of HDL3 particles. Whether or not these changes are beneficial to prevent atherosclerosis has to be explored further.

Molecular characterization of isolates of waterborne Cryptosporidium spp. collected during an outbreak of gastroenteritis in South Burgundy, France.

In September 2001, a waterborne outbreak of gastroenteritis occurred in eastern France. Of 31 fecal samples from symptomatic individuals, 19 tested positive for Cryptosporidium with two PCRs targeting the Hsp70 and the 18S rRNA genes of CRYPTOSPORIDIUM: Sequencing of the PCR fragments produced sequences identical to that of Cryptosporidium parvum genotype 1.