Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: predictive value for renal flares.

Clinical difficulties in predicting systemic lupus erythematosus (SLE) renal flares are still encountered. Biological markers such as autoantibodies (aAbs) may be of major interest for clinicians in the follow-up of SLE patients. The aim of our study was to investigate the clinical utility of one of these biological markers, anti-C1q aAbs, in predicting renal flares of SLE nephritis in comparison with the 'gold standard' anti-double stranded DNA (anti-dsDNA) aAbs. Anti-C1q aAbs and anti-dsDNA aAbs were analysed through a longitudinal retrospective study of 23 SLE patients presenting with one or more renal flares. Anti-C1q and/or anti-dsDNA aAbs were found in 20 (87%) of 23 patients, of whom 16 (69%) displayed both. Thirty-three renal flares occurred during the course of the study, and anti-C1q aAbs and anti-dsDNA aAbs were positive in 25 (76%) and 24 (73%) of these flares respectively. The sensitivity of anti-C1q and/or anti-dsDNA aAbs in predicting renal flares reached 85%. The specificity of anti-C1q aAbs was 84%, of anti-dsDNA aAbs 77% and of both aAbs 97%. Positive and negative predictive values were as follows: 56% and 70% for anti-C1q aAbs, 53% and 72% for anti-dsDNA aAbs. The combination of both aAbs had the highest positive predictive value (69%), whereas absence of both aAbs was associated with the highest negative predictive value (74%). In conclusion, our results confirm that anti-C1q aAbs are present in a significant percentage of SLE patients with active renal involvement, suggesting that these aAbs could be a useful additional marker. The presence of anti-C1q and anti-dsDNA aAbs was associated with a high risk of renal flare, whereas the absence of both aAbs excluded such an event. These data confirm that systematic detection of anti-C1q and anti-dsDNA aAbs is of interest for the follow-up in SLE patients with renal involvement.

Tumor necrosis factor alpha release is a major biological event associated with rituximab treatment.

INTRODUCTION: In patients with low-grade non-Hodgkin's lymphoma, rituximab (MabThera) produces infusion-related toxicity, including fever, rigors, and chills in greater than 50% of those treated. The majority of these reactions are grade 1 or 2. MATERIALS AND METHODS: In the GELA study LNH98-5, a total of 400 elderly patients with previously untreated diffuse large B-cell lymphoma were randomized to treatment with CHOP or with rituximab plus CHOP (R-CHOP). In a detailed investigation of biological events which may be associated with adverse reactions specific to rituximab infusion, a subgroup of 55 patients (26 in the CHOP group and 29 in the R-CHOP group) were selected for measurement of several biological parameters at baseline and at 1, 4 and 8 h (H1, H4 and H8, respectively) after commencing therapy. For 27 patients, measurements included cytokine and complement levels. RESULTS: Baseline demographic and disease characteristics were similar for patients in both treatment groups. Compared with the CHOP treatment group, patients in the R-CHOP group had significantly higher post-treatment changes in neutrophil, lymphocyte, and monocyte counts, LDH levels, C3a levels, and TNF-alpha levels. In the R-CHOP group, neutrophil levels increased at H4 (P<0.05), lymphocyte levels decreased at H1 (P<0.05), H4 (P<0.001) and H8 (P<0.05), monocytes levels decreased at H1 (P<0.01), LDH levels increased at H4 (P<0.05) and H8 (P<0.01), and C3a decreased at H1 (P<0.01). The most statistically significant changes were observed for TNF-alpha levels: Mean values of TNF-alpha increased more than 250% at H1 and H4 and were still increased by 170% at H8 (P<0.001 at all timepoints). Since only six of the 55 evaluated patients had severe adverse events, it was not possible to correlate severe toxicity with these biological variations. CONCLUSION: This analysis demonstrates that rituximab infusion was rapidly followed by activation of complement, B-lymphocyte cytolysis, and TNF-alpha release.

Brain membrane sensitivity to ethanol during development of functional tolerance to ethanol in rats.

Adult male rats were rendered progressively tolerant to ethanol by daily intragastric administration of doses of 3-6 g/kg body weight. Functional tolerance assessed by the hypothermic effect after injection of a challenge dose of ethanol developed slowly and was demonstrable after 2 weeks of treatment. Intrinsic crude synaptosomal membrane fluidity, as assessed by fluorescence polarization of DPH, as well as (Na+ + K+)ATPase activity, did not change significantly during the whole treatment. However, the extra addition of ethanol (0.175-0.700 M) in vitro to the membranes of rats, having received ethanol over a period of at least 2 weeks, fluidized less and inhibited the (Na+ + K+)ATPase activity less than in starch-fed controls. The time-course for the appearance of this membrane hyposensitivity was found to be the same as the time course for the development of functional tolerance to ethanol. The correlation between the degree of functional tolerance and the (Na+ + K+)ATPase sensitivity to ethanol appeared very significant, highlighting the sensitivity of membrane-bound enzymes to detecting adaptive changes in complex biological membranes tolerance.

Brain membrane disordering by administration of a single ethanol dose.

There is a bulk of evidence that ethanol exerts an important direct effect on biological membranes, especially in the central nervous system, during chronic administration. Whether membranes are affected after an acute and subacute ethanol administration remains to be demonstrated. Crude synaptic membrane fluidity (checked by fluorescence polarization) together with (Na+ +K+)ATPase activity were therefore examined 18 hours after a single oral ethanol administration (5 g/kg bwt.) to naive rats or to rats previously intubated with ethanol repeatedly during 4 days (increasing the daily dose from 7 to 10 g/kg). The sensitivity of both parameters to different concentrations of ethanol added in vitro (0.175 M-1.400 M) was also determined. Although no changes in the basal intrinsic fluidity were found, (Na+ +K+)ATPase activity increased slightly after administration of ethanol to naive as well as to short-term ethanol intoxicated rats. The fluidizing as well as the ATPase inhibiting effects following the addition of ethanol in vitro were markedly increased 18 hours after ethanol administration to naive rats. Such an hypersensitization seems not to be related to an unspecific stress or to changes in body temperature and was no longer apparent in short-term ethanol intoxicated rats. Disappearance of the acute ethanol induced hypersensitization with further ethanol administration may represent the first stage of tolerance acquisition.

Brain membrane disordering related to acute ethanol administration in naive and short-term ethanol-intoxicated rats.

Crude synaptic membrane fluidity (checked by fluorescence polarization) together with (Na+ + K+) ATPase activity were examined 18 hours after a single oral ethanol administration (5 g/kg bwt.) to naive rats and to rats previously intubated with ethanol repeatedly during 4 days. The sensibility of both parameters to different concentrations of ethanol added in vitro (0.175 M-1.400 M) was also determined. Although no changes in the basal intrinsic fluidity were found, (Na+ + K+)ATPase activity increased slightly in both conditions. The fluidizing as well as the ATPase inhibiting effects following the addition of ethanol in vitro were markedly increased 18 hours after ethanol administration to naive rats. This hypersensitization was no longer apparent in rats pretreated with ethanol during 4 days. The acute ethanol-induced hypersensitization found in naive rats appears not to be related to an unspecific stress or to changes in body temperature. The disappearance of this hypersensitization in short-term alcohol-intoxicated animals may represent the first stage of tolerance acquisition.