Effect of mirasol pathogen reduction technology system on immunomodulatory molecules of apheresis platelets.

Pathogen inactivation for platelets by riboflavin system (MIRASOL) efficiently reduces transfusion related pathogen transmission. However little is known about its impact on platelets' immunomodulatory biochemical profile. We aimed was to assess the effects of MIRASOL treatment on platelet quality parameters and immunomodulatory molecules CD62P, RANTES, and CD40L in Single Donor Platelets (SDPs) resuspended in plasma (SDP-P) or T-PAS and additive solution (SDP-A). Twenty nine SDPs (15 SDP-P and 14 SDP-A) were included in the study. Samples were collected before, after MIRASOL treatment and just before transfusion. P-selectin (CD62P), RANTES, and CD40L were tested by ELISA. Platelet products quality assays were also performed. Platelet count/unit decreased after Mirasol treatment by 13 %. The pH of all units decreased over the 5-day storage period but remained above expected limits and the swirling test was positive throughout storage. P-selectin levels were not different between the three different time points in both SDPs-P and SDPs-A while RANTES levels were found to differ statistically significantly at the three different time points in all units and in the SPD-A subgroup. CD40L levels in all SDP products increased slightly during storage but this was not statistically significant. CD62P, RANTES, and CD40L in all time points were elevated in SDPs-A compared to SDPs-P but not at a statistically significant level. In conclusion MIRASOL treatment apart from RANTES increase does not seem to substantially affect platelets associated other cytokines and immunomodulatory molecules namely P-selectin and sCD40L which are implicated in immune transfusion reactions.

Effect of angiotensin converting enzyme gene I/D polymorphism and its expression on clinical outcome in acute respiratory distress syndrome.

BACKGROUND: The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. Our aim was to assess simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of patients with ARDS. METHODS: Sixty-nine mechanically ventilated patients with ALI/ARDS were recruited. ACE activity levels both in serum and BALF were assessed by chemical methods. Patients were genotyped for ACE I/D polymorphisms. Time-to-event analysis evaluated the variables associated with the 28-day and 90-day mortality. Finally, we performed a meta-analysis of studies examining the association between ACE I/D polymorphisms and mortality of ALI/ARDS patients. RESULTS: In the multivariable model, age, lung compliance, serum lactate and serum ACE levels were significantly associated with both 28- and 90-day mortality. No significant correlation was found between serum and BALF ACE levels (Spearman's rho=0.054; P=0.66). Serum ACE concentrations were significantly higher (P=0.046) in patients with D/D genotype versus the two other groups combined (I/D and I/I genotypes). The meta-analysis of 6 studies (including ours) provided evidence that D allele is significantly associated with increased mortality in ALI/ARDS patients, yielding a per-allele odds ratio of 1.76 (95% CI: 1.19, 2.59). CONCLUSION: Serum ACE levels appear to be affected by the I/D polymorphism and are correlated with prognosis in patients with ALI/ARDS indicating that further investigation of the clinical significance of the ACE in ARDS might be of value.

Comparison of evidence of treatment effects in randomized and nonrandomized studies.

CONTEXT: There is substantial debate about whether the results of nonrandomized studies are consistent with the results of randomized controlled trials on the same topic. OBJECTIVES: To compare results of randomized and nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between randomized and nonrandomized studies. DATA SOURCES: MEDLINE (1966-March 2000), the Cochrane Library (Issue 3, 2000), and major journals were searched. STUDY SELECTION: Forty-five diverse topics were identified for which both randomized trials (n = 240) and nonrandomized studies (n = 168) had been performed and had been considered in meta-analyses of binary outcomes. DATA EXTRACTION: Data on events per patient in each study arm and design and characteristics of each study considered in each meta-analysis were extracted and synthesized separately for randomized and nonrandomized studies. DATA SYNTHESIS: Very good correlation was observed between the summary odds ratios of randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; P =.009). Between-study heterogeneity was frequent among randomized trials alone (23%) and very frequent among nonrandomized studies alone (41%). The summary results of the 2 types of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance were less common when only prospective studies were considered (8%). Occasional differences in sample size and timing of publication were also noted between discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%), the odds ratio varied at least 2-fold between nonrandomized studies and randomized trials. CONCLUSIONS: Despite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.

Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin.

OBJECTIVE: To study the prevalence of different causes of anaemia in patients with systemic lupus erythematosus (SLE) and their associations with immunological and clinical parameters and to evaluate the contribution of erythropoietin (Epo) and anti-erythropoietin (anti-Epo) autoantibodies to the development of SLE anaemia. METHODS: 132 SLE patients with anaemia (defined as haemoglobin of 12 g/dl or less for women and 13.5 g/dl or less for men) from among a total of 345 consecutive SLE patients were prospectively enrolled into the study. Standard haematological and immunological tests were performed and serum Epo and anti-Epo antibodies were assayed. RESULTS: The identified causes were anaemia of chronic disease (ACD) n=49 (37.1%), iron deficiency anaemia (IDA) n = 47 (35.6%), autoimmune haemolytic anaemia (AHA) n = 19 (14.4%) and other causes n = 17 (12.9%). There was significant heterogeneity in the severity of anaemia between the four groups (p<0.01) with AHA cases being on average more severe. The proportion of patients with anticardiolipin antibodies, low complement levels and anti-dsDNA differed significantly among the four groups; these markers were particularly common in patients with AHA, and uncommon in patients with IDA. Twenty one of 100 tested patients had anti-Epo antibodies. Such antibodies were seen practically only in patients with ACD (odds ratio 3.1, p = 0.041) and in patients with high lupus activity (ECLAM) scores (odds ratio 1.27 per point, p = 0.055). Epo response was inadequate in 42.4% and 41.2% of patients with ACD and AHA, respectively. CONCLUSIONS: Anaemia in SLE usually takes the form of ACD and IDA, however autoimmune haemolysis is not uncommon. SLE patients with different causes of anaemia differ in regard to several immunological parameters. Epo response is blunted in anaemic SLE patients, particularly those with ACD and AHA.

Autoimmune hemolytic anemia in patients with systemic lupus erythematosus.

PURPOSE: We sought to evaluate the clinical and serologic associations with, and outcomes of, autoimmune hemolytic anemia, as compared with other types of anemia, in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: We studied 41 consecutive patients with SLE with clinically manifest autoimmune hemolytic anemia, including 27 (66%) in whom hemolysis was the initial disease manifestation. We matched each patient for age and disease duration with a patient with SLE with anemia resulting from a different cause. RESULTS: The 41 patients had a total of 50 episodes of autoimmune hemolytic anemia. The recurrence rate was 4 per 100 person-years. Cases and controls had similar mean (+/- SD) lupus activity indexes (2.1 +/- 1.5 vs 2.4 +/- 1.3, P = 0.5). Patients with autoimmune hemolytic anemia at any time could be distinguished from patients with other causes of anemia, because they were more likely to have elevated titers of IgG anticardiolipin antibodies [odds ratio (OR) = 5.8; 95% confidence interval (CI), 1.4 to 24] and thrombosis (OR = 4.6; 95% CI, 1.0 to 21). Autoimmune hemolytic anemia at the onset of SLE was independently associated with renal involvement (OR = 5.4; 95% CI, 1.0 to 28), thrombocytopenia (OR = 7.3; 95% CI, 1.1 to 48), and possibly thrombotic episodes during follow-up (OR = 11; 95% CI, 0.8 to 160) when compared with controls with other types of anemia at the onset of SLE. CONCLUSIONS: Autoimmune hemolytic anemia usually occurs at the onset of SLE, and its recurrence rate is low among treated patients. The association with IgG anticardiolipin antibodies and thrombosis suggests that the occurrence of autoimmune hemolytic anemia may define a subgroup of patients with SLE who have characteristic serologic and clinical manifestations.

Circulating autoantibodies to erythropoietin are associated with human immunodeficiency virus type 1-related anemia.

In a cohort of 204 unselected consecutive human immunodeficiency virus type 1 (HIV-1)-infected patients, the association of circulating autoantibodies to endogenous erythropoietin (EPO) with HIV-1-related anemia was studied. Circulating autoantibodies to EPO were present in 48 (23.5%) of the 204 patients studied. Circulating autoantibodies were an independent predictor of anemia (odds ratio [OR]=5.0; 95% confidence interval [CI], 2.5-9.9), as strong as other known causes of anemia. The association of anti-EPO antibodies with anemia became stronger when the analysis was limited to the group of patients without any medical condition causing anemia (OR=10.4; 95% CI, 3.2-33.9). Moreover, the effect on hemoglobin levels remained significant even after adjusting for other anemia parameters. Anti-EPO autoantibodies were associated with higher EPO levels (r=.25, P=.012) and with a more prominent EPO response to anemia. Our findings suggest that autoimmunity, among other factors, may contribute to the pathogenesis of HIV-1-related anemia.

Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: correlation with anemia.

OBJECTIVE: To investigate the existence of circulating autoantibodies to erythropoietin (EPO) in sera from patients with systemic lupus erythematosus (SLE), and to correlate their presence with anemia and clinical activity. METHODS: Ninety-two consecutive patients with SLE, 80 patients with rheumatoid arthritis, and 42 normal individuals were studied. The patients with SLE were categorized into 3 groups according to hemoglobin (Hgb) level: group A (45 patients with Hgb > 12 gm/dl), group B (26 patients with Hgb 10.1-12 gm/dl), and group C (21 patients with Hgb < or = 10 gm/dl). In all patients with SLE, the disease activity was evaluated using the European Consensus Lupus Activity Measurement scale. Antibodies to EPO were detected using an enzyme-linked immunosorbent assay and purified recombinant human EPO as antigen. The specificity of the method was evaluated with homologous and cross-reactive inhibition assays. RESULTS: Antibodies to EPO were found in 15.2% of the SLE patient sera. The distribution of these antibodies among the 3 groups of SLE patients was as follows: 8.8% (4 of 45) from group A, 15.4% (4 of 26) from group B, and 28.6% (6 of 21) from group C. The prevalence of antibodies to EPO in patients with severe anemia (group C) was statistically significantly higher compared with patients without anemia (chi(2) = 4.31, P < 0.05). Patients with antibodies to EPO had higher disease activity scores (P < 0.005) and lower levels of the C4 component of complement (P < 0.05) compared with patients without antibodies to EPO. CONCLUSION: In this study, the presence of antibodies to EPO in the sera of SLE patients is demonstrated for the first time. The presence of these antibodies is associated with severe anemia and active disease.