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Abstract: Red blood cell allo-immunization is the immune response of an individual to foreign red blood cell antigens not present on the surface of their own cells. The aim of that paper is to clarify the different factors influencing the antibody response against red blood cell antigens. [Copyright &y& Elsevier]

Abstract: A rare blood group is usually defined as the absence of a high prevalence antigen or the absence of several antigens within a single blood group system, if its prevalence in France is 4/1000 or less in the general population. An individual with a rare blood phenotype can develop a naturally-occurring or immune antibody corresponding to his rare specificity. In case an extremely low stock of compatible blood is available at the national level, a so-called “transfusion deadlock” is described. Most of the individuals with a rare blood group are coincidently identified when a routine pretransfusion testing or pregnancy follow-up is performed, if the antibody(ies) corresponding to the rare specificity is(are) present. Other individuals are discovered following a systematic red cell typing, or family investigations in siblings. One hundred and twenty-one rare blood specificities and 42 rare blood genotypes are currently defined at the French National Reference Laboratory for Blood Groups (CNRGS–Paris). The French national registry of individuals with a rare blood phenotype/genotype includes about 9600 people, who are urged to regularly donate blood for the National Rare Blood Bank. This bank, based on a homologous blood transfusion program, is in charge of the long-term storage of rare frozen blood units, that can only be delivered after receiving authorization from the CNRGS. The global and individual care management of the individuals with a rare blood group, concerning potentially several hundred thousand people in France, requires a close cooperation between all the protagonists within the transfusion chain. [Copyright &y& Elsevier]

Mixed cryoglobulinaemia is associated strikingly with HCV infection. The aim of this study was to assess whether the adherence to proper methods of collecting samples for cryoglobulin detection was critical or not on virological parameters in hepatitis C virus (HCV) patients. We studied 56 consecutive patients. Blood samples were collected using a conventional method and a blood collection method at 37°C adapted to cryoglobulin detection. HCV core antigen and HCV RNA were measured in sera and cryoglobulins issued from both blood collection methods. In cryoglobulin-positive patients, serum concentrations of HCV core antigen, but not that of HCV RNA, were significantly higher when a conventional method was used, compared to a blood collection method at 37°C ( P = 0·001). In the cryoprecipitates, concentration of HCV core antigen was optimum when the blood collection method at 37°C, rather than the conventional method, was applied for cryoglobulin detection ( P < 10−4). The recovery of HCV core antigen in the cryoprecipitate was improved when cryoglobulins were isolated using the blood collection method at 37°C rather than the conventional method ( P < 0·001). HCV parameter measurements and cryoglobulin study should not be performed on the same serum samples due to the potential impact of blood collection methods on results. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate performance of the clinical laboratories for the detection of antinuclear antibodies (ANA) by using indirect immunofluorescence method (IIF), in France. A national external quality assessment (EQA) on ANA detection was organized by the French health products safety agency once a year since 1998. Between 606 to 687 laboratories together with six university reference laboratories experienced in performing tests in autoimmunity participated in the six-year consecutive survey. Each laboratory had to answer to methodological procedures and give coded responses. Variability in IIF methodological procedure was observed. Use of inappropriate microscope magnifications for reading slides or nonconventional cutoff dilution of serum were pointed out to concerned laboratories. Concerning ANA measurement, the rate of good responses ranged from 92.7% to 99.5% of the laboratories when the samples contained ANA. A wide dispersion of ANA titers obtained on a same sample was repeatly observed every year. Misinterpretation of particular fluorescence pattern was noticed. On ANA negative sample, the rate of good responses was 94.3%. In conclusion, ANA detection in routine practice is far from being standardized. However, EQA may have an impact on ANA detection performance when it is conducted on several consecutive year surveys, by providing advice for participating laboratories to limit inter laboratory variations related to methodological procedures. [ABSTRACT FROM AUTHOR]

The pathogenic mechanisms that lead to chronic hepatitis C are unknown. As hepatitis C virus (HCV) has been shown to induce T cell response, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver of patients with chronic hepatitis C in relation to viraemia or HCV genotypes. The immunophenotypes of liver-derived lymphocytes were analysed in 26 patients by flow cytometry and immunohistochemistry. Viraemia was quantified by branched DNA assay. Using this assay, HCV RNA was not detectable in six patients. HCV RNA was detected in 20 patients, and titres ranged from 8 to 137 × 106 Eq/ml. Genotyping was performed using a line probe assay. Type 1a, 1b, 2a, 3a and 4a were found to infect 2, 10, 2, 7 and 3 patients, respectively. The CD4+/CD8+ ratio of liver-derived lymphocytes was significantly higher (P < 0.01) in patients with detectable viraemia than in patients without detectable viraemia. In contrast, neither the percentage of γ/δ T lymphocytes nor that of CD2+CD57+ cells was different in the groups. When comparing the CD4+/CD8+ ratio, the percentage of γ/δ T lymphocytes or CD2+CD57+ cells according to genotype, the differences were not significant. These results suggest that the CD4+/CD8+ ratio of liver-derived lymphocytes is related to viraemia but not to HCV genotypes in patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

T lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver-derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388 pg/mI at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication, CD4+/CD8+ ratios of liver-derived lymphocytes were significantly higher (P < 0.05) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the γ/δ receptor and that of CD2+/CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication, CD4+/CD8+ ratios of liver-derived lymphocytes correlated with serum HBV DNA levels (P < 0.001). No relationship between CD4+/CD8+ ratio of liver-derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B. the CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytoxic T cell activity in patients with HBV-related chronic hepatitis. [ABSTRACT FROM AUTHOR]

Polyclonal B cell activity in systemic lupus erythematosus (SLE)may be under T cell control. The use of nitrocellulose irnmunoblots for the analysis of recognition by peripheral blood lymphocytes of nucleoplasmic proteins in SLE patients led to the characterization of significant proliferative responses to 68K (UI RNP): SS-B: B-B' and D (Sm) antigen in 15 of 20 patients. Variations of proliferative response were parallel to disease activity over a follow-up period of &ges; 6 months. conferring some prognostic value to the assay of lymphocyte response to nucleoplasmic antigens. The pattern of reactivity differs from the corresponding serum antibody profile, and purified T cell suspensions ( >95% pure) were shown to proliferate in response to soluble nucleoplasmic antigens, indicating that T and B cell repertoires against nucleoplasmic proteins may differ. This suggests that activated helper T cells contribute to the fine modulation of B cell reactivity to subcellular particles to determine the particular antibody profile of the patients. [ABSTRACT FROM AUTHOR]

Dear Editor, Chronic spontaneous urticaria (CSU) is an inflammatory disease characterized by spontaneous weals or angio-oedema for more than 6 weeks. International guidelines from the EAACI/GA SP 2 sp LEN/EDF/UNEV were published in 2018,1 but practice remains heterogeneous, especially for CSU refractory to H SB 1 sb antihistamines and regarding states' official drug approval and reimbursement policies. 3 (iii) The working group does not recommend the adjunction of H SB 2 sb antihistamines or montelukast to H SB 1 sb antihistamines in CSU, owing to the lack of demonstrated efficacy. [Extracted from the article]

The article presents questions and answers related to red blood cells for patients who are negative for a high-frequency antigen including the definition of a rare donor, problems encountered in finding compatible red blood cells (RBC) for patients, and whether countries have a national panel of rare donors and/or a national bank of frozen (RBC) units from such donors.

Current models used to predict response to peginterferon plus ribavirin treatment, based on viral decline during the first 12 weeks of therapy, have focused on creating an early stopping rule to avoid unnecessary prolongation of therapy. We developed a multivariate model that predicted sustained virological response and nonresponse at baseline and during the first 12 weeks of therapy using collected data from 186 unselected patients with chronic hepatitis C treated with peginterferon plus ribavirin. This model employed ordinal regression with similarity least squares technology to assign the probability of a given outcome. Model variables include sex, age, prior treatment status, genotype, baseline serum alanine aminotransferase levels, histologic necroinflammation and fibrosis scores and serum hepatitis C virus RNA concentration at baseline and weeks, 4, 8, and 12. A multivariate model demonstrated high performance values at all time points. At baseline, the model demonstrated a negative predictive value (NPV) and a positive predictive value (PPV) of 91% and 95%, respectively. At week 4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89% specificity and 93% accuracy. At week 4, the model was equally efficient for naïve or previously treated patients. Internal validation demonstrated 90% PPV, 94% NPV, 95% sensitivity, 88% specificity and 92% accuracy. A week 4 stopping rule for patients with chronic hepatitis C treated with peginterferon with ribavirin might be proposed by using the model developed in our study. [ABSTRACT FROM AUTHOR]

Background: Isolated sinusoidal dilatation is an uncommon hepatic lesion and the cause is largely unknown. Objective: To investigate whether prothrombotic disorders or perisinusoidal cell changes could be involved in pure idiopathic hepatic sinusoidal dilatation (HSD). Methods: Evaluation for associated conditions, prothrombotic disorders, and studies of hepatic perisinusoidal cell activation in consecutive patients, seen between 1993 and 2002, with isolated sinusoidal dilatation unrelated to outflow block, sinusoidal infiltration, or hepatic granulomas. Results:Among 11 patients, associated conditions were prothrombotic disorders (n = 5) and oral contraceptive use (n = 3). Prothrombotic disorders were polycythemia vera (n = 1) and anticardiolipin antibodies combined with lupus anticoagulant (n = 4). No genetic thrombophilia factor was found. Of four patients with lupus anticoagulant, three had antinuclear factors and high serum levels of anticardiolipin antibodies at repeated testing. There was no evidence of intrahepatic or extrahepatic thrombosis in any of the patients. Sinusoidal dilatation was marked in six of 11 patients (54%), including two patients with antiphospholipid antibodies. Activated perisinusoidal cells were only found around markedly dilated sinusoids. Conclusion: Idiopathic pure HSD is frequently associated with the immunological features of the antiphospholipid syndrome. Therefore, finding pure HSD in a liver biopsy specimen should prompt the search for antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]

Aim: To evaluate 5-year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow-up. Methods: In a non-concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow-up. Results: The 5-year survival rates were 43% in the 122 patients and 66%, 50% and 25% in Child–Pugh class A, B and C patients, respectively. In multivariate analysis, age (P = 0.01), Child–Pugh score (P = 0.0001), gastrointestinal bleeding (P = 0.01), presence of HBs Ag and/or anti-HCV (P = 0.03), smoking (P = 0.01), absence of histologically proven alcoholic hepatitis (P = 0.05) and persistent alcohol intake (P = 0.002) were associated with significantly increased risk ratios of death. Conclusions: In hospitalised patients with excessive alcohol intake and cirrhosis: (1) age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are independent poor prognostic markers, (2) smoking may contribute to the aggravation of cirrhosis, and (3) alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favourable prognostic significance. [ABSTRACT FROM AUTHOR]

Abstract: Background: The use of blood group genotyping for the prediction of antigen expression has been discussed in clinical transfusion settings, but much less for reagent red blood cells selection. In France, the Centre National de Référence pour les Groupes Sanguins (CNRGS) produces a reference panel of reagent red blood cells, mainly used for red cell antibody identification. The use of high-throughput DNA analysis has never been applied to blood donors whose red blood cells are used as reagents. The aim of this study was to compare the serological phenotype and that predicted from DNA analysis in such donors, and to determine the benefit of DNA analysis in reagent red blood cells selection strategy. Study design and method: Red blood cells of 346 blood donors were typed with two different reagents for each antigen. The genotyping was performed by using HEA v1.2 BeadChips, BioArray Solutions, Immucor. The comparison between the serologically determined phenotype and that predicted from DNA analysis held on 8876 paired results obtained from 10 blood group systems and 25 antigens. Results: A 99.95% concordance was observed. Four cases of discrepancy for RH, KEL, LU and DO blood group systems were analyzed. Genotyping precisions were of special interest for the Duffy blood group system. Conclusion: Systematic DNA analysis brings important information on reagent red blood cells selection. It can be used at a routine level. Especially, the notion of “antigen of double dose” which is specified in several countries by government bodies should evolve regarding data obtained from DNA analysis. This should improve the quality of reagent red blood cells as first step for antibody identification. [ABSTRACT FROM AUTHOR]