Acquired factor V inhibitor in a context of sepsis and disseminated intravascular coagulation

International audienc

Use of Sysmex XE-2100 and XE-5000 hematology analyzers for the diagnosis of malaria in a nonendemic country (France).

INTRODUCTION: Most studies dealing with automated hematology analyzers (HAs) and malaria diagnosis are conducted in endemic countries. METHODS: We retrospectively studied cell blood counts (CBCs) performed with Sysmex XE-2100 and XE-5000 HAs in our center (Angers, France) regarding 67 patients returning from endemic areas and infected with various Plasmodium species. RESULTS: In 83% of infected samples with Plasmodium vivax (Pv), ovale (Po), or malariae (Pm), extra clouds of dots were present in neutrophil and/or eosinophil area(s) on routine differential (DIFF) scattergrams. In contrast, samples infected with Plasmodium falciparum (Pf) failed to show such DIFF scattergrams, or any other suggesting malaria infection (0/ 49 pts). Abnormal areas from DIFF scattergrams were related to the presence of mature schizonts and gametocytes, undestroyed by lysis agent, the latter not observed in Pf-infected patients from our series. The internal parameter WBC[DIFF] - WBC[BASO] raised in parallel to parasitemia in Pv, Po, and Pm samples but could not be used as a surrogate for parasitemia. In Pf infection, reticulocyte/ immature reticulocyte fraction (IRF) ratio showed a significant correlation with parasitemia (P < 0.05). A diagnostic model developed for Pf in endemic countries showed sensitivity of 77%. CONCLUSION: Using SYSMEX analyzers, Pv, Po, and Pm infections are easy to ascertain as DIFF scattergrams are almost specific (specificity = 99.9%). Pf infection diagnosis by CBC may be a more promising tool

Double reactivity against actin and alpha-actinin defines a severe form of autoimmune hepatitis type 1

Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH-1). Recently, the binding domain of alpha-actinin on actin was shown to be a predominant epitope. To test this reactivity, an anti-alpha-actinin enzyme-linked immunosorbent assay was developed, and positivity confirmed by Western blot. Anti-alpha-actinin antibody was found in 21/50 (42%) of AIH-1 patients, compared with 52/401 (12.9%) of liver disease control patients, and with 6/200 (6%) of blood donors. Anti-filamentous and anti-alpha-actinin activities were found specifically together in 66% of anti-filamentous-positive AIH-1 patients. This combination of specificities reflected clinical and histological disease activity, short duration and absence of treatment. Finally, using an actin-alpha-actinin complex assay, the binding of anti-filamentous actin to alpha-actinin-binding domain on actin was demonstrated, as well as that of anti-alpha-actinin on the actin-binding domain of alpha-actinin. Thus, the frequent combination of anti-filamentous and anti-alpha-actinin antibodies seems to be the hallmark of activity in AIH-1

Glomerular antibodies in lupus nephritis.

International audienceLupus nephritis (LN) remains the most common severe manifestation of systemic lupus erythematosus (SLE) characterized by the presence of autoantibodies (Abs) that are believed to play a central role in the pathogenesis of LN. Among more than 100 Abs reported in SLE, only a few display a direct glomerular binding capacity. Such antiglomerular Abs are detected at the onset of the disease before antinuclear Abs detection and proteinuria, this detection is associated with the related autoantigen overexpression. Antiglomerular Abs are able to interfere with cell metabolism, to penetrate living cells, and to induce glomerular cell proliferation. In addition, antiglomerular Abs could be nephritogenic causing proteinuria, particularly when they cross-react with anti-dsDNA Abs. Antiglomerular Abs encompass anti-α-actinin, anti-laminin-1, antifibronectin, antimyosin, and anticollagen Abs. The pathogenic activity of anti-α-actinin Abs has been demonstrated in non-autoimmune mice after immunization with α-actinin, but not with dsDNA, leading to a SLE-like disease with proteinuria and glomerular immune complex deposition. Similarly, extracorporeal immunoabsorption to remove anti-laminin-1 Abs reduces kidney-Abs deposition and proteinuria in mice and humans proving their pathogenic effect. Altogether this suggests that antiglomerular Abs participate, at least at the beginning, in the glomerular immune complex deposition and in the kidney damage