Understanding AL amyloidosis with a little help from in vivo models.

Monoclonal immunoglobulin (Ig) light chain amyloidosis (AL) is a rare but severe disease that may occur when a B or plasma cell clone secretes an excess of free Ig light chains (LCs). Some of these LCs tend to aggregate into organized fibrils with a ß-sheet structure, the so-called amyloid fibrils, and deposit into the extracellular compartment of organs, such as the heart or kidneys, causing their dysfunction. Recent findings have confirmed that the core of the amyloid fibrils is constituted by the variable (V) domain of the LCs, but the mechanisms underlying the unfolding and aggregation of this fragment and its deposition are still unclear. Moreover, in addition to the mechanical constraints exerted by the massive accumulation of amyloid fibrils in organs, the direct toxicity of these variable domain LCs, full-length light chains, or primary amyloid precursors (oligomers) seems to play a role in the pathogenesis of the disease. Many in vitro studies have focused on these topics, but the variability of this disease, in which each LC presents unique properties, and the extent and complexity of affected organs make its study in vivo very difficult. Accordingly, several groups have focused on the development of animal models for years, with some encouraging but mostly disappointing results. In this review, we discuss the experimental models that have been used to better understand the unknowns of this pathology with an emphasis on in vivo approaches. We also focus on why reliable AL amyloidosis animal models remain so difficult to obtain and what this tells us about the pathophysiology of the disease.

A simple new screening tool for diagnosing imported schistosomiasis.

Objectives: We sought to test the sensitivity and feasibility of a Schistosoma infection screening process consisting of a scored patient consultation questionnaire and a serological diagnostic test. Study design: Prospective cross-sectional study. Methods: We collected from Schistosoma-exposed individuals a 14-point check list of clinical and laboratory data related to Schistosoma infection, alongside a serological test to detect Schistosoma spp infection. A check list score was created and compared with the risk of infection and clinical recovery through an agreement analysis. Results: Two-hundred and fifty individuals were enrolled, of whom 220 (88%) were male and 30 (12%) female. The median age was 39 (range 18-78). One hundred-fifty (60%, 95% CI 54.9%-65.1%) had a check-list score ≥2. Serology test results were positive for 142 (56.8%, 95% CI 51.6%-62%). Chronic complications compatible with long-term Schistosoma infection were detected in 29 out of these 142 (20.4%, 95% CI 13.8%-27%).,. The median score value was 3, the area under the receiver operating characteristic (ROC) curve against serology results was 0.85 and the estimated intercept check-list questionnaire score value was 1.72 (95%, CI: 1.3-2.2). Participants with a positive serological test had a substantially higher check-list score (Cohen's kappa coefficient: 0.62, 95% CI: 0.54-0.70). Ninety four percent patients empirically treated showed a subsequent improvement in clinical and laboratory parameters. Conclusions: A two-component process consisting of a scored patient consultation questionnaire followed by serological assay can be a suitable strategy for screening populations at high risk of schistosomiasis infection.