Assessment of splenic function

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell–Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, 99mTc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field