Reimagining the antiphospholipid syndrome, an enigmatic thrombophilic disorder, through the looking glass of microscopic imaging

Abstract

The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder that was described as a diagnostic entity over 30 years ago. And yet the pathogenic mechanisms that are responsible for its clinical manifestations remain to be definitively established. The syndrome is defined by (1) the concurrence of vascular thrombosis and/or pregnancy complications together with (2) positivity for immunoassays and coagulation tests that were derived from clinical observations of two anomalous laboratory test results-specifically, false positivity for syphilis infection in uninfected individuals and the finding of inhibitors of blood coagulation in patients who lacked any bleeding tendencies. Over the years, these were standardized into immunoassays and coagulation assays for APS. Here, we describe how prior knowledge of the immunologic and coagulation aspects of the disorder led to research involving a range of imaging modalities including light microscopy, immunohistochemistry, confocal scanning laser microscopy, transmission and scanning electron microscopy, and atomic force microscopy. In turn, the results from those studies led to a "reimagining" of APS that has advanced the understanding of pathogenic mechanisms of the disorder and has led to the development of novel mechanistically based diagnostics along with potential new treatment approaches that target disease mechanisms.

In focus in HCB

“…Two reviews focus on aspects of peroxisomes, from their biological functions and their role in various disease processes (Islinger et al 2018), to how cells maintain peroxisome homeostasis via selective autophagy, and the physiological consequences of misregulation of this process (Eberhart and Kovacs 2018); Mattes and Scholpp (2018) describe the function of the signaling protrusions termed cytonemes and tunneling nanotubes in cell-cell communication; Saraste and Marie (2018) provide an update on aspects of the autonomous cellular intermediate compartment; Groeneweg and colleagues (2018) present a timely review on aspects of gephyrin regulation of synapses; Rand and Taatjes (2018) review the use of various microscopy-based imaging techniques to investigate the antiphospholipid syndrome, a human thrombotic disorder; and the last two reviews cover instrument/technique applications for cell biology: Pirozzi and colleagues (2018) describe "ColorEM", analytical nanoscale techniques encompassing energy-dispersive X-ray analysis, electron energy loss spectroscopy, and cathodoluminescence combined with electron microsocopy for investigating elements and molecules from the tissue to the cellular to the organelle level (see cover image); and Segura-Valdez and colleagues (2018) describe the use of atomic force microscopy for the imaging of internal cellular structures.…”