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

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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.

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Fig. 1

(From Krikun et al. 1994)

Fig. 2

(Modified from Wu et al. 2011)

Fig. 3

(From Rand et al. 1998)

Fig. 4

Drawing modified from original published in Taatjes et al. (2013)

Fig. 5

(From Rand et al. 2003)

Fig. 6

(From Rand 2010)

Fig. 7

(From Rand et al. 2008)

Fig. 8

(From Rand et al. 2010b)

Fig. 9

Images originally published in Taatjes et al. (2014)

Fig. 10

[Images originally published in Taatjes et al. (2014)]

Fig. 11

Figure modified from original version published in Taatjes et al. (2017)

Fig. 12

Figure modified from original version published in Taatjes et al. (2017)

Fig. 13

(From Rand et al. 2017)

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Acknowledgements

First, we express our gratitude to Dr. Edwin (“Ted”) Bovill who brought the authors together to initiate a long-standing and enriching research collaboration. We thank Nicole Bouffard, Anthony Quinn, and Michele von Turkovich for excellent technical assistance for the microscopic imaging portions of this manuscript, Dr. Xiao Xian Wu for her key roles in advancing this project, and Mr. Laurence A. Guerino for his office support in the preparation of this manuscript. The projects described were supported by Award number S10RR025498 from the National Center for Research Resources (DJT) for the purchase of the atomic force microscope.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

    Jacob H. Rand

  2. Department of Pathology and Laboratory Medicine, and Microscopy Imaging Center, Larner College of Medicine, University of Vermont, 89 Beaumont Avenue, Burlington, VT, 05405, USA

    Douglas J. Taatjes

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  1. Jacob H. Rand
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Correspondence to Douglas J. Taatjes.

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Rand, J.H., Taatjes, D.J. Reimagining the antiphospholipid syndrome, an enigmatic thrombophilic disorder, through the looking glass of microscopic imaging. Histochem Cell Biol 150, 529–543 (2018). https://doi.org/10.1007/s00418-018-1709-2

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