In Memoriam

Silvia Pierangeli was one of the most respected, prolific and well-liked investigators in the field of antiphospholipid antibody (aPL)/antiphospholipid syndrome (APS) research. In the course of a 25-year academic career, she combined passion for her work, talent, prodigious energy, an ability to pursue several tasks at once, a winning personality, an abiding spirit of generosity, and a strong association with colleagues across the globe. Born in Buenos Aires, Argentina, to Dr. Hector and Mrs. Suzanna Pierangeli, who were themselves of scientific background and owned and operated a diagnostic laboratory in Buenos Aires, Silvia was educated at Buenos Aires National University where she received a PhD degree in Biochemistry. After working in her parents’ laboratory for a few years, she went on to start one of her own. In 1986, she was awarded a Fulbright Scholarship and moved from Argentina with her husband and two young children to the University of Louisville in Louisville, Kentucky, where she received her second PhD degree in Microbiology and Immunology. Dr. Pierangeli joinedme (E.N.H.) as a postdoctoral fellow in 1987 to start what we named the Antiphospholipid Standardization Laboratory. As that name suggests, our major interest at the time was in popularizing and advocating a standard method for performance of the anticardiolipin antibody (aCL) test and investigation of the specificity of aCL antibodies and the lupus anticoagulant, with particular interest in the differential specificity of aCL antibodies produced in APS versus infectious diseases. By the mid-1990s, interest expanded to the mouse model of thrombosis and exploration of the pathogenesis of aPLs in APS using this in vivo model. By the first decade of the 21st century, Dr. Pierangeli’s interests grew exponentially in using in vivo and in vitro strategies to probe cellular and intracellular effects of aPL as well as studies of biological agents that might ameliorate the clinical complications of APS. Her contributions fall into four major categories (1) standardization of aCL and anti-β2-glycoprotein I (anti-β2GPI) tests; (2) usingmouse models of thrombosis and fetal loss to study the pathogenic effects of aPLs and mechanisms by which these antibodies might be induced; (3) investigation of agents that ameliorate the effects of these antibodies so offering possible treatment options; and (4) development of a unique assay that distinguishes aPL in APS versus those produced in other disorders. Dr. Pierangeli’s work on standardization of the aCL and more recently, the anti-β2GPI test extended over 25 years. Recognizing the significant variability in performance of the tests and test results, she embarked on a tireless effort to promote standard test performance through multiple publications, workshops, membership in International Committees interested in standardization efforts, and making herself available to provide advice to countless laboratories and groups worldwide. Her efforts culminated in the assembly of experts 2 years ago to reach consensus on performance of the aCL and anti-β2GPI assays, whichwas published recently.1 In addition, she was made chairman of the Clinical and Laboratory Standards Institute (CLSI) Document Development Committee on Antiphospholipid Antibodies, which is engaged in formalizing standard methods for the aCL and anti-β2GPI enzyme-linked immunosorbent assays (ELISA). Focusing on the anti-β2GPI test, Dr. Pierangeli assembled another group of experts to prepare reference calibrators for the assay (using an approach similar to that used in 1986 to prepare aCL calibrators) and to develop units ofmeasurement for levels of anti-β2GPI antibodies, which are expected to be adopted universally. Of special note for this journal were several contributions in specially aPL/APS themed issues in both 2012 and 2008.2–6 Dr. Pierangeli’s second area of work involved mouse models of thrombosis and fetal loss. The model entails the use of anesthetized mice whose femoral veins can be isolated and a thrombus induced by a standardized pinch injury, the vein is transilluminated and thrombus image projected on to a screen enabling the dynamics of thrombus formation and Dr. Silvia Pierangeli, PhD