Steven Krilis

Steven Antony Krilis
AM
Born (1947-11-26) 26 November 1947
Athens, Greece
EducationUniversity of New South Wales; University of Sydney
Known forResearch on beta-2 glycoprotein I and antiphospholipid syndrome; Sydney classification criteria
AwardsMember of the Order of Australia; Corresponding Member of the Academy of Athens; honorary doctorate, National and Kapodistrian University of Athens
Scientific career
FieldsClinical immunology, autoimmunity, thrombosis, haemostasis, allergy, protein redox biology
WorkplacesUniversity of New South Wales; St George Hospital

Steven Antony Krilis AM (born 26 November 1947) is a Greek-born Australian physician-scientist, clinical immunologist and academic. He is a conjoint professor in the School of Clinical Medicine at the University of New South Wales (UNSW) and has served as head of the Department of Infectious Disease, Immunology and Sexual Health at St George Hospital, Sydney.[1] His research has addressed antiphospholipid syndrome (APS), beta-2 glycoprotein I (β2GPI), thrombosis, allergy, inflammation, innate immunity and the redox regulation of extracellular plasma proteins.[1]

Krilis and colleagues reported that autoimmune anticardiolipin-antibody binding required a plasma cofactor and subsequently purified and identified the cofactor as β2GPI.[2][3] This work contributed to a shift in APS research towards antibodies directed against phospholipid-binding plasma proteins. Subsequent studies by Krilis and collaborators investigated the structure and physiological functions of β2GPI in coagulation, innate immunity, vascular injury and extracellular redox regulation.

Krilis organised and chaired the 11th International Congress on Antiphospholipid Antibodies in Sydney in 2004. The associated international workshop revised the preliminary Sapporo classification criteria. The resulting consensus statement, published in 2006 with Spyridon Miyakis as first author and Krilis as senior author, became widely known as the Sydney classification criteria and was extensively used in APS research before publication of the 2023 ACR/EULAR criteria.[4][5]

Early life and education

Krilis was born in Athens on 26 November 1947 and emigrated to Australia in 1955.[6]

In 1972, Krilis, graduated with a Bachelor of Medicine and Bachelor of Surgery with honors (MBBS) from the University of New South Wales, Sydney Australia. In 1984, Krilis was awarded a PhD in Medicine from the University of Sydney, Australia. His PhD thesis identified the major allergen of the common house dust mite and generated monoclonal antibodies which he used to standardize house dust mite extracts.

In 1981, Krilis was awarded a National Health and Medical Research Council fellowship and a Fogarty International Postdoctoral Research Fellowship, to undertake post doctoral research at Harvard Medical School and Brigham and Women's Hospital.[6] with K. Frank Austen and Elias J. Corey, investigating sulfidopeptide leukotrienes.

Academic career

In November 1983, Krilis completed his Post Doctoral research and returned to Australia. In 1984, he became a post doctoral fellow at the Department of Medicine at St George Hospital, Kogarah, Australia. In 1990, he was appointed Professor of Medicine at the University of New South Wales. He held this position until 1993, when he became Director of the Department of Immunology, Allergy and Infectious Diseases and Sexual Health at St George Hospital .[7].[1]

[8]

Research

Leukotriene biology

During his Harvard postdoctoral work, Krilis contributed to studies of sulfidopeptide leukotrienes. In 1984, Krilis, Lewis, Corey and Austen reported a specific high-affinity receptor for leukotriene C4 in guinea-pig ileal smooth muscle and associated membrane fractions. The receptor's binding characteristics were consistent with mediation of the contractile response to leukotriene C4.[9]

Mast-cell biology

After returning to Australia in 1983, Krilis established a programme in human mast-cell biology. His laboratory investigated the differentiation and maturation of mast cells from human bone-marrow progenitors and factors regulating mast cells and basophils.[10][11] Later studies examined interleukin-16-responsive mast-cell and basophil progenitors and cytokine regulation of these cells.

β2-glycoprotein I and antiphospholipid syndrome

In 1989, Krilis and colleagues reported that autoimmune anticardiolipin-antibody binding depended on a plasma cofactor.[2] In 1990, they purified the cofactor and identified it as β2GPI, also known as apolipoprotein H.[3] Subsequent work from the laboratory investigated the structure, ligand binding and biological functions of β2GPI.

Structure and gene-targeted mice

Krilis and collaborators used mutagenesis and structural studies to identify regions of β2GPI involved in phospholipid binding, including basic residues in domain V.[12]

In 2001, Krilis and colleagues reported the first published gene-targeted β2GPI-deficient mouse model. Plasma from the deficient mice showed impaired thrombin generation.[13] An independently generated β2GPI-deficient mouse model was reported in 2025.[14]

Haemostasis and vascular injury

Krilis and colleagues showed that β2GPI binds coagulation factor XI and inhibits its activation by thrombin and factor XIIa.[15] The interaction was localised to domain V, which is cleaved by factor XIa.[16]

They also reported a redox-regulated interaction between β2GPI and von Willebrand factor, controlled by thioredoxin-1.[17] In murine thrombosis models, domain V mediated the antithrombotic effect of β2GPI.[18] Domain V also reduced natural IgM-mediated myocardial injury in a mouse model of cardiac ischaemia-reperfusion.[19]

Innate immunity

Experimental studies showed that β2GPI ameliorated Gram-negative bacterial inflammation and protected mice against Gram-negative septicaemia.[20][21]

Extracellular protein redox biology

Krilis and colleagues investigated reversible thiol-disulphide exchange in circulating proteins. They demonstrated redox-dependent regulation of β2GPI and its interaction with von Willebrand factor,[17] showed that factor XI is a substrate for oxidoreductases and that reduction enhances its activation,[22] and investigated redox forms of complement factor H and angiotensinogen.[1]

A case-control study using an enzyme-linked immunosorbent assay found lower free-thiol angiotensinogen in women with pre-eclampsia than in healthy pregnant controls.[23] The assay was later described as a method for quantifying total and free-thiol angiotensinogen.[24]

International leadership and classification criteria

Krilis organised and chaired the 11th International Congress on Antiphospholipid Antibodies in Sydney in 2004. The congress included an international workshop convened to revise the preliminary Sapporo classification criteria. The consensus statement was published in 2006 with Spyridon Miyakis, then a fellow in Krilis's department, as first author and Krilis as senior author.[4]

The Sydney criteria incorporated anti-β2GPI antibodies among the laboratory criteria, required persistent antibody positivity on tests at least 12 weeks apart, and refined aspects of the clinical classification of thrombotic and obstetric APS.[4] They were extensively used in APS research before the 2023 ACR/EULAR revision.[5]

Reviews

Krilis and Bill Giannakopoulos co-authored How I Treat the Antiphospholipid Syndrome in Blood in 2009.[25] In 2013 they published The Pathogenesis of the Antiphospholipid Syndrome in the New England Journal of Medicine.[26] Their 2024 review in Clinical Immunology examined the context-dependent functions of β2GPI domain V in health and disease.[27]

Honours and recognition

Krilis was appointed a Member of the Order of Australia in the 2019 Queen's Birthday Honours "for significant service to medical research in the areas of inflammation, thrombosis and allergic disease".[7]

In 2011, he received an honorary doctorate from the National and Kapodistrian University of Athens.[28]

In 2023, Krilis was elected a Corresponding Member of the Academy of Athens in the science of medicine, becoming the second Australian elected to the institution.[8]

Selected publications

  • McNeil, H. P.; Chesterman, C. N.; Krilis, S. A. (1989). "Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics". British Journal of Haematology. 73 (4): 506–513. doi:10.1111/j.1365-2141.1989.tb00289.x. PMID 2514785.
  • McNeil, H. P.; Simpson, R. J.; Chesterman, C. N.; Krilis, S. A. (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein I (apolipoprotein H)". Proceedings of the National Academy of Sciences of the United States of America. 87 (11): 4120–4124. Bibcode:1990PNAS...87.4120M. doi:10.1073/pnas.87.11.4120. PMC 54059. PMID 2349221.
  • Miyakis, S.; Lockshin, M. D.; Atsumi, T.; et al. (2006). "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)". Journal of Thrombosis and Haemostasis. 4 (2): 295–306. doi:10.1111/j.1538-7836.2006.01753.x. PMID 16420554.
  • Giannakopoulos, B.; Krilis, S. A. (2009). "How I treat the antiphospholipid syndrome". Blood. 114 (10): 2020–2030. doi:10.1182/blood-2009-05-220756. PMID 19587374.
  • Giannakopoulos, B.; Krilis, S. A. (2013). "The pathogenesis of the antiphospholipid syndrome". New England Journal of Medicine. 368 (11): 1033–1044. doi:10.1056/NEJMra1112830. PMID 23484830.

References

  1. 1 2 3 4 "Conjoint Professor Steven Krilis". University of New South Wales. Retrieved 20 July 2026.
  2. 1 2 McNeil, H. P.; Chesterman, C. N.; Krilis, S. A. (1989). "Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics". British Journal of Haematology. 73 (4): 506–513. doi:10.1111/j.1365-2141.1989.tb00289.x. PMID 2514785.
  3. 1 2 McNeil, H. P.; Simpson, R. J.; Chesterman, C. N.; Krilis, S. A. (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein I (apolipoprotein H)". Proceedings of the National Academy of Sciences of the United States of America. 87 (11): 4120–4124. Bibcode:1990PNAS...87.4120M. doi:10.1073/pnas.87.11.4120. PMC 54059. PMID 2349221.
  4. 1 2 3 Miyakis, S.; Lockshin, M. D.; Atsumi, T.; Branch, D. W.; Brey, R. L.; Cervera, R.; Derksen, R. H. W. M.; de Groot, P. G.; Koike, T.; Meroni, P. L.; Reber, G.; Shoenfeld, Y.; Tincani, A.; Vlachoyiannopoulos, P. G.; Krilis, S. A. (2006). "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)". Journal of Thrombosis and Haemostasis. 4 (2): 295–306. doi:10.1111/j.1538-7836.2006.01753.x. PMID 16420554.
  5. 1 2 Barbhaiya, M.; Zuily, S.; Naden, R.; Hendry, A.; Manneville, F.; Amigo, M.C.; Amoura, Z.; Andrade, D.; Andreoli, L.; Artim-Esen, B.; Atsumi, T.; Avcin, T.; Belmont, H.M.; Bertolaccini, M.L.; Branch, D.W.; Carvalheiras, G.; Casini, A.; Cervera, R.; Cohen, H.; Costedoat-Chalumeau, N.; Crowther, M.; de Jesus, G.; Delluc, A.; Desai, S.; De Sancho, M.; Devreese, K.M.; Diz-Kucukkaya, R.; Duarte-Garcia, A.; Frances, C.; Garcia, D.; Gris, J.C.; Jordan, N.; Leaf, R.K.; Kello, N.; Knight, J.S.; Laskin, C.; Lee, A.I.; Legault, K.; Levine, S.R.; Levy, R.A.; Limper, M.; Lockshin, M.D.; Mayer-Pickel, K.; Musial, J.; Meroni, P.L.; Orsolini, G.; Ortel, T.L.; Pengo, V.; Petri, M.; Pons-Estel, G.; Gomez-Puerta, J.A.; Raimboug, Q.; Roubey, R.; Sanna, G.; Seshan, S.V.; Sciascia, S.; Tektonidou, M.G.; Tincani, A.; Wahl, D.; Willis, R.; Yelnik, C.; Zuily, C.; Guillemin, F.; Costenbader, K.; Erkan, D. (2023). "2023 ACR/EULAR antiphospholipid syndrome classification criteria". Annals of the Rheumatic Diseases. 82 (10): 1258–1270. doi:10.1136/ard-2023-224609. PMID 37635643.
  6. 1 2 "Athens to Australia: Dr Aristidis Krilis into the Academy of Athens for outstanding medical contributions". Neos Kosmos. 30 April 2023. Retrieved 20 July 2026.
  7. 1 2 "Queen's Birthday 2019 Honours List: Member (AM) in the General Division of the Order of Australia, A-L" (PDF). Governor-General of Australia. 10 June 2019. Retrieved 20 July 2026.
  8. 1 2 "Greek Australian Steve Krilis elected member of the Academy of Athens". The Greek Herald. 3 May 2023. Retrieved 20 July 2026.
  9. ↑ Krilis, S.; Lewis, R. A.; Corey, E. J.; Austen, K. F. (1984). "Specific binding of leukotriene C4 to smooth muscle cells and evidence for a high-affinity receptor". Proceedings of the National Academy of Sciences of the United States of America. 81 (14): 4529–4533. doi:10.1073/pnas.81.14.4529. PMC 345643. PMID 6087330.
  10. ↑ Li, L.; Meng, X. W.; Krilis, S. (1996). "Mast cells expressing chymase but not tryptase can be derived by culturing human progenitors in conditioned medium obtained from a human mastocytosis cell strain with c-kit ligand". Journal of Immunology. 156 (12): 4839–4844. doi:10.4049/jimmunol.156.12.4839. PMID 8648136.
  11. ↑ Li, L.; Krilis, S. A. (1999). "Mast-cell growth and differentiation". Allergy. 54 (4): 306–312. doi:10.1034/j.1398-9995.1999.00086.x. PMID 10371088.
  12. ↑ Sheng, Y. H.; Sali, A.; Herzog, H.; Lahnstein, J.; Krilis, S. A. (1996). "Site-directed mutagenesis of recombinant human β2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anticardiolipin antibody cofactor activity". Journal of Immunology. 157 (8): 3744–3751. doi:10.4049/jimmunol.157.8.3744. PMID 8871678.
  13. ↑ Sheng, Y.; Reddel, S. W.; Herzog, H.; Wang, Y. X.; Brighton, T.; France, M. P.; Robertson, S. A.; Krilis, S. A. (2001). "Impaired thrombin generation in β2-glycoprotein I null mice". Journal of Biological Chemistry. 276 (17): 13817–13823. doi:10.1074/jbc.M010990200. PMID 11145969.
  14. ↑ Kulkarni, P.P.; Alluri, R.K.; Godwin, M.; Forbes, G.L.; Merkulova, A.; Lambert, S.; Vijay, A.; Palihati, M.; Kundu, S.; Shim, Y.J.; Kalonji, K.; Schmaier, A.H.; Holinstat, M.; Cameron, S.J.; McCrae, K.R. (2025). "Protection of beta2GPI-deficient mice from thrombosis reflects a defect in PAR3-facilitated platelet activation". Blood. 145 (18): 2086–2099. doi:10.1182/blood.2024024469. PMC 12105725. PMID 39869832.
  15. ↑ Shi, T.; Iverson, G. M.; Qi, J. C.; Cockerill, K. A.; Linnik, M. D.; Konecny, P.; Krilis, S. A. (2004). "Beta 2-glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: loss of inhibition by clipped beta 2-glycoprotein I". Proceedings of the National Academy of Sciences of the United States of America. 101 (11): 3939–3944. doi:10.1073/pnas.0400281101. PMC 374359. PMID 15007174.
  16. ↑ Shi, T.; Giannakopoulos, B.; Iverson, G. M.; Cockerill, K. A.; Linnik, M. D.; Krilis, S. A. (2005). "Domain V of beta2-glycoprotein I binds factor XI/XIa and is cleaved at Lys317-Thr318". Journal of Biological Chemistry. 280 (2): 907–912. doi:10.1074/jbc.M410291200. PMID 15522884.
  17. 1 2 Passam, F.H.; Rahgozar, S.; Qi, M.; et al. (2010). "Redox control of β2-glycoprotein I-von Willebrand factor interaction by thioredoxin-1". Journal of Thrombosis and Haemostasis. 8 (8): 1754–1762. doi:10.1111/j.1538-7836.2010.03944.x. PMC 3017748. PMID 20979592.
  18. ↑ Passam, F. H.; Chen, G.; Chen, V. M.; Qi, M.; Krilis, S. A.; Giannakopoulos, B. (2022). "Βeta-2-glycoprotein I exerts antithrombotic function through its domain V in mice". Journal of Autoimmunity. 126 102747. doi:10.1016/j.jaut.2021.102747. PMID 34794103.
  19. ↑ Zhang, P.; Weaver, J.C.; Chen, G.; Beretov, J.; Atsumi, T.; Qi, M.; Bhindi, R.; Qi, J.C.; Madigan, M.C.; Giannakopoulos, B.; Krilis, S.A. (2016). "The fifth domain of beta 2 glycoprotein I protects from natural IgM mediated cardiac ischaemia reperfusion injury". PLOS ONE. 11 (3) e0152681. Bibcode:2016PLoSO..1152681Z. doi:10.1371/journal.pone.0152681. PMC 4816326. PMID 27031114.
  20. ↑ Zhou, S.; Chen, G.; Qi, M.; et al. (2016). "Gram negative bacterial inflammation ameliorated by the plasma protein beta 2-glycoprotein I". Scientific Reports. 6 33656. Bibcode:2016NatSR...633656Z. doi:10.1038/srep33656. PMC 5036083. PMID 27670000.
  21. ↑ El-Assaad, F.; Qi, M.; Gordon, A.K.; et al. (2017). "Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner". Scientific Reports. 7 (1): 8201. Bibcode:2017NatSR...7.8201E. doi:10.1038/s41598-017-07945-8. PMC 5559448. PMID 28811580.
  22. ↑ Giannakopoulos, B.; Gao, L.; Qi, M.; et al. (2012). "Factor XI is a substrate for oxidoreductases: enhanced activation of reduced FXI and its role in antiphospholipid syndrome thrombosis". Journal of Autoimmunity. 39 (3): 121–129. doi:10.1016/j.jaut.2012.05.005. PMID 22704541.
  23. ↑ Rahgozar, S.; Amirian, T.; Qi, M.; et al. (2015). "Improved assay for quantifying a redox form of angiotensinogen as a biomarker for pre-eclampsia: a case-control study". PLOS ONE. 10 (8) e0135905. Bibcode:2015PLoSO..1035905R. doi:10.1371/journal.pone.0135905. PMC 4552701. PMID 26312482.
  24. ↑ Qi, M.; Weaver, J. C.; Rahgozar, S.; Giannakopoulos, B.; Krilis, S. A. (2019). "Quantitation of total and free thiol angiotensinogen as a prognostic marker for preeclampsia". Functional Disulphide Bonds. Methods in Molecular Biology. Vol. 1967. pp. 285–293. doi:10.1007/978-1-4939-9187-7_18. ISBN 978-1-4939-9186-0. PMID 31069778.
  25. ↑ Giannakopoulos, B.; Krilis, S. A. (2009). "How I treat the antiphospholipid syndrome". Blood. 114 (10): 2020–2030. doi:10.1182/blood-2009-05-220756. PMID 19587375.
  26. ↑ Giannakopoulos, B.; Krilis, S. A. (2013). "The pathogenesis of the antiphospholipid syndrome". New England Journal of Medicine. 368 (11): 1033–1044. doi:10.1056/NEJMra1112830. PMID 23484830.
  27. ↑ Giannakopoulos, B.; Krilis, S. A. (2024). "Domain 5 of Beta 2 glycoprotein I: Friend or foe in health? Context matters". Clinical Immunology. 265 110282. doi:10.1016/j.clim.2024.110282. PMID 38917928.
  28. ↑ "National and Kapodistrian University of Athens annual report, 2010–2012" (PDF) (in Greek). National and Kapodistrian University of Athens. Retrieved 20 July 2026.
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