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George Bertsias

George Bertsias

Assistant Professor, Univ. of Crete
Email address
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Phone
+30-2810-394635
Fax
+30-2810-394871

The Laboratory of Rheumatology, Autoimmunity and Inflammation together with the Affiliated Clinical Research Unit at the University Hospital, represent an interdisciplinary group of physician scientists, bio-scientists, clinicians and nurses that investigates medical inflammation in the context of autoinflammatory-autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and familial Mediterranean fever.

The laboratory explores mechanisms of breakdown of immune tolerance, tissue injury and repair with the ultimate goal of developing novel therapies. We use animal models as well as human tissues to investigate innate and adaptive immune responses under the premise that they share common effector pathways for tissue injury. Importantly, we utilize well-characterized patient cohorts and biorepositories seeking to identify molecular biomarkers for diagnosis and monitoring. We seek to explore molecular or genetic biomarkers that predict response or toxicity to therapy. We participate in local and international consortia in the context of competitive translational research projects.

The Systemic Autoimmunity and Gene Regulation Unit focuses on the study of immune regulation by costimulatory receptors, inflammatory cytokines and cellular metabolic pathways using SLE as a disease-model. We apply high-throughput technologies in tissues from selected patient groups in order to delineate the genomic/epigenetic basis of specific phenotypes (such as gender bias) or outcomes (response or failure to treatments) of the disease.

Gkirtzimanaki K, Kabrani E, Nikoleri D, Polyzos A, Blanas A, Sidiropoulos P, Makrigiannakis A, Bertsias G, Boumpas DT, Verginis P. (2018) IFNα Impairs Autophagic Degradation of mtDNA Promoting Autoreactivity of SLE Monocytes in a STING-Dependent Fashion. Cell Rep. 25:921-933.e5

Gergianaki I, Fanouriakis A, Repa A, Tzanakakis M, Adamichou C, Pompieri A, Spirou G, Bertsias A, Kabouraki E, Tzanakis I, Chatzi L, Sidiropoulos P, Boumpas DT, Bertsias GK. (2017) Epidemiology and burden of systemic lupus erythematosus in a Southern European population: data from the community-based lupus registry of Crete, Greece. Ann Rheum Dis. 76:1992-2000.

Krasoudaki E, Banos A, Stagakis E, Loupasakis K, Drakos E, Sinatkas V, Zampoulaki A, Papagianni A, Iliopoulos D, Boumpas DT, Bertsias GK. (2016) Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4. Nephrol Dial Transplant. 31:1676-86.

Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I, Seyahi E, Ozyazgan Y, Sacli FS, Erer B, Inoko H, Emrence Z, Cakar A, Abaci N, Ustek D, Satorius C, Ueda A, Takeno M, Kim Y, Wood GM, Ombrello MJ, Meguro A, Gul A, Remmers EF, Kastner DL. (2013) Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1. Nat Genet. 45:202-7.

Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, Iliopoulos D, Boumpas DT. (2011) Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis. 70:1496-506.

1. Papadimitraki ED, Choulaki C, Koutala E, et al. Expansion of toll-like receptor 9-expressing B cells in active systemic lupus erythematosus: implications for the induction and maintenance of the autoimmune process. Arthritis Rheum 2006;54:3601-11.

2. Karvounaris SA, Sidiropoulos PI, Papadakis JA, et al. Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study. Ann Rheum Dis 2007;66:28-33.

3. Bertsias G, Gordon C, Boumpas DT. Clinical trials in systemic lupus erythematosus (SLE): lessons from the past as we proceed to the future--the EULAR recommendations for the management of SLE and the use of end-points in clinical trials. Lupus 2008;17:437-42.

4. Bertsias G, Ioannidis JP, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008;67:195-205.

5. Nakou M, Knowlton N, Frank MB, et al. Gene expression in systemic lupus erythematosus: bone marrow analysis differentiates active from inactive disease and reveals apoptosis and granulopoiesis signatures. Arthritis Rheum 2008;58:3541-9.

6. Bertsias GK, Nakou M, Choulaki C, et al. Genetic, immunologic, and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosus. Arthritis Rheum 2009;60:207-18.

7. Nakou M, Katsikas G, Sidiropoulos P, et al. Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis Res Ther 2009;11:R131.

8. Papadimitraki ED, Tzardi M, Bertsias G, Sotsiou E, Boumpas DT. Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response. Lupus 2009;18:831-5.

9. Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol 2010;6:358-67.

10. Bertsias GK, Ioannidis JP, Aringer M, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010;69:2074-82.

11. Bertsias GK, Salmon JE, Boumpas DT. Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade. Ann Rheum Dis 2010;69:1603-11.

12. Nakou M, Bertsias G, Stagakis I, et al. Gene network analysis of bone marrow mononuclear cells reveals activation of multiple kinase pathways in human systemic lupus erythematosus. PLoS One 2010;5:e13351.

13. Raptopoulou AP, Bertsias G, Makrygiannakis D, et al. The programmed death 1/programmed death ligand 1 inhibitory pathway is up-regulated in rheumatoid synovium and regulates peripheral T cell responses in human and murine arthritis. Arthritis Rheum 2010;62:1870-80.

14. Bertsias GK, Boumpas DT. Connective tissue diseases: Lupus nephritis-winning a few battles but not the war. Nat Rev Rheumatol 2011;7:441-2.

15. Fanouriakis A, Boumpas DT, Bertsias GK. Balancing efficacy and toxicity of novel therapies in systemic lupus erythematosus. Expert Rev Clin Pharmacol 2011;4:437-51.

16. Kourbeti IS, Papadakis JA, Neophytou C, et al. Infections in patients with traumatic brain injury who undergo neurosurgery. Br J Neurosurg 2011;25:9-15.

17. Ntali S, Bertsias G, Boumpas DT. Cyclophosphamide and lupus nephritis: when, how, for how long? Clin Rev Allergy Immunol 2011;40:181-91.

18. Perysinaki GS, Moysiadis DK, Bertsias G, et al. Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology. Lupus 2011;20:781-91.

19. Stagakis E, Bertsias G, Verginis P, et al. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis 2011;70:1496-506.

20. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012;71:1771-82.

21. Moysiadis DK, Perysinaki GS, Bertsias G, et al. Early treatment with glucocorticoids or cyclophosphamide retains the slit diaphragm proteins nephrin and podocin in experimental lupus nephritis. Lupus 2012;21:1196-207.

22. Stagakis I, Bertsias G, Karvounaris S, et al. Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther 2012;14:R141.

23. Bertsias GK, Pamfil C, Fanouriakis A, Boumpas DT. Diagnostic criteria for systemic lupus erythematosus: has the time come? Nat Rev Rheumatol 2013;9:687-94.

24. Fanouriakis A, Boumpas DT, Bertsias GK. Pathogenesis and treatment of CNS lupus. Curr Opin Rheumatol 2013;25:577-83.

25. Frangou EA, Bertsias GK, Boumpas DT. Gene expression and regulation in systemic lupus erythematosus. Eur J Clin Invest 2013;43:1084-96.

26. Kirino Y, Bertsias G, Ishigatsubo Y, et al. Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1. Nat Genet 2013;45:202-7.

27. Nakou M, Papadimitraki ED, Fanouriakis A, et al. Interleukin-21 is increased in active systemic lupus erythematosus patients and contributes to the generation of plasma B cells. Clin Exp Rheumatol 2013;31:172-9.

28. van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 2014;73:958-67.

29. Choulaki C, Papadaki G, Repa A, et al. Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis. Arthritis Res Ther 2015;17:257.

30. Pamfil C, Fanouriakis A, Damian L, et al. EULAR recommendations for neuropsychiatric systemic lupus erythematosus vs usual care: results from two European centres. Rheumatology (Oxford) 2015;54:1270-8.

31. Bertsias G, Karampli E, Sidiropoulos P, et al. Clinical and financial burden of active lupus in Greece: a nationwide study. Lupus 2016;25:1385-94.

32. Fanouriakis A, Pamfil C, Rednic S, Sidiropoulos P, Bertsias G, Boumpas DT. Is it primary neuropsychiatric systemic lupus erythematosus? Performance of existing attribution models using physician judgment as the gold standard. Clin Exp Rheumatol 2016;34:910-7.

33. Krasoudaki E, Banos A, Stagakis E, et al. Micro-RNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4. Nephrol Dial Transplant 2016;31:1676-86.

34. Papadaki G, Kambas K, Choulaki C, et al. Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation. Eur J Immunol 2016;46:2542-54.

35. Simos P, Ktistaki G, Dimitraki G, et al. Cognitive deficits early in the course of rheumatoid arthritis. J Clin Exp Neuropsychol 2016;38:820-9.

36. Vlachou K, Mintzas K, Glymenaki M, et al. Elimination of Granulocytic Myeloid-Derived Suppressor Cells in Lupus-Prone Mice Linked to Reactive Oxygen Species-Dependent Extracellular Trap Formation. Arthritis Rheumatol 2016;68:449-61.

37. Wilhelmus S, Bajema IM, Bertsias GK, et al. Lupus nephritis management guidelines compared. Nephrol Dial Transplant 2016;31:904-13.

38.  Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis 2017;76:476-85.

39. Bortoluzzi A, Fanouriakis A, Appenzeller S, et al. Validity of the Italian algorithm for the attribution of neuropsychiatric events in systemic lupus erythematosus: a retrospective multicentre international diagnostic cohort study. BMJ Open 2017;7:e015546.

40. Gergianaki I, Fanouriakis A, Repa A, et al. Epidemiology and burden of systemic lupus erythematosus in a Southern European population: data from the community-based lupus registry of Crete, Greece. Ann Rheum Dis 2017;76:1992-2000.

41. Karademas EC, Ktistaki G, Dimitraki G, et al. Patient and partner dispositional optimism as a long-term predictor of illness representations in autoimmune diseases. J Health Psychol 2017;22:1691-700.

42. van Vollenhoven R, Voskuyl A, Bertsias G, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis 2017;76:554-61.

43. Adamichou C, Georgakis S, Bertsias G. Cytokine targets in lupus nephritis: Current and future prospects. Clin Immunol 2018.

44. Bolaki M, Karagiannis K, Bertsias G, Mitrouska I, Tzanakis N, Antoniou KM. New respiratory symptoms and lung imaging findings in a woman with polymyositis. Breathe (Sheff) 2018;14:e34-e9.

45. Boumpas DT, Bertsias GK, Fanouriakis A. 2008-2018: a decade of recommendations for systemic lupus erythematosus. Ann Rheum Dis 2018;77:1547-8.

46. Christou EAA, Banos A, Kosmara D, Bertsias GK, Boumpas DT. Sexual dimorphism in SLE: above and beyond sex hormones. Lupus 2018:961203318815768.

47. Fanouriakis A, Adamichou C, Koutsoviti S, et al. Low disease activity-irrespective of serologic status at baseline-associated with reduction of corticosteroid dose and number of flares in patients with systemic lupus erythematosus treated with belimumab: A real-life observational study. Semin Arthritis Rheum 2018;48:467-74.

48. Fanouriakis A, Papalopoulos I, Gergianaki I, et al. In early arthritis patients, high HAQ at baseline and DAS28 at three months predict suboptimal outcomes at two years: a retrospective cohort study. Clin Exp Rheumatol 2018;36:806-13.

49. Gergianaki I, Bertsias G. Systemic Lupus Erythematosus in Primary Care: An Update and Practical Messages for the General Practitioner. Front Med (Lausanne) 2018;5:161.

50. Gergianaki I, Bortoluzzi A, Bertsias G. Update on the epidemiology, risk factors, and disease outcomes of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2018;32:188-205.

51. Gkirtzimanaki K, Kabrani E, Nikoleri D, et al. IFNalpha Impairs Autophagic Degradation of mtDNA Promoting Autoreactivity of SLE Monocytes in a STING-Dependent Fashion. Cell Rep 2018;25:921-33 e5.

52. Leuchten N, Bertsias G, Smolen J, et al. ANA as an Entry Criterion in SLE Classification. Arthritis Care Res (Hoboken) 2018.

53. Papadaki E, Fanouriakis A, Kavroulakis E, et al. Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus. Ann Rheum Dis 2018;77:441-8.