Lupus is a chronic and varied autoimmune disease in which the immune system creates antibodies that react not just against intruders, but also toward the body. These “flares” of inflammation cause pain and, oftentimes, injury to organs.
In the last 50 years, only one new treatment—belimumab—has been approved for treatment of lupus. Why? Because the disease is incredibly complex and different in each patient, ranging from mild to severe, though it can grow more destructive with time. In the clinic, we are interested in optimizing lupus clinical trial design and creating better measures of lupus disease activity and response.
One promising new treatment for lupus is dipyridamole, a medication extensively used in combination with aspirin for stroke prevention. Shown to inhibit certain lymphocyte populations that are over-reactive in lupus, dipyridamole delays the emergence of lupus-related pathology in mice with lupus. We are interested in investigating the efficacy of dipyridamole in preventing lupus flares and its impact on biomarkers of disease activity.
Another focus of our research will be the vagus nerve. It’s known that the nervous system can inhibit the production of antibodies through the vagus nerve and that heart rate variability (or HRV) can be used to measure vagus nerve activity in humans. We are interested in investigating the relationship of HRV to lupus disease activity over time.
Despite a plethora of promising treatments for systemic lupus erythematosus (SLE) reaching early phase clinical studies, none except belimumab has been able to show superiority in large trials and thus become available to patients. Attempts to explain this failure have pointed (among other pitfalls) to the use of problematic clinical endpoints. Lupus clinical outcome measures are sometimes organ focused (e.g. renal response definitions, CLASI, each individual domain of the BILAG index). Alternatively global scores have been used [SELENA-SLEDAI, SELENA-SLEDAI flare index, global BILAG, BILAG flare index, SLE responder index (SRI), BILAG-based Composite Lupus Assessment (BICLA)]. Much remains to be learned about the comparative performance of these endpoints, particularly the composite indices of SRI and BICLA. We have been interested in exploring the relative utility of these measures in relation to patients’ clinical phenotype and biologic signature (cytokine levels, gene expression patterns).
T cells in systemic lupus express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. We are investigating the efficacy of dipyridamole in the prevention of lupus flares and its impact on T and B cell biomarkers in this population.
Systemic lupus erythematosus is characterized by deregulation of cytokine pathways that bridge innate and adaptive immunity. Production of inflammatory cytokines by macrophages and other immune cells, can be physiologically inhibited by neural signals through the vagus nerve, a process termed the cholinergic anti-inflammatory pathway. Heart rate variability (HRV), an easily obtainable electrocardiographic measure of vagus nerve activity, has been inversely correlated with inflammatory markers in the general population. Decreases in HRV have been demonstrated in a broad array of pathologic conditions, including lupus. The relationship however between HRV and disease activity in lupus patients has not been conclusively examined. We are interested in investigating the relation of HRV with lupus disease activity over time, as reflected on clinical indices and on patterns of cytokine pathway activation.
M.D., University of Athens Medical School, Athens, Greece, 2002
B.S., Aristotle University of Thessaloniki, Greece, 1997
Honors and Awards
2009 ACP 2nd Clinical Vignette Award, Oklahoma Chapter Scientific Meeting, Oklahoma City, OK
2008 Trainee Research Award, Southern Society for Clinical Investigation Annual Meeting, New Orleans, LA
2000-2002 “Papadakis” Scholarship for Medical Studies, University of Athens
Joined OMRF Scientific Staff in 2012
Thanou A, Merrill JT. New Trials in Lupus and where Are we Going. Curr Rheumatol Rep. 2018 May 3; 20(6):34. Review. PMID: 29725880
Merrill JT, Immermann F, Whitley M, Zhou T, Hill A, O'Toole M, Reddy P, Honczarenko M, Thanou A, Rawdon J, Guthridge JM, James JA, Sridharan S. The Biomarkers of Lupus Disease Study: A Bold Approach May Mitigate Interference of Background Immunosuppressants in Clinical Trials. Arthritis Rheumatol. 2017 Jun; 69(6):1257-1266. PMID: 28257602
Thanou A, Stavrakis S, Dyer JW, Munroe ME, James JA, Merrill JT. Impact of heart rate variability, a marker for cardiac health, on lupus disease activity. Arthritis Res Ther. 2016 Sep 2; 18:197. PMID: 27590046
Thanou A, Merrill JT. Top 10 things to know about lupus activity measures. Curr Rheumatol Rep 15:334, 2013. [Abstract]
Thanou-Stavraki A, Sawalha AH. An update on Belimumab for the treatment of lupus. Biologics 5:33-43, 2011. [Abstract]
Thanou-Stavraki A, Sawalha AH, Crowson AN, Harley JB. Noodling and Mycobacterium marinum infection mimicking seronegative rheumatoid arthritis complicated by anti-tumor necrosis factor alpha therapy. Arthritis Care Res (Hoboken) 63:160-164, 2011. [Abstract]
Thanou-Stavraki A, Aberle T, Aksentijevich I, Bane BL, Harley JB. Clarithromycin in adult-onset Still's disease: a potentially useful therapeutic. J Clin Rheumatol 17:373-376, 2011. [Abstract]
Thanou-Stavraki A, James JA. Primary Sjogren's syndrome: current and prospective therapies. Semin Arthritis Rheum 37:273-292, 2008. [Abstract]
Tiniakos D, Thanou A, Kittas CH. Amyloidosis of the liver. Hellenic Arch Pathol 19:13-23, 2005. [Abstract]
Arthritis & Clinical Immunology Research Program, MS 22
Oklahoma Medical Research Foundation
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