These findings contributed to the development of the first lupus prevention trial, the Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE). This multi-center, randomized, placebo-controlled, double-blind, parallel group, 36-month clinical trial will evaluate the efficacy and safety of hydroxychloroquine intervention to prevent autoantibody accrual and future onset of clinically apparent SLE. SMILE will enroll 120 patients who are ANA positive and have at least one clinical lupus criterion, testing whether a high-risk soluble mediator score, genetic risk score or some combination best predicts who will transition to lupus. SMILE is now recruiting patients.
“We are testing whether we can slow progression to lupus, or if we can decrease the number of autoantibodies. We’re also testing some of these high-risk soluble mediator scores identified in other cohorts to see if we can identify who will or won’t transition, and we’re looking at the total genetic load using data from recent trials,” said Dr. James.
Clinical rheumatologists who receive questions about lupus risk from family members should stress that most relatives will not transition to disease. “If you have family members who are really stressed about whether they will develop lupus, or if they have a positive ANA or some clinical feature, we can share lifestyle choices that may help them, based on data that these may be associated with lupus transition and are good ideas for your health anyway,” such as quitting smoking, getting adequate sleep, ensuring adequate vitamin D levels and maintaining ideal body weight, she concluded.
Susan Bernstein is a freelance journalist based in Atlanta.
References
- Harley JB, James JA. Epstein-Barr virus infection induces lupus autoimmunity. Bull NYU Hosp Jt Dis. 2006;64(1–2):45–50.
- Heinlen LD, McClain MT, Merrill J, et al. Clinical criteria for systemic lupus erythematosus precede diagnosis and associated autoantibodies are present before clinical symptoms. Arthritis Rheum. 2007 Jul;56(7):2344–2351.
- Arbuckle MR, James JA, Dennis GJ, et al. Rapid clinical progression to diagnosis among African-American men with systemic lupus erythematosus. Lupus. 2003;12(2):99–105.
- McClain MT, Arbuckle MR, Heinlen LD, et al. The prevalence, onset and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus. Arthritis Rheum. 2004 Apr;50(4):1226–1232.
- Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. New Engl J Med. 2003 Oct 16;349:1526–1533.
- Munroe ME, Lu R, Zhao YD, et al. Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann Rheum Dis. 2016 Nov;75(11):2014–2021.
- Slight-Webb S, Bourn RL, Holers VM, et al. Shared and unique immune alterations in pre-clinical autoimmunity. Curr Opin Immunol. 2019 Dec;61:60–68.
- Barbhaiya M, Lu B, Sparks JA, et al. Influence of alcohol consumption on the risk of systemic lupus erythematosus among women in the Nurses’ Health Study cohorts. Arthritis Care Res (Hoboken). 2017 Mar;69(3):384–392.
- Roberts AL, Kubzansky LD, Malspeis S, et al. Association of depression with risk of incident systemic lupus erythematosus in women assessed across two decades. JAMA Psychiatry. 2018 Dec 1;75(12):1225–1233.
- James JA, Chen H, Young KA, et al. Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients. EBioMedicine. 2019 Apr;42:76–85.
- Munroe ME, Young KA, Kamen DL, et al. Soluble mediators and clinical features discern risk of transitioning to classified disease in relatives of systemic lupus erythematosus patients. Arthritis Rheumatol. 2017 Mar;69(3):630–643.
- Jog NR, Young KA, Munroe ME, et al. Association of Epstein-Barr virus serological reactivation with transitioning to systemic lupus erythematosus in at-risk individuals. Ann Rheum Dis. 2019 Sep;78(9):1235–1241.
- Young KA, Munroe ME, Guthridge JM, et al. Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus. Ann Rheum Dis. 2017 Jan;76(1):153–158.
- Young KA, Munroe ME, Harley JB, et al. Less than seven hours of sleep per night is associated with transitioning to systemic lupus erythematosus. Lupus. 2018 Aug;27(9):1524–1531.
- Slight-Webb S, Lu R, Rittenhouse LL, et al. Autoantibody-positive healthy individuals display unique immune profiles that may regulate autoimmunity. Arthritis Rheumatol. 2016 Oct;68(10):2492–2502.
- Ochs RL, Mahler M, Basu A, et al. The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: Integrating basic science with clinical understanding. Clin Exp Med. 2016 Aug;16(3):273–293.
- Carter JB, Carter S, Saschenbrecker S, et al. Recognition and relevance of anti-DFS70 autoantibodies in routine antinuclear autoantibodies testing at a community hospital. Front Med (Lausanne). 2018 Apr 9;5:88.
- James JA, Kim-Howard XR, Bruner BF, et al. Hydroxychloroquine sulfate treatment is associated with later onset of systemic lupus erythematosus. Lupus. 2007;16(6):401–409.