Interrelation of T Cell Cytokines and Autoantibodies in Systemic Lupus Erythematosus: A Cross-sectional Study

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2023 Jan 22

PMID 36682593

Authors

Fatima K Alduraibi

Kathryn A Sullivan

W Winn Chatham

Hui-Chen Hsu

John D Mountz

Affiliations

Soon will be listed here.

Abstract

T-helper cytokines interferon gamma (IFNɣ), interleukin 17 (IL-17) and IL-10 impact systemic lupus erythematosus (SLE) directly and indirectly via modulation of autoAb production. We determined the separate and combined effects on clinical manifestations of SLE (N = 62). IFNɣ, IL-17 but not IL-10 were significantly elevated in patients with SLE. IFNɣ positively correlated with anti-DNA and anti-SSA. IL-17 positively correlated with anti-SSA and was significantly higher in patients with discoid rash and class V LN. IL-10 did not correlate with circulating autoantibodies but was significantly elevated in patients with LN. Patients with LN had elevated plasma levels of anti-DNA and anti-Sm/ribonuclear protein (RNP). Anti-Sm/RNP levels were decreased in patients with acute mucocutaneous manifestations, including photosensitivity and/or malar rash. The study provides critical insights into pathological mechanisms of LN, which could help guide future diagnoses and therapies.

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References

Munroe M, Lu R, Zhao Y, Fife D, Robertson J, Guthridge J . Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann Rheum Dis. 2016; 75(11):2014-2021. PMC: 4959992. DOI: 10.1136/annrheumdis-2015-208140. View

Zeid S, Khalifa G, Nabil M . IL10 in Lupus Nephritis: Detection and relationship with disease activity. Electron Physician. 2016; 7(8):1680-5. PMC: 4725424. DOI: 10.19082/1680. View

Mason L, Isenberg D . Immunopathogenesis of SLE. Baillieres Clin Rheumatol. 1999; 12(3):385-403. DOI: 10.1016/s0950-3579(98)80026-5. View

Bombardier C, Gladman D, Urowitz M, Caron D, Chang C . Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992; 35(6):630-40. DOI: 10.1002/art.1780350606. View

Blenman K, Duan B, Xu Z, Wan S, Atkinson M, Flotte T . IL-10 regulation of lupus in the NZM2410 murine model. Lab Invest. 2006; 86(11):1136-48. DOI: 10.1038/labinvest.3700468. View

Uhm W, Na K, Song G, Jung S, Lee T, Park M . Cytokine balance in kidney tissue from lupus nephritis patients. Rheumatology (Oxford). 2003; 42(8):935-8. DOI: 10.1093/rheumatology/keg255. View

Hochberg M . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997; 40(9):1725. DOI: 10.1002/art.1780400928. View

Cui H, Qi Z, Yang L, Qi L, Zhang N, Zhang X . Interleukin-10 receptor expression and signalling were down-regulated in CD4⁺ T cells of lupus nephritis patients. Clin Exp Immunol. 2011; 165(2):163-71. PMC: 3142641. DOI: 10.1111/j.1365-2249.2011.04424.x. View

Balow J . Clinical presentation and monitoring of lupus nephritis. Lupus. 2005; 14(1):25-30. DOI: 10.1191/0961203305lu2055oa. View

10.

Chen Y, Chauhan S, Shao C, Omoto M, Inomata T, Dana R . IFN-γ-Expressing Th17 Cells Are Required for Development of Severe Ocular Surface Autoimmunity. J Immunol. 2017; 199(3):1163-1169. PMC: 5526719. DOI: 10.4049/jimmunol.1602144. View

11.

Janwityanuchit S, Verasertniyom O, Vanichapuntu M, Vatanasuk M . Anti-Sm: its predictive value in systemic lupus erythematosus. Clin Rheumatol. 1993; 12(3):350-3. DOI: 10.1007/BF02231577. View

12.

Pisetsky D, Lipsky P . New insights into the role of antinuclear antibodies in systemic lupus erythematosus. Nat Rev Rheumatol. 2020; 16(10):565-579. PMC: 8456518. DOI: 10.1038/s41584-020-0480-7. View

13.

Chun H, Chung J, Kim H, Yun J, Jeon J, Ye Y . Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007; 27(5):461-6. DOI: 10.1007/s10875-007-9104-0. View

14.

Miyake K, Akahoshi M, Nakashima H . Th subset balance in lupus nephritis. J Biomed Biotechnol. 2011; 2011:980286. PMC: 3163408. DOI: 10.1155/2011/980286. View

15.

Li H, Adamopoulos I, Moulton V, Stillman I, Herbert Z, Moon J . Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells. Nat Commun. 2020; 11(1):2859. PMC: 7275084. DOI: 10.1038/s41467-020-16636-4. View

16.

Wu Y, Hsing C, Chiu C, Huang H, Hsu Y . Roles of IL-1 and IL-10 family cytokines in the progression of systemic lupus erythematosus: Friends or foes?. IUBMB Life. 2021; 74(2):143-156. DOI: 10.1002/iub.2568. View

17.

Geginat J, Vasco M, Gerosa M, Tas S, Pagani M, Grassi F . IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus. Semin Immunol. 2019; 44:101330. DOI: 10.1016/j.smim.2019.101330. View

18.

Mizui M, Koga T, Lieberman L, Beltran J, Yoshida N, Johnson M . IL-2 protects lupus-prone mice from multiple end-organ damage by limiting CD4-CD8- IL-17-producing T cells. J Immunol. 2014; 193(5):2168-77. PMC: 4135016. DOI: 10.4049/jimmunol.1400977. View

19.

Hartman E, Royen-Kerkhof A, Jacobs J, Welsing P, Fritsch-Stork R . Performance of the 2012 Systemic Lupus International Collaborating Clinics classification criteria versus the 1997 American College of Rheumatology classification criteria in adult and juvenile systemic lupus erythematosus. A systematic review and.... Autoimmun Rev. 2018; 17(3):316-322. DOI: 10.1016/j.autrev.2018.01.007. View

20.

Bagavant H, Fu S . Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol. 2009; 21(5):489-94. PMC: 2841319. DOI: 10.1097/BOR.0b013e32832efff1. View