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. 2023 Feb:247:109239.
doi: 10.1016/j.clim.2023.109239. Epub 2023 Jan 20.

Interrelation of T cell cytokines and autoantibodies in systemic lupus erythematosus: A cross-sectional study

Fatima K Alduraibi  1 , Kathryn A Sullivan  2 , W Winn Chatham  2 , Hui-Chen Hsu  2 , John D Mountz  3
Affiliations

Interrelation of T cell cytokines and autoantibodies in systemic lupus erythematosus: A cross-sectional study

Fatima K Alduraibi et al. Clin Immunol. 2023 Feb.

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.

Keywords: Interferon gamma; Interleukin 10; Interleukin 17; Lupus nephritis; Systemic lupus erythematosus.

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Conflict of interest statement

Declaration of Competing Interest None. The authors declare that there is no conflict of interest.

Figures

Fig. 1.
Fig. 1.. Elevation of cytokines and autoantibodies in patients with SLE.
Plasma levels of cytokines and autoantibodies in healthy control (HC) subjects and patients with SLE were measured by ELISA. (A) Bar graph shows the levels of IFNγ, IL-17, and IL10. (B) Bar graph shows the levels of anti-DNA, anti-SSA, and anti-Sm/RNP in healthy control subjects and patients with SLE (data are presented as the mean ± SEM; unpaired t-test, with p-value shown at the top and the number of patients in each category shown at the bottom of each panel). SLE, systemic lupus erythematosus; IFNγ, interferon gamma; IL, interleukin; ELISA, enzyme-linked immunosorbent assay; SEM, standard error of the mean.
Fig. 2.
Fig. 2.. IL-10 is elevated in patients with LN and IL-17 is elevated in patients with class V LN.
Plasma levels of IFNɣ, IL-17, and IL-10 were measured by ELISA. (A) Bar graph shows the levels of IFNγ, IL-17, and IL-10 in patients with (+) or without (−) LN. (B) Bar graph shows the levels of IFNγ, IL-17, and IL-10 in patients who developed class III or IV LN, compared to the levels in patients who developed class V LN (data are presented as the mean ± SEM; unpaired t-test, with p-value shown at the top and the number of patients in each category shown at the bottom of each panel). SLE, systemic lupus erythematosus; IFNγ, interferon gamma; IL, interleukin; ELISA, enzyme-linked immunosorbent assay; LN, lupus nephritis; SEM, standard error of the mean.
Fig. 3.
Fig. 3.. Elevation of anti-DNA and anti-Sm/RNP antibodies in patients with LN.
Plasma levels of IgG anti-DNA, anti-SSA, and anti-Sm/RNP were determined by ELISA. (A) Bar graph shows the levels of anti-DNA, anti-SSA, and anti-Sm/RNP in patients with (+) or without (−) LN. (B) Bar graph shows the levels of anti-DNA, anti-SSA, and anti-Sm/RNP in patients who developed class III or IV LN, compared to the levels in patients who developed class V LN (data are presented as the mean ± SEM; unpaired t-test, with p-value shown at the top and the number of patients in each category shown at the bottom of each panel). ELISA, enzyme-linked immunosorbent assay; LN, lupus nephritis; SEM, standard error of the mean.
Fig. 4.
Fig. 4.. Anti-DNA positively correlates with IFNγ and anti-SSA positively correlates with IFNγ and IL-17.
(A) Regression analysis showing the correlation among circulating levels of IFNɣ, IL-17, and IL-10. (B–D) Regression analysis showing the correlation of circulating levels of autoantibodies with IFNγ (B), IL-17 (C), and IL-10 (D). All analyses were carried out using linear regression. The R2, p-value, and number of subjects for each set of comparisons are shown on the plot. IFNγ, interferon gamma; IL, interleukin.
Fig. 5.
Fig. 5.. Increased plasma levels of IL-17 in patients with DLE.
(A–D) Bar graphs show the levels of IFNγ, IL-17, and IL-10 in patients with (positive) or without (negative) arthritis (A), ACLE (B), DLE (C), and serositis (D) (data are presented as the mean ± SEM; unpaired t-test, with p-value shown at the top and the number of patients in each category shown at the bottom of each panel). ACLE, acute cutaneous lupus; DLE, discoid lupus erythematosus; IFNγ, interferon gamma; IL, interleukin; SEM, standard error of the mean.
Fig. 6.
Fig. 6.. Increased circulating IgG anti-DNA and anti-Sm/RNP antibodies in patients with serositis.
(A–D) Bar graphs show the levels of IgG anti-DNA, anti-SSA, and anti-Sm/RNP in patients with (positive) or without (negative) arthritis (A), ACLE (B), DLE (C), and serositis (D) (data are presented as the mean ± SEM; unpaired t-test, with p-value shown at the top and the number of patients in each category shown at the bottom of each panel). ACLE, acute cutaneous lupus; DLE, discoid lupus erythematosus; SEM, standard error of the mean.
Fig. 7.
Fig. 7.. Multilayer model representing the interactions among T-helper-cell cytokines, circulating autoantibodies (anti-DNA, anti-Sm/RNP, and anti-Ro/SSA), and SLE manifestations.
This multilayer model summarizes the present findings, including immune dysregulation in T cell cytokines and autoantibodies that may be connected to different clinical manifestations of SLE. At the top layer, IL-10 positively correlates with LN (red). IFNɣ (purple) positively correlates with the levels of anti-DNA and anti-SSA. IL-17 (light blue) positively correlates with the levels of anti-SSA and development of discoid and class V LN. At the middle layer, anti-DNA (light brown) positively correlates with serositis, LN, and class III or IV LN; anti-Sm/RNP (dark blue) positively correlates with serositis and LN but negatively correlates with ACLE. SLE, systemic lupus erythematosus.
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References

    1. Mason LJ, Isenberg DA, Immunopathogenesis of SLE, Baillieres Clin Rheumatol, 12 (1998) 385–403. - PubMed
    1. Hahn BH, Ebling F, Singh RR, Singh RP, Karpouzas G, La Cava A, Cellular and molecular mechanisms of regulation of autoantibody production in lupus, Ann N Y Acad Sci, 1051 (2005) 433–441. - PMC - PubMed
    1. Balow JE, Clinical presentation and monitoring of lupus nephritis, Lupus, 14 (2005) 25–30. - PubMed
    1. Lopez R, Davidson JE, Beeby MD, Egger PJ, Isenberg DA, Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort, Rheumatology (Oxford), 51 (2012) 491–498. - PubMed
    1. Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, D’Agati VD, Ferrario F, Haas M, Jennette JC, Joh K, Nast CC, Noël LH, Rijnink EC, Roberts ISD, Seshan SV, Sethi S, Fogo AB, Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices, Kidney Int, 93 (2018) 789–796. - PubMed

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