Role of IL-24 in NK cell activation and its clinical implication in systemic lupus erythematosus

Essential hypertension and systemic lupus erythematosus (SLE) are devastating conditions that disproportionately affect women. SLE has heterogeneous manifestations and treatment is limited to the use of non-specific global immunosuppression. Importantly, there is an increased prevalence of hypertension in women with SLE compared to healthy controls. Isolevuglandins (IsoLGs) are oxidation products of fatty acids that form as a result of reactive oxygen species. These molecules adduct covalently to lysine residues of proteins. Adducted proteins are then presented as autoantigens to T-cells resulting in immune cell activation. Previous studies have shown an essential role of IsoLGs in immune cell activation and the development of hypertension in animal models. We hypothesize that isoLGs are important for the development of hypertension and systemic immune activation in SLE. We first examined isoLG adduct accumulation within monocytes of human subjects with SLE compared to healthy controls. By flow cytometry, we found marked accumulation of isoLG adducts within CD14 + monocytes (34.2% ± 12.4% vs 3.81% ± 2.1% of CD14 + , N = 10-11, P <0.05). We confirmed this increase in isoLG adducts by mass spectrometry. To determine a causative role of isoLG adducts in immune activation and hypertension in SLE, we employed the B6.SLE123 and NZBWF1 mouse models of SLE. Animals were treated with the isoLG scavenger 2-hydroxybenzylamine (2-HOBA) or vehicle beginning at 7 weeks and were sacrificed at 32 weeks of age. C57BL/6 and NZW were used as controls. Importantly, treatment with 2-HOBA attenuated blood pressure in both mouse models (systolic BP 136.2 ± 5.6 mmHg for B6.SLE123 vs 120.9 ± 4.46 mmHg for B6.SLE123 +2HOBA; 164.7 ± 24.4 mmHg for NZBWF1 vs 136.9 ± 14.9 mmHg for NZBWF1 +2HOBA, N = 6-8, P < 0.05). Moreover, treatment with 2-HOBA reduced albuminuria and renal injury in the B6.SLE123 model (albumin/creatinine ratio 33.8 ± 2.0 x 10 -2 μg/mg for B6.SLE123 vs 5.5 ± 0.9 x 10 -2 μg/mg for B6.SLE123 +2HOBA, N = 7-9, P < 0.05). Finally, immune cell accumulation in primary and secondary lymphoid organs is significantly attenuated by 2-HOBA. These studies suggest a critical role of isoLG adduct accumulation in both systemic immune activation and hypertension in SLE.

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The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus

Clinical Epigenetics ◽

10.1186/s13148-015-0063-7 ◽

2015 ◽

Vol 7 (1) ◽

Cited By ~ 52

Author(s):

Shuangyan Luo ◽

Yu Liu ◽

Gongping Liang ◽

Ming Zhao ◽

Haijing Wu ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cell ◽

Lupus Erythematosus ◽

Cell Activation ◽

B Cell Activation ◽

Systemic Lupus

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Biologic therapies in systemic lupus erythematosus

10.1093/med/9780198739180.003.0007 ◽

2016 ◽

Author(s):

Maria Mouyis ◽

David Isenberg

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cell Activation ◽

Lupus Erythematosus ◽

Cell Activation ◽

Treatment Options ◽

Biologic Therapies ◽

Systemic Lupus ◽

New Treatment ◽

Anti Cd20

This chapter looks at the various biologic or target therapies that have been trialled and tested in the last two decades. The treatment of systemic lupus erythematosus (SLE) has progressed over the last few years due to an increased understanding of its pathogenesis; beginning with rituximab, one of the first biologics to be used, the chapter covers therapies up to the present day. Each subsection highlights the relevant mechanism of action which has led to new treatment options: anti-CD20 and 22, anti-B cell activating factors, anti-interferon alpha and anti-T cell activation. A summarized table is available providing a concise summary of the latest biologic therapies in treating SLE. The role of biologic therapies as monotherapy is still being defined, and with time there will be further change in the treatments available and the approach to the treatment of SLE using biologic therapies.

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Role of IL-10 in the Abnormalities of Early Cell Activation Events of Lymphocytes from Patients with Systemic Lupus Erythematosus

Journal of Autoimmunity ◽

10.1006/jaut.1998.0228 ◽

1998 ◽

Vol 11 (5) ◽

pp. 395-402 ◽

Cited By ~ 10

Author(s):

Roberto González-Amaro ◽

Diana Portales-Pérez ◽

Lourdes Baranda ◽

Carlos Abud-Mendoza ◽

Luis Llorente ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Cell Activation ◽

Systemic Lupus

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The role of microRNAs (MiR-125a and MiR-146a), RANTES, and IFN-γin systemic lupus erythematosus

10.36295/asro.2020.231382 ◽

2020 ◽

Vol 23 (13) ◽

Author(s):

Ikram khazal Qasim Al- hasso ◽

Aida Rashid Al- Derzi ◽

Ahmed Abdul-hassan Abbas ◽

Faiq I. Gorial ◽

Ahmed Sameer Alnuimi

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Systemic Lupus

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Acute interstitial nephritis and drug-induced systemic lupus erythematosus due to chlorthalidone and amiodarone: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x20910029 ◽

2020 ◽

Vol 8 ◽

pp. 2050313X2091002 ◽

Cited By ~ 1

Author(s):

Umut Selamet ◽

Ramy M Hanna ◽

Anthony Sisk ◽

Lama Abdelnour ◽

Lena Ghobry ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Interstitial Nephritis ◽

Lupus Erythematosus ◽

Kidney Biopsy ◽

Kidney Injury ◽

Acute Interstitial Nephritis ◽

Systemic Lupus ◽

Drug Induced ◽

Systemic Manifestations

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.

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Identification and stratification of systemic lupus erythematosus patients into two transcriptionally distinct clusters based on IFN-I signature

Lupus ◽

10.1177/0961203321990107 ◽

2021 ◽

pp. 096120332199010

Author(s):

Vineeta Shobha ◽

Anu Mohan ◽

AV Malini ◽

Puneet Chopra ◽

Preethi Karunanithi ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Time Course ◽

Cell Activation ◽

Immune Cell ◽

Gene Signature ◽

Systemic Lupus ◽

Auto Antibody ◽

Activation Status

Objective Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. Methods We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. Results Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. Conclusions Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.

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