Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. The disease is characterized by activation and dysregulation of both the innate and the adaptive immune systems. The autoimmune response targets self-molecules including cell nuclei, double stranded DNA and other intra and extracellular structures. Multiple susceptibility genes within the immune system have been identified, as well as disturbances in different immune pathways. SLE may affect different organs and organ systems, and organ involvement is diverse among individuals. A universal understanding of pathophysiological mechanism of the disease, as well as directed therapies, are still missing. Cytokines are immunomodulating molecules produced by cells of the immune system. Interferons (IFNs) are a broad group of cytokines, primarily produced by the innate immune system. The IFN system has been observed to be dysregulated in SLE, and therefore IFNs have been extensively studied with a hope to understand the disease mechanisms and identify novel targeted therapies. In several autoimmune diseases identification and subsequent blockade of specific cytokines has led to successful therapies, for example tumor necrosis factor-alpha (TNF-α) inhibition in rheumatoid arthritis. Authors of this review have sought corresponding developments in SLE. In the current review, we cover the actual knowledge on IFNs and other studied cytokines as biomarkers and treatment targets in SLE.

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Systemic Lupus Erythematosus Disease: An Overview of the Clinical Approach to Pathogenesis, Diagnosis, and Treatment

Borneo Journal of Pharmacy ◽

10.33084/bjop.v4i2.1950 ◽

2021 ◽

Vol 4 (2) ◽

pp. 91-98

Author(s):

Saurabh Nimesh ◽

Md. Iftekhar Ahmad ◽

Shikhka Dhama ◽

Pradeep Kumar ◽

Muhammad Akram ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Chronic Disease ◽

Lupus Erythematosus ◽

The Body ◽

Clinical Approach ◽

Systemic Lupus Erythematosus Disease ◽

Systemic Lupus ◽

Organ Systems ◽

Novel Approaches

The systemic lupus erythematosus (SLE), commonly known as Lupus, is a rare and complex multisystem autoimmune disease where one’s immune system is overactive, and the body attacks its organ systems. SLE is a historically old disease described already in antiquity; it is an example of a chronic disease with physical, psychological, financial, and social implications for individuals diagnosed. It has inspired medical and basic biological scientists that focus on molecular biology, basic immunology, immunopathology, clinical science, genetics, and epidemiology. The syndrome is real in its existence-although hidden behind obstacles, cumbersome for patients and clinicians, and rebellious for scientists. There is currently no cure for SLE. The goal of treatment is to ease symptoms. This article will review information on the general approach to SLE therapy, focusing on currently approved therapies and novel approaches that might be used in the future.

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Autoimmune Polyglandular Syndrome Type 3-D

10.21467/preprints.367 ◽

2022 ◽

Author(s):

Fadel Fikri Suharto ◽

RM Dewi Anggraini ◽

Ardianto Tamin ◽

Della Fitricana ◽

Nova Kurniati ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Autoimmune Disease ◽

Lupus Erythematosus ◽

Disease Patient ◽

The Body ◽

Graves Disease ◽

Systemic Lupus ◽

Metabolic System ◽

Organ Systems

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by the presence of autoantibodies against cell nuclei and involves many organ systems in the body. The etiopathology of SLE is thought to involve complex and multifactorial interactions between genetic variation and environmental factors. Hyperthyroidism is a disease due to increased thyroid hormone function followed by signs and symptoms that affect the body's metabolic system. Graves' disease is an autoimmune disease characterized by the presence of antibodies to TSHR (TRAb). Several coexisting autoimmune diseases have been classified under different syndromes. Case Presentation: A woman, 29 years-old, came to office with complaint of chest palpitation. Patient had history of fever, joint pain, hair loss, and malar rash. Patient had been diagnosed with hyperthyroidism for 4 years and regularly taking propylthiouracil 100 mg and propranolol 10 mg. Titer ANA Test 1/100, Anti ds-DNA 68.08, C3-Complement 93 (N: 83-193), C4-Complement 11.2 (N: 15-57), Free T3 7.79 (N: 1.71-3.71), Free -T4 2.50 (N: 0.70-1.48), TSHs 0.0001 (N: 0.350-4.94), TRAb 3.38 (N: < 1.75). Patient was diagnosed with systemic lupus erythematosus (SLE) and graves’ disease. Patient treated with methimazole 10 mg, propranolol 10 mg, myfortic 360 mg, and methylprednisolone 4 mg. Conclusion: Autoimmune Polyendocrine Syndromes (APS) was at first characterized as different endocrine organ diseases related to an immune system disease in a subject. Hence, affiliation between illnesses in APS was noted not to be irregular but in specific combinations in which a few non-endocrine immune system diseases were moreover portion of the disorders.

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Polyglandular Autoimmune Syndrome Type 3D : A Case Report

10.31219/osf.io/ry7dc ◽

2022 ◽

Author(s):

Fadel Fikri

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Autoimmune Disease ◽

Lupus Erythematosus ◽

Disease Patient ◽

The Body ◽

Systemic Lupus ◽

Metabolic System ◽

Polyglandular Autoimmune Syndrome ◽

Organ Systems

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by the presence of autoantibodies against cell nuclei and involves many organ systems in the body. The etiopathology of SLE is thought to involve complex and multifactorial interactions between genetic variation and environmental factors. Hyperthyroidism is a disease due to increased thyroid hormone function followed by signs and symptoms that affect the body's metabolic system. Graves' disease is an autoimmune disease characterized by the presence of antibodies to TSHR (TRAb). Several coexisting autoimmune diseases have been classified under different syndromes. Autoimmune Polyglandular Syndrome (PGAS),Case Presentation: A woman, 29 years-old, came to office with complaint of chest palpitation. Patient had history of fever, joint pain, hair loss, and malar rash. Patient had been diagnosed with hyperthyroidism for 4 years and regularly taking propylthiouracil 100 mg and propranolol 10 mg. Titer ANA Test 1/100, Anti ds-DNA 68.08, C3-Complement 93 (N: 83-193), C4-Complement 11.2 (N: 15-57), Free T3 7.79 (N: 1.71-3.71), Free -T4 2.50 (N: 0.70-1.48), TSHs 0.0001 (N: 0.350-4.94), TRAb 3.38 (N: < 1.75). Patient was diagnosed with systemic lupus erythematosus (SLE) and grave's disease. Patient treated with methimazole 10 mg, propranolol 10 mg, myfortic 360 mg, and methylprednisolone 4 mg.Conclusion: Autoimmune Polyendocrine Syndromes (APS) was at first characterized as different endocrine organ diseases related to an immune system disease in a subject. Hence, affiliation between illnesses in APS was noted not to be irregular but in specific combinations in which a few non-endocrine immune system diseases were moreover portion of the disorders.

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LUPUS

The Professional Medical Journal ◽

10.29309/tpmj/2008.15.01.2717 ◽

2008 ◽

Vol 15 (01) ◽

pp. 179-184

Author(s):

NAGEEN HUSSAIN

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Lupus Erythematosus ◽

Immune Complexes ◽

Autoimmune Disorder ◽

Multiple Organ ◽

The Self ◽

Systemic Lupus ◽

Organ Systems ◽

Self Antigens

Lupus is an autoimmune disorder in which the immune system becomeshyperactive; results in the formation of auto-antibodies that react with the “self” antigens to form immune complexes.These immune complexes build up in the tissues; can cause inflammation, injury to tissues, pain and bring about thesymptoms . Systemic Lupus Erythematosus (SLE) is one of the type of lupus which affects multiple organ systems 1,2and is multifactorial in etiology .2,3

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THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.2.9 ◽

2018 ◽

pp. 52-58

Author(s):

Le Thuan Nguyen ◽

Bui Bao Hoang

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Activity Index ◽

Clinical Manifestations ◽

Systemic Lupus ◽

Cross Sectional ◽

Organ Systems ◽

Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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Living with systemic lupus erythematosus in 2020: a European patient survey

Lupus Science & Medicine ◽

10.1136/lupus-2020-000469 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000469

Author(s):

Alain Cornet ◽

Jeanette Andersen ◽

Kirsi Myllys ◽

Angela Edwards ◽

Laurent Arnaud

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Online Survey ◽

Complex Disease ◽

Renal Involvement ◽

Median Number ◽

Sexual Life ◽

Diagnosis Delay ◽

Systemic Lupus ◽

Organ Systems

ObjectiveThe aim of this study was to analyse the 2020 burden of Systemic Lupus Erythematosus (SLE) in Europe, from the patients’ perspective.MethodsIn May 2020, Lupus Europe, the European umbrella patient association for SLE, designed and disseminated a multilingual anonymous online survey to individuals with a self-reported physician’s diagnosis of SLE living in Europe.ResultsData from 4375 SLE survey respondents (95.9% women, median age: 45 (IQR: 36–54) years, 70.7% Caucasians) from 35 European countries were analysed. The median age at SLE diagnosis was 30 years (IQR: 22–40) and the median diagnosis delay was 2 years (IQR: 0–6). The most commonly affected organ-systems included the joints (81.8%) and skin (59.4%), with renal involvement in 30%. Another diagnosis was given before that of SLE in 45.0%, including psychological/mental disorders in 9.1% and fibromyalgia in 5.9%. The median number of symptoms reported was 9 (IQR: 6–11) out of 21, with fatigue most common (85.3%) and most bothersome. The median number of SLE-related medications was 5 (IQR: 3–7), including antimalarials (75%), oral glucocorticoids (52.4%), immunosuppressants (39.8%) and biologics (10.9%). Respondents reported significant impact over their studies, career and emotional/sexual life in 50.7%, 57.9% and 38.2%, respectively. Appropriate access to care was highly variable across countries and care component.ConclusionThis survey underlines the 2020 burden and strong heterogeneity in the care of SLE across Europe, from the patient’s perspective. Altogether, these data may prove crucial to physicians, patients and policy-makers to improve the diagnosis and management of this rare and complex disease.

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Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, Thrombotic Microangiopathy and ANCA-Vasculitis

International Journal of Molecular Sciences ◽

10.3390/ijms22084194 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4194

Author(s):

Martina Mazzariol ◽

Giovanni Camussi ◽

Maria Felice Brizzi

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Autoimmune Diseases ◽

Extracellular Vesicles ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Thrombotic Microangiopathy ◽

Coagulation Cascade ◽

Renal Diseases ◽

Systemic Lupus

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.

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Anti-Carbamylated Protein Antibodies, Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus

Reumatología Clínica ◽

10.1016/j.reuma.2021.05.006 ◽

2021 ◽

Author(s):

Mohamed Sherif El Hawary ◽

Sarah A. Hassan ◽

Sahar Abd ELatty ◽

Noha M. Khalil

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Tumour Necrosis ◽

Tumour Necrosis Factor Alpha ◽

Systemic Lupus ◽

Necrosis Factor Alpha ◽

Egyptian Patients ◽

Factor Alpha ◽

Necrosis Factor

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Increased Frequency of the Uncommon Allele of a Tumour Necrosis Factor Alpha Gene Polymorphism in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Disease Markers ◽

10.1155/1994/756247 ◽

1994 ◽

Vol 12 (2) ◽

pp. 127-133 ◽

Cited By ~ 88

Author(s):

Victor A. Danis ◽

Michelle Millington ◽

Valentine Hyland ◽

Ron Lawford ◽

Qirong Huang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Tumour Necrosis Factor ◽

Lupus Erythematosus ◽

Tumour Necrosis ◽

Tumour Necrosis Factor Alpha ◽

Systemic Lupus ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

The frequency of the uncommon allele (TNF2) of a polymorphism in the promoter region of the tumour necrosis factor alpha (TN Fα) gene in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was found to be 3 times that of the normal anglo-saxon population. In SLE patients, this allele was strongly associated with HLA-DR3 expression and was also more frequent in patients who did not have malar rash. Functional studies of normal monocyte cytokine production in vitro showed that this genotype was associated with increased IL-1α protein production but there were no differences in the production of TNFα protein.

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