scholarly journals IL-12 and IL-23/Th17 axis in systemic lupus erythematosus

2019 ◽  
Vol 244 (1) ◽  
pp. 42-51 ◽  
Author(s):  
Maddalena Larosa ◽  
Margherita Zen ◽  
Mariele Gatto ◽  
Diogo Jesus ◽  
Elisabetta Zanatta ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Monoclonal Antibody ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Therapeutic Strategy ◽  
Complex Disease ◽  
Controlled Trial ◽  
Special Focus ◽  
Systemic Lupus ◽  
Novel Therapeutic

Systemic lupus erythematosus (SLE) is a very complex disease where multiple immunological pathways can concur in inducing tissue damage. Cytokines are key mediators in this process and among them the role of interleukin (IL)-12 and the IL-23/Th17 axis has recently emerged. IL-12 and IL-23 have a heterodimeric structure with a common subunit, named p40. Although they share a partially common structure, their functions appear slightly different. Indeed, IL-12 is a key cytokine in inducing an efficient T helper 1 (Th1) response and in Th differentiation, while IL-23 plays a crucial role in chronic inflammation and Th17 cell activation, which results in IL-17 secretion. The increasing knowledge on the interaction between IL-12 and IL-23/Th17 axis in the development of autoimmune diseases has led to the identification of new therapeutic strategies targeting these immunological pathways. IL-23/Th17 axis has recently been suggested to be essential in developing lupus nephritis, both in mice and in humans. In keeping with these observations, ustekinumab, a fully human IgG1κ monoclonal antibody (mAb) directed towards p40 subunit, has been investigated in SLE. Promising data from a phase II randomized controlled trial in SLE patients suggest that this mAb might be a potential novel therapeutic strategy in SLE. In this review, we summarize the complex interaction between IL-12 and IL-23/Th17 axis in SLE with a special focus on drugs which affect this immune pathway. Impact statement Our article is focused on emerging pathogenetic pathways in systemic lupus erythematosus (SLE). Notably, IL-12 and IL-23 have been described as emerging cytokines in SLE pathogenesis. We know that IL-23 stimulates Th17 cells to produce IL-17. We try to point out the importance of IL-23/Th17 axis in SLE and to focus on the interaction between this axis and IL-12. Ustekinumab, a fully human IgG1κ monoclonal antibody directed towards the p40 shared subunit of IL-12 and IL-23, has been recently investigated in SLE, suggesting a potential novel therapeutic strategy in SLE. To our knowledge, there are no reviews which simultaneously focus on IL-12 an IL-23/Th17 axis in SLE. Thus, we believe our work will be of interest to the readers.

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

Lupus ◽  
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.

Immunoglobulin levels in systemic lupus erythematosus: A narrative review

Lupus ◽  
2021 ◽  
pp. 096120332110047
Author(s):  
Ibrahim Almaghlouth ◽  
Sindhu R Johnson ◽  
Eleanor Pullenayegum ◽  
Dafna Gladman ◽  
Murray Urowitz
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Narrative Review ◽  
Special Focus ◽  
Immunoglobulin Level ◽  
Systemic Lupus ◽  
External Threats ◽  
Self Tolerance ◽  
Low Levels ◽  
The Impact

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

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

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.

Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial

2009 ◽  
Vol 69 (6) ◽  
pp. 1144-1147 ◽  
Author(s):  
A Hartkamp ◽  
R Geenen ◽  
G L R Godaert ◽  
M Bijl ◽  
J W J Bijlsma ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Controlled Trial ◽  
Well Being ◽  
Controlled Study ◽  
Systemic Lupus ◽  
Double Blind ◽  
Female Patients ◽  
General Fatigue ◽  
Mental Well Being

ObjectiveDehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE.MethodsIn a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment.ResultsPatients from the DHEA and placebo group improved on general fatigue (p<0.001) and mental well-being (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p=0.04).ConclusionsThe trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE.Clinical Trials Registration Number NCT00391924

Controlled trial with chloroquine diphosphate in systemic lupus erythematosus

Lupus ◽  
1996 ◽  
Vol 5 (3) ◽  
pp. 237-241 ◽  
Author(s):  
IM Meinão ◽  
EI Sato ◽  
Lec Andrade ◽  
MB Ferraz ◽  
E. Atra
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Controlled Trial ◽  
Systemic Lupus ◽  
Chloroquine Diphosphate
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