scholarly journals Acropulpitis in systemic lupus erythematosus is associated with high type 1 interferon signature

2021 ◽  
Author(s):  
Gabrielle Sonigo ◽  
Charles Cassius ◽  
Maxime Battistella ◽  
Hélène Le Buanec ◽  
Martine Bagot ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
High Type ◽  
Interferon Signature ◽  
Type 1 Interferon

scholarly journals The peptide symporter SLC15a4 is essential for the development of systemic lupus erythematosus in murine models

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244439
Author(s):  
Arna Katewa ◽  
Eric Suto ◽  
Jessica Hui ◽  
Jose Heredia ◽  
Jie Liang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Response ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Pharmacological Intervention ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Type 1 Interferon ◽  
Cell Functions

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease representing a serious unmet medical need. The disease is associated with the loss of self-tolerance and exaggerated B cell activation, resulting in autoantibody production and the formation of immune complexes that accumulate in the kidney, causing glomerulonephritis. TLR7, an important mediator of the innate immune response, drives the expression of type-1 interferon (IFN), which leads to expression of type-1 IFN induced genes and aggravates lupus pathology. Because the lysosomal peptide symporter slc15a4 is critically required for type-1 interferon production by pDC, and for certain B cell functions in response to TLR7 and TLR9 signals, we considered it as a potential target for pharmacological intervention in SLE. We deleted the slc15a4 gene in C57BL/6, NZB, and NZW mice and found that pristane-challenged slc15a4-/- mice in the C57BL/6 background and lupus prone slc15a4-/- NZB/W F1 mice were both completely protected from lupus like disease. In the NZB/W F1 model, protection persisted even when disease development was accelerated with an adenovirus encoding IFNα, emphasizing a broad role of slc15a4 in disease initiation. Our results establish a non-redundant function of slc15a4 in regulating both innate and adaptive components of the immune response in SLE pathobiology and suggest that it may be an attractive drug target.

A single nucleotide polymorphism in theNCF1gene leading to reduced oxidative burst is associated with systemic lupus erythematosus

2017 ◽  
Vol 76 (9) ◽  
pp. 1607-1613 ◽  
Author(s):  
Lina M Olsson ◽  
Åsa C Johansson ◽  
Birgitta Gullstrand ◽  
Andreas Jönsen ◽  
Saedis Saevarsdottir ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Single Nucleotide Polymorphism ◽  
Lupus Erythematosus ◽  
Ros Production ◽  
Nucleotide Polymorphism ◽  
Systemic Lupus ◽  
Isolated Cells ◽  
Single Nucleotide ◽  
Type 1 Interferon

ObjectivesNcf1polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases in animal models. The humanNCF1gene is very complex with both functional and non-functional gene copies and genotyping requires assays specific for functionalNCF1genes. We aimed at investigating association and function of the missense single nucleotide polymorphism (SNP), rs201802880 (here denoted NCF1-339) inNCF1with systemic lupus erythematosus (SLE).MethodsWe genotyped the NCF1-339 SNP in 973 Swedish patients with SLE and 1301 controls, using nested PCR and pyrosequencing. ROS production and gene expression of type 1 interferon-regulated genes were measured in isolated cells from subjects with different NCF1-339 genotypes.ResultsWe found an increased frequency of the NCF1-339 T allele in patients with SLE, 11% compared with 4% in controls, OR 3.0, 95% CI 2.4 to 3.9, p=7.0×10−20. The NCF1-339 T allele reduced extracellular ROS production in neutrophils (p=0.004) and led to an increase expression of type 1 interferon-regulated genes. In addition, the NCF1-339 T allele was associated with a younger age at diagnosis of SLE; mean age 30.3 compared with 35.9, p=2.0×1−6.ConclusionsThese results clearly demonstrate that a genetically controlled reduced production of ROS increases the risk of developing SLE and confirm the hypothesis that ROS regulate chronic autoimmune inflammatory diseases.

Autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus in pediatric systemic lupus erythematosus: Results from the CARRA Legacy Registry

Lupus ◽  
2020 ◽  
Vol 29 (14) ◽  
pp. 1926-1936
Author(s):  
Ohoud AlAhmed ◽  
Vidya Sivaraman ◽  
Melissa Moore-Clingenpeel ◽  
Stacy P Ardoin ◽  
Sharon Bout-Tabaku ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Pediatric Systemic Lupus Erythematosus ◽  
Over Time ◽  
Lupus Disease Activity

Objective Polyautoimmunity (PA) with systemic lupus erythematosus (SLE) is reported as a poor prognostic factor, but little is known about its effect in childhood-onset SLE (cSLE). We describe PA in cSLE within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry and evaluate its association to lupus disease outcomes. Methods CARRA Legacy Registry is the largest pediatric rheumatology registry that collected data at enrollment and every 6 months thereafter. We describe the co-occurrence of selected autoimmune disorders (autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus) in cSLE. To assess outcomes, we studied measures of lupus disease activity, complications, and patient’s quality of life (QoL). Comparisons by PA status were made using chi-square, Fisher’s exact test, two-sample t-tests, Wilcoxon rank sum tests, and mixed effects models as appropriate. Results 1285 patients met the American College of Rheumatology criteria for SLE. Of those, 388 (30%) had data on comorbidity. The prevalence of PA was 8.8%. Patients with PA reported more hospitalizations and aggressive immunotherapy use. SLEDAI and PGA scores improved over time, but did not differ by PA status. No significant differences were found in QoL measures or their trajectory over time by PA status. Conclusion In cSLE, PA is associated with more hospitalizations and aggressive immunotherapy use. Although lupus disease activity improved over time, patients' QoL neither improved over time nor differed by having other autoimmune disease. Prospective, case-control, long-term follow-up studies on cSLE are needed to validate our results. MeSH Key Indexing Terms Pediatric systemic lupus erythematosus; Autoimmune diseases; Outcome assessment

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