scholarly journals Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood

2003 ◽  
Vol 197 (6) ◽  
pp. 711-723 ◽  
Author(s):  
Lynda Bennett ◽  
A. Karolina Palucka ◽  
Edsel Arce ◽  
Victoria Cantrell ◽  
Josef Borvak ◽  
...  

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity. Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes. A more liberal correction (Benjamini and Hochberg correction) yielded 18 additional genes, 12 of which are IFN-regulated and 4 granulocyte-specific. Indeed immature neutrophils were identified in a large fraction of SLE patients white blood cells. High dose glucocorticoids, a standard treatment of disease flares, shuts down the interferon signature, further supporting the role of this cytokine in SLE. The expression of 10 genes correlated with disease activity according to the SLEDAI. The most striking correlation (P < 0.001, r = 0.55) was found with the formyl peptide receptor-like 1 protein that mediates chemotactic activities of defensins. Therefore, while the IFN signature confirms the central role of this cytokine in SLE, microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis.

2015 ◽  
Vol 42 (3) ◽  
pp. 437-440 ◽  
Author(s):  
Jonathan Y.C. Ding ◽  
Dominique Ibañez ◽  
Dafna D. Gladman ◽  
Murray B. Urowitz

Objective.To identify patients presenting with isolated hematuria and/or pyuria in the absence of other systemic lupus erythematosus (SLE) disease activity, describe their demographics, and determine whether they present with evidence of SLE flare in a period adjacent to the presentation.Methods.We studied patients followed at the University of Toronto Lupus Clinic between 1970 and 2012. An episode of isolated hematuria (> 5 red blood cells per high power field) and/or pyuria (> 5 white blood cells per high power field) was defined as 2 consecutive visits with these findings in the absence of other concurrent SLE manifestations such as proteinuria, casts, or azotemia. We then excluded patients whose findings might be explained by urinary tract infections, menstruation, urolithiasis, and/or anticoagulation. Only patients presenting with no other SLE disease activity were included.Results.Isolated hematuria and/or pyuria were identified in 49 patients, of whom 17 were excluded according to the criteria above, leaving 32. Twenty-four patients had another renal manifestation 1 year before and/or after the occurrence; 27 had a non-renal manifestation 1 year before and/or after the occurrence; 3 patients had a biopsy in the same time frame, all with evidence of active lupus nephritis. Therefore the majority of patients with an occurrence of isolated hematuria and/or pyuria had evidence of renal or other non-renal SLE disease activity at a time adjacent to this presentation.Conclusion.Although not proven, our results suggest that these manifestations were associated with SLE activity, either before or after the episode, and therefore may represent a phase of active disease.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 634.1-634
Author(s):  
T. Fu ◽  
Y. Yang ◽  
X. Gu ◽  
C. Dong ◽  
R. Zhao ◽  
...  

Background:SLE is an autoimmune disease characterized by the abnormal function of lymphocytes. The impairment of hematopoietic function of bone marrow participates in its pathogenesis, in which T cells play an important role. However, study on bone marrow T cells in SLE patients is very limited.Objectives:This study aims to characterize the phenotype and molecular characteristics of abnormally activated CD8+T cells in bone marrow of SLE patients and explore the mechanism of hematopoietic stem cells (HSCs) reduction caused by the abnormally activated CD8+T cells in bone marrow of patients with SLE.Methods:A total of 8 SLE patients and 5 age- and sex-matched controls were recruited in our study. Among them, 3 SLE patients and 4 donors were collected bone marrow and peripheral blood samples for Single-cell RNA sequencing (scRNA-seq) and functional studies. BM and peripheral T cell subsets were measured by flow cytometry. Plasma cytokines and secreted immunoglobulins were detected by Luminex. Disease activity of SLE patients was measured using the SLE Disease Activity Index (SLEDAI). All analyses were performed using R language and Flowjo 9.Results:In the present study, SLE patients had increased CD8+T%αβT cells and decreased CD4+T%αβT cells in bone marrow of SLE, compared to healthy controls. A large number of CD38+HLADR+CD8+T cells existed in the bone marrow and peripheral blood of SLE patients. Those patients also showed reduced number of HSCs, and with a downward trend of the numbers of peripheral red blood cells, white blood cells, neutrophils, hemoglobin, and platelets. By scRNA-seq, the CD38+HLADR+CD8+T cells contained high levels of GZMK, GZMA, PRF1, IFNG, and TNF in the bone marrow of SLE patients. the CD38+HLADR+CD8+T cells exhibited significant relationship with HSCs, white blood cells, neutrophils, and platelets.Conclusion:These findings demonstrated that the abnormally activated CD8+T cells in bone marrow can reduce the number of HSCs by the expression of killer molecules, which contributes to the impairment of hematopoietic function and the development of SLE. This project focuses on the specific bone marrow T cell subset in SLE. The completement of this project provides information for exploring the mechanism of hematopoiesis involvement.References:[1]Anderson E, Shah B, Davidson A, Furie R. Lessons learned from bone marrow failure in systemic lupus erythematosus: Case reports and review of the literature. Semin Arthritis Rheum. 2018;48(1):90-104.[2]Sun LY, Zhou KX, Feng XB, Zhang HY, Ding XQ, Jin O, Lu LW, Lau CS, Hou YY, Fan LM. Abnormal surface markers expression on bone marrow CD34+cells and correlation with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol. 2007;26(12):2073-2079.Acknowledgements:We want to thank Lu Meng, Teng Li, Wei Zhou, and Jiaxin Guo for their assistance with this study.Disclosure of Interests:None declared


Blood ◽  
1954 ◽  
Vol 9 (12) ◽  
pp. 1165-1171 ◽  
Author(s):  
ANA E. CARRERA ◽  
MAY VIRGINIA REID ◽  
N. B. KURNICK

Abstract Recent investigations have demonstrated that the lupus erythematosus cell phenomenon is influenced, among other things, by intracellular factors. The hypothesis was formulated that leucocytes from different animal species would react with different degrees of intensity to the same L. E. serum. Leucocytes from twelve animal species were tested by counting the number of L. E. cells, "globs" (free homogeneous basophilic masses), droplets and rosettes per 1000 white blood cells and per 1000 P.M.N. after 2 hours’ incubation in the L. E. serum. Controls consisted of similar preparations using normal human serum and homologous plasma. There was a wide range of susceptibility among the various species tested. The chicken and the horse were the most susceptible species, while man fell low in the scale of susceptibility. Classical L. E. cells were produced from leucocytes of most species tested. It is felt that a highly sensitive L. E. test can be performed, using chicken, horse, guinea pig, or dog, instead of human leucocytes.


2020 ◽  
Vol 36 (6) ◽  
Author(s):  
Lai-Run Jin ◽  
Meng-Jun Tao ◽  
Jun Zhou ◽  
Liang Xu ◽  
Qiang Li ◽  
...  

Background and Objective: Prevention and control of metabolic syndrome is the key to improving the development of systemic lupus erythematosus. The aim of this study was to analyze the relevant factors regarding metabolic syndrome (MS) in systemic lupus erythematosus (SLE). Methods: A total number of 1238 SLE patients in Yijishan Hospital of Wannan Medical College, Anhui province, from February 2012 to July 2017, were analyzed retrospectively. SLE patients with MS were grouped to group SLE-MS, the others without MS was grouped to group SLE-nMS. The two groups were compared with respect to general characteristics, clinical signs, and laboratory parameters. Random forest approach and multivariate logistic regression were conducted to analyze the related factors regarding MS in SLE. Results: The constituent ratio of metabolic syndrome was 27.14% (336/1238). More SLE patients with MS presented with more farmers, more married people, lower education level, and more lupus nephritis, proteinuria, oral ulcers, tubular urine, hematuria than SLE patients without MS (P<0.05). Moreover, eighteen important variables, whose average importance scores were highest and whose error rates were lowest, were selected by random forest method. Data from multivariate logistic regression showed that MS in SLE was related with BMI, diastolic blood pressure, systolic blood pressure, fasting blood glucose, arthritis, urea, triglycerides, high-density lipoprotein, and white blood cells. Conclusion: MS in SLE was closely related to BMI, blood pressure, blood sugar, blood lipids, arthritis, white blood cells, and urea. Targeted prevention and conclusion measures for the risk factors should be taken as early as possible. doi: https://doi.org/10.12669/pjms.36.6.2093 How to cite this:Jin LR, Tao MJ, Zhou J, Xu L, Li Q, Li Z, et al. Metabolic syndrome in systemic lupus erythematosus was closely related to body mass index, blood pressure, blood sugar, blood lipids, and arthritis. Pak J Med Sci. 2020;36(6):---------.  doi: https://doi.org/10.12669/pjms.36.6.2093 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091002 ◽  
Author(s):  
Umut Selamet ◽  
Ramy M Hanna ◽  
Anthony Sisk ◽  
Lama Abdelnour ◽  
Lena Ghobry ◽  
...  

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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