DNA damages in peripheral white blood cells with systemic lupus erythematosus

Author(s):  
N.A. Iljushina ◽  
T.M. Reshetnjak ◽  
E.Yu. Moskaleva
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


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.


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 22 (5) ◽  
pp. 987-992
Author(s):  
V. V. Zhelezko ◽  
I. A. Novikova

The article presents the data on assessment of functional features of neutrophils in 34 patients with systemic lupus erythematosus (SLE). Development of neutrophil extracellular traps (NETs) was evaluated in cell cultures incubated in vitro for 30 and 150 minutes (basal levels, NETBAS30 and NETBAS150, respectively), and in the presence of heat-inactivated S. аureus (strain ATCC 25923, 108 CFU/ml) (stimulated levels, NETST30 and NETST150, respectively). NET looks like thin free-lying extracellular fibrillar structures, 2-3 times exceeding the size of unchanged granulocyte. The result was expressed as percentage and relative amount of extracellular traps per 100 counted leukocytes. Phagocytic activity of neutrophils was evaluated as phagocytosis of S. аureus by counting the percentage of neutrophils that engulfed phagocytic index of microbial particles (PI); the average number of phagocytosed objects per neutrophil phagocytic number (PC). ROS-producing activity was determined in the reduction of Nitroblue Tetrazolium tested in spontaneous and stimulated S. аureus variants (NBTBAS and NBTST, respectively). The result was expressed as the percentage of formazan-positive cells per 100 white blood cells. Nitroxide-producing properties were determined using the Crow (1999) method in spontaneous and stimulated samples for the accumulation of the nitrated amino acid tyrosine (3-nitrothyrosine, 3-NTBAS, and 3-NTST, respectively). We revealed a decrease in ROS production, phagocytosis and NO-forming activity of neutrophils associated with increased netosis. Activation of the netosis was observed in cell cultures without stimulation, indicating the in vivo formation of networks in SLE. The NET increase is most pronounced in the patients with lupus nephritis (p < 0.05), and in remission of the disease (p < 0.05). We have revealed a correlation of NET formation parameters with duration and degree of SLE activity (rs = -0.6; p = 0.001, and rs = 0.39; p = 0.02, respectively); autoantibody titers (anti-dsDNA and ANA) (rs = 0.67; р = 0.047 and rs = 0.59; р = 0.034, respectively); prothrombin complex activity (rs = 0.6; p = 0.036), as well and urea and creatinine levels (rs = 0.47; p = 0.037 and rs = 0.39; p = 0.048, respectively). The parameters of NETs can be considered a promising biomarker for verifying the diagnosis of SLE, evaluation of clinical activity, disease severity, and predicting the development of complications.


2021 ◽  
pp. 120-121
Author(s):  
Floranne C. Ernste

A 33-year-old woman with systemic lupus erythematosus, diagnosed 2 years prior and treated with hydroxychloroquine, sought care for a 4-week history of pain and paresthesias in her low back and lower extremities. She described a bandlike sensation of numbness starting in her midback which descended to both legs. Her symptoms progressed to constipation and inability to urinate adequately. She reported difficulty with ambulation. Over the course of 1 week of hospitalization, urinary and fecal incontinence developed. On examination, she was alert and appropriately oriented. She had a malar rash and swelling of the metacarpophalangeal joints consistent with bilateral hand synovitis. Neurologic examination indicated hyperreflexia with brisk patellar and Achilles tendon reflexes bilaterally. She had trace motor weakness of the hip flexors, quadriceps, and hamstrings. She had loss of pinprick and temperature sensation in the lower extremities, extending beyond the saddle area to the T12 dermatome. Vibration perception and proprioception were preserved. She had a positive Babinski sign in the left foot. Her cerebellar examination showed slowing of rapid alternating movements in the left hand. Magnetic resonance imaging of the lumbosacral spine indicated subtle T2 signal change of the intramedullary conus and enhancement of the cauda equina nerve roots. Cerebrospinal fluid analysis showed an increased protein concentration. Two white blood cells/µL were found in the cerebrospinal fluid. The serum antinuclear antibody was strongly positive, and the anti–double-stranded DNA antibody level was greater than 1,000 IU/mL. The serum complement levels were low. Lupus anticoagulant, beta-2 glycoprotein antibodies, and antiphospholipid antibodies were increased, at greater than twice the upper limits of normal. Electromyography indicated multiple sacral radiculopathies. The patient was diagnosed with autoimmune myeloradiculitis as a neuropsychiatric manifestation of systemic lupus erythematosus (neuropsychiatric systemic lupus erythematosus). The patient received methylprednisolone followed by prednisone, with a gradual taper. Her hospital course was complicated by the development of deep venous thromboses in the bilateral lower extremities. She was started on heparin and transitioned to warfarin therapy. She started mycophenolate mofetil. Hydroxychloroquine was continued. At a 24-month follow-up visit, the patient remained in neurologic remission. Neuropsychiatric systemic lupus erythematosus events consist of a heterogeneous array of neurologic and psychiatric disorders including intractable headaches, cognitive dysfunction, psychosis, seizure disorders, transverse myelitis, aseptic meningitis, cranial neuropathies, and acute inflammatory demyelinating polyneuropathy.


Sign in / Sign up

Export Citation Format

Share Document