Cytokines in Systemic lupus erythematosus.

Lupus Erythematosus ◽

Pearson Correlation ◽

Caribbean Region ◽

Type I ◽

Healthy Controls ◽

Childbearing Age ◽

Systemic Lupus ◽

Sledai Score ◽

The systemic lupus erythematosus (SLE) is the greatest manifestation of autoimmunity. It is characterized by the presence of cytokines, including type I and II interferons, interleukin-6 (IL-6), IL-1, and tumor necrosis factor-alpha (TNF-α), the immunomodulatory cytokines like IL-10 and TGF-β, be essential players in SLE. Additionally, T-cell-derived cytokines like IL-17A, IL-21, and IL-2 are dysregulated in SLE. In this paper, a prospective cross-sectional and observational study was done. It was measured the levels of 3 essential cytokines in SLE: IL-17A, IL-23, and IL-33 using three enzyme-linked immunosorbent assays (ELISA). Thirty (30) patients attending the rheumatoid clinic at one of the major regional hospitals in the Caribbean region were recruited. Mostly females above the childbearing age give their consent to be included in the study and other 30 healthy patients were used a control. Of all the SLE patients, 15 (50%) patients were of Afro-Caribbean descent, 12 (40%) of patients were of Indo-Caribbean descent, and 3 (10%) of patients were of mixed descent. Nineteen (63%) healthy controls were females, and 11 (37%) were males. The results showed that serum IL-17A and IL-23 were more significantly higher in SLE patients than controls (P<0.01); however, there was no statistically significant difference between IL-33 levels between SLE patients and healthy controls. The study showed no correlation between serum IL-17A and IL-23 in SLE patients as judged by the result of the Pearson correlation coefficient (r=0.308, p>0.05). It also showed that serum IL-17A and IL-23 levels positively correlate to the SLE disease activity index 2000 score (SLEDAI score). Nevertheless, IL-33 levels show no correlation with the SLEDAI score. In this study, higher cytokines were reported mostly in patients between the ages of 25 to 30-year-old and Afro-Caribbean descent.

Competence of medical and obstetric registrars in the management of systemic lupus erythematosus in pregnancy

Obstetric Medicine ◽

10.1177/1753495x20964670 ◽

2020 ◽

pp. 1753495X2096467

Author(s):

Jarrod Zamparini ◽

Stuart Pattinson ◽

Kavita Makan

Keyword(s):

South Africa ◽

Pregnant Women ◽

Lupus Erythematosus ◽

Pass Rate ◽

Childbearing Age ◽

Systemic Lupus ◽

Significant Difference ◽

General Physicians ◽

In Pregnancy

Introduction Systemic lupus erythematosus has a predilection for women of childbearing age. Globally a shortage of rheumatologists exists resulting in general physicians and obstetricians treating systemic lupus erythematosus in pregnancy. Methods We conducted a survey amongst medical and obstetric registrars in South Africa to assess their subjective and objective competence in managing pregnant women with systemic lupus erythematosus. Results The pass rate for the objective section was 70.8% with no statistically significant difference in the pass rate between medical and obstetric registrars. Participants felt unprepared to manage pregnant women with systemic lupus erythematosus, with a mean overall score of 3.4 out of 7 for the subjective section, based on four Likert scale type questions. Conclusion Trainees are not able to accurately assess their own levels of competence in order to identify their learning needs. Due to the shortage of rheumatologists and lack of obstetric physicians in South Africa, general physicians and obstetricians must be equipped to provide adequate care to pregnant women with systemic lupus erythematosus.

The Auto-Antibodies on Bone Marrow Cells in the Patients with Systemic Lupus Erythematosus.

Blood ◽

10.1182/blood.v108.11.3856.3856 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3856-3856

Author(s):

Rong Fu ◽

Jizi Deng ◽

Shang Yuan ◽

Lu Gong ◽

Jun Sun ◽

...

Keyword(s):

Bone Marrow ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Healthy Controls ◽

Coombs Test ◽

Systemic Lupus ◽

Cell Counts ◽

Significant Difference ◽

Positive Rate

Abstract Objective:To explore the pathogenesis of cytopenia in the patients with systemic lupus erythematosus (SLE), the auto-antibodies on bone marrow mononuclear cells (BMMBC) in the patients with SLE were determined. Methods:Twenty one patients with SLE and ten healthy controls were enrolled in this study. BMMNC Coombs test was used to determine the aotoantibodies. The correlation between the types of auto-antibodies on BMMNC, the types of serum auto-antibodies and the counts of blood cells in the patients with SLE were also investigated. Results:Positive results of BMMBC-Coombs test were seen in 12 patients with SLE (57.1%), among them, 10 with hemocytopenia (58.82%), and 2 without hemocytopenia (50%). The positive rate of BMMNC Coombs test was higher in the patients with SLE than that in healthy controls, and was higher in SLE patients with hemocytopenia than that in healthy controls. There were no significant difference of BMMNC-Coombs positive rate between the SLE patients without hemocytopenia and healthy controls, and there were also no significant differences between the SLE patients without hemocytopenia and SLE patients with hemocytopenia. In the 12 SLE patients with positive BMMBC-Coombs tests, IgM auto-antibody accounted for 75.0%, and C3 50.0%, IgG 8.33%, IgG+IgM 8.33%, C3+IgM 16.67%, IgG+IgM+C3 16.67%. In the SLE patients without hemocytopenia, IgG+IgM accounted for 8.33%, C3 8.33%, but IgA autoantibody were not seen in any case. There was a significant positive correlation between the auto-antibodies on BMMNC and peripheral anti-SSA, but there was no significant correlation between the results of BMMBC Coombs tests and peripheral blood cell counts. Conclusion:There were auto-antibodies on BMMNC in the patients with SLE. The hemocytopenia in the patients with SLE maybe resulted from the destructions of bone marrow hematopoietic cells by the autoantibodies.

Collagen triple helix repeat containing-1: a novel biomarker associated with disease activity in Systemic lupus erythematosus

Lupus ◽

10.1177/0961203318804877 ◽

2018 ◽

Vol 27 (13) ◽

pp. 2076-2085 ◽

Cited By ~ 1

Author(s):

Q Wu ◽

Q Yang ◽

H Sun

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Triple Helix ◽

Inactive Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Systemic Lupus ◽

Sledai Score ◽

Collagen Triple Helix

Objective The objective of this article is to investigate whether the aberrant expression of collagen triple helix repeat containing-1 (CTHRC1) from patients with systemic lupus erythematosus (SLE) could contribute to the pathogenesis of lupus. Methods We divided SLE patients into active groups (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥ 6) and inactive groups (SLEDAI score < 6). Serum concentrations of CTHRC1, interferon alpha, interleukin (IL)-28A and IL-28B were determined using an enzyme-linked immunosorbent assay in a group of 40 patients with SLE. Results were compared with those from 23 healthy controls. Results Serum CTHRC1 protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease displayed higher CTHRC1 levels compared with those with inactive disease as well. There was a positive association between serum CTHRC1 levels and SLEDAI and erythrocyte sedimentation rate, and a negative correlation with complement 3 and 4. Moreover, serum CTHRC1 levels were higher in SLE patients with arthritis and anemia compared with patients without the above-mentioned manifestations. Conclusions These findings indicate CTHRC1 probably plays an important part in the pathogenesis of SLE, and is positively associated with disease activity, while it also likely refers to the development of arthritis and anemia in SLE. Therefore, CTHRC1 may provide a novel research target and shed new light on the pathogenesis and therapy of SLE.

The Regulatory B Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-analysis

Journal of Human Physiology ◽

10.30564/jhp.v2i1.1594 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Xiaohuan Chen ◽

Lei Liu ◽

Lei Liao ◽

Yahui Wang ◽

Jiacheng Shi ◽

...

Keyword(s):

Sensitivity Analysis ◽

Lupus Erythematosus ◽

Subgroup Analysis ◽

Meta Analysis ◽

Systemic Review ◽

Systemic Lupus ◽

Regulatory B Cell ◽

Sledai Score ◽

Background: The study of regulatory B cells (Bregs) in systemic lupus erythematosus (SLE) has been in full swing in recent years, but the number and function of Bregs in SLE patients have also present quite contradictory results. Therefore, we conducted a meta-analysis to verify the changes in Bregs in active SLE. Methods: We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed, Embase, Web of Science, Cochrane and CNKI. Due to the degree of heterogeneity is very high, we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls. Then, sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity. Results: Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis. The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls [0.259, (−1.150, 1.668), p = 0.719], with great heterogeneity ( I2 = 97.5%) . The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity, but after excluding the article conducted by Cai X and his colleagues, the percentages of Bregs were significantly higher in active SLE than those in controls [1.394, (0.114,2.675), p = 0.033]. The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score ≥ 5, the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739), p = 0.002], but when the threshold of SLEDAI score ≥ 6 chosen for active SLE, the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759), p < 0.001]. Meanwhile, other subgroup analysis based on the different phenotypes of Bregs, diagnostic criteria, enrolled research countries, treatment status, and organ involvement did not differ in proportion of Bregs between SLE patients and controls. Conclusions: The study implies that Bregs may play a role in the pathogenesis of active SLE, and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.

Apoptosis-derived membrane vesicles drive the cGAS–STING pathway and enhance type I IFN production in systemic lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-212988 ◽

2018 ◽

Vol 77 (10) ◽

pp. 1507-1515 ◽

Cited By ~ 29

Author(s):

Yasuhiro Kato ◽

JeongHoon Park ◽

Hyota Takamatsu ◽

Hachirou Konaka ◽

Wataru Aoki ◽

...

Keyword(s):

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Membrane Vesicles ◽

Guanosine Monophosphate ◽

Type I ◽

Healthy Controls ◽

Reporter System ◽

Systemic Lupus ◽

Sting Pathway

ObjectiveDespite the importance of type I interferon (IFN-I) in systemic lupus erythematosus (SLE) pathogenesis, the mechanisms of IFN-I production have not been fully elucidated. Recognition of nucleic acids by DNA sensors induces IFN-I and interferon-stimulated genes (ISGs), but the involvement of cyclic guanosine monophosphate (GMP)–AMP synthase (cGAS) and stimulator of interferon genes (STING) in SLE remains unclear. We studied the role of the cGAS–STING pathway in the IFN-I-producing cascade driven by SLE serum.MethodsWe collected sera from patients with SLE (n=64), patients with other autoimmune diseases (n=31) and healthy controls (n=35), and assayed them using a cell-based reporter system that enables highly sensitive detection of IFN-I and ISG-inducing activity. We used Toll-like receptor-specific reporter cells and reporter cells harbouring knockouts of cGAS, STING and IFNAR2 to evaluate signalling pathway-dependent ISG induction.ResultsIFN-I bioactivity and ISG-inducing activities of serum were higher in patients with SLE than in patients with other autoimmune diseases or healthy controls. ISG-inducing activity of SLE sera was significantly reduced in STING-knockout reporter cells, and STING-dependent ISG-inducing activity correlated with disease activity. Double-stranded DNA levels were elevated in SLE. Apoptosis-derived membrane vesicles (AdMVs) from SLE sera had high ISG-inducing activity, which was diminished in cGAS-knockout or STING-knockout reporter cells.ConclusionsAdMVs in SLE serum induce IFN-I production through activation of the cGAS–STING pathway. Thus, blockade of the cGAS–STING axis represents a promising therapeutic target for SLE. Moreover, our cell-based reporter system may be useful for stratifying patients with SLE with high ISG-inducing activity.

POS0784 AUDIOLOGIC EVALUATION IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS AND IMPACT OF HYDROXYCHLOROQUINE THERAPY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3742 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 645.2-645

Author(s):

S. Tharwat ◽

W. Elshawaf ◽

M. K. Nassar

Keyword(s):

Hearing Impairment ◽

Lupus Erythematosus ◽

Chronic Administration ◽

Healthy Controls ◽

Systemic Lupus ◽

High Frequency Audiometry ◽

Significant Difference ◽

Patient Reported ◽

The Impact

Background:Hydroxychloroquine (HCQ) is a commonly used agent in the treatment of rheumatic diseases including systemic lupus erythematosus (SLE). [1]Objectives:The aim of this study was to evaluate the hearing function in SLE patients and assess the impact of chronic HCQ.Methods:This study was carried out on 60 individuals (48 SLE and 12 healthy controls). The SLE patients were divided into HCQ group (n=36) and non-HCQ group (n=12) according to the chronic administration of HCQ. All participants were assessed by full audiological history and extended high frequency audiometry at frequencies 9, 10, 11, 2, 12.5, 14, 16,18 and 20 KHz.Results:When comparing the study SLE patients with healthy controls,there was a statistically significant difference regarding patient reported otological manifestations such as tinnitus (p=.021), vertigo (p=.002) and hearing impairment (p=.042) while there was no significant difference regarding deafness or ear buzzing in one or both ears. HCQ group showed more hearing impairment at frequency 9000 and 20000 Hz than non-HCQ group (p=.004, <.001 respectively).Conclusion:Otological symptoms and sensorineural hearing loss are prevalent among SLE patients. Chronic administration of HCQ may have an ototoxic effect.References:[1]Fiehn, C., et al. “Safety management in treatment with antimalarials in rheumatology. Interdisciplinary recommendations on the basis of a systematic literature review.” Zeitschrift für Rheumatologie (2020): 1-9.Figure 1.Otological manifestations in the study SLE patients (n=48) and the healthy controls (n=12)Disclosure of Interests:None declared

Circulating antioxidant levels in systemic lupus erythematosus patients: a systematic review and meta-analysis

Biomarkers in Medicine ◽

10.2217/bmm-2019-0034 ◽

2019 ◽

Vol 13 (13) ◽

pp. 1137-1152 ◽

Cited By ~ 1

Author(s):

Napoleon Bellua Sam ◽

Bao-Zhu Li ◽

Rui-Xue Leng ◽

Hai-Feng Pan ◽

Dong-Qing Ye

Keyword(s):

Systematic Review ◽

Serum Level ◽

Lupus Erythematosus ◽

Activity Index ◽

Meta Analysis ◽

Healthy Controls ◽

Systemic Lupus ◽

Precise Estimation ◽

Aim: To derive a precise estimation on plasma/serum level of SOD, GPx, CAT and GSH levels in systemic lupus erythematosus (SLE) patients. Methods: A total of 36 articles from electronic databases were finally included with 1120 SLE patients and 1024 healthy controls considered for antioxidant levels. Results: The levels of CAT and GSH were significantly lower, while SOD and GPx levels were slightly lower in patients with SLE compared with healthy controls. Subgroup analysis indicated that Arabs, ages ≥40 and SLE diseases activity index <6 had a significant association of SOD and CAT levels with SLE patients. Conclusion: The results demonstrated a significant lower CAT and GSH levels and also revealed no significant difference for SOD and GPx levels in SLE patients.

Deregulated NLRP3 and NLRP1 Inflammasomes and Their Correlations with Disease Activity in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.130310 ◽

2013 ◽

Vol 41 (3) ◽

pp. 444-452 ◽

Cited By ~ 41

Author(s):

Qingrui Yang ◽

Chengcheng Yu ◽

Zhaowen Yang ◽

Qing Wei ◽

Kun Mu ◽

...

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Activity Index ◽

Type I ◽

Healthy Controls ◽

Systemic Lupus ◽

Glucocorticoid Treatment ◽

Peripheral Blood Mononuclear

Objective.NOD-like receptor family, pyrin domain containing 3 and 1 (NLRP3 and NLRP1) inflammasomes are molecular platforms that sense the damage or danger signals of cells. We investigated whether NLRP3/NLRP1 inflammasomes are involved in the pathogenesis and progression of systemic lupus erythematosus (SLE).Methods.Expressions of inflammasome components at the mRNA and protein levels in the peripheral blood mononuclear cells (PBMC) from patients with SLE and healthy controls were investigated by quantitative real-time transcription PCR and Western blot, respectively. Correlations between NLRP3/NLRP1 inflammasome components’ expression and clinical disease progression were investigated. Expressions of NLRP3/NLRP1 inflammasomes before and after treatment in the patients with SLE were also analyzed and compared.Results.Our data showed that expressions of NLRP3/NLRP1 inflammasomes were significantly downregulated in PBMC from patients with SLE compared with PBMC from healthy controls. Further, expressions of NLRP3/NLRP1 inflammasomes were negatively correlated with the SLE Disease Activity Index, and regular glucocorticoid treatment significantly corrected this deregulation of these inflammasomes. Further analysis showed that type I interferon (IFN) level was significantly negatively correlated with expression of NLRP3/NLRP1 inflammasomes, which indicated that enhanced IFN-I level in patients with SLE was responsible, at least to a great degree, for the deregulation of inflammasomes.Conclusion.These results indicated deregulation of NLRP3/NLRP1 inflammasomes in patients with SLE, and suggested an important role for inflammasomes in the pathogenesis and progression of SLE.

Association of TNFAIP3 gene polymorphism (rs5029939) with susceptibility and clinical phenotype of systemic lupus erythematosus

Archives of Rheumatology ◽

10.46497/archrheumatol.2022.8769 ◽

2021 ◽

Vol 36 (4) ◽

pp. 570-576

Author(s):

Hala Gaballah ◽

Reham Abd-elkhalek ◽

Ola Hussein ◽

Shimaa Abd El-wahab

Keyword(s):

Gene Polymorphism ◽

Lupus Erythematosus ◽

Clinical Phenotype ◽

Association Studies ◽

Genome Wide Association Studies ◽

Genotype Distribution ◽

Healthy Controls ◽

Systemic Lupus ◽

Objectives: This study aims to investigate the association of the tumor necrosis factor-alpha inducible protein 3 (TNFAIP3) (rs5029939) gene single nucleotide polymorphism (SNP) with the risk of systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort of SLE patients. Patients and methods: This study included a total of 180 participants (18 males, 72 females; mean age: 30.9±10.1 years; range 17 to 59 years) including 90 SLE patients and 90 healthy controls between March 2017 and February 2020. The TNFAIP3 rs5029939 gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all participants. Results: There was a significant difference in genotype distribution of the TNFAIP3 rs5029939 SNP between SLE patients and healthy controls, where CG genotype was more common in SLE patients (53.3%) than controls (11.1%) (p=0.001). We found a significant difference in G allele frequency of TNFAIP3 (rs5029939) (37.8% with SLE vs. 5.6% with controls, p=0.001). Genotype CG was significantly associated with lupus nephritis and neuropsychiatric manifestations (p<0.05). Although the response to treatment was numerically higher with the genotype CC, it did not reach statistical significance (p=0.4). Conclusion: Our study suggests that TNFAIP3 rs5029939 gene polymorphism is associated with SLE susceptibility and may have an impact on its clinical phenotype. As such association differs among populations of diverse ethnic backgrounds, larger genome-wide association studies are warranted to further elucidate genetic associations.

Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.690908 ◽

2021 ◽

Vol 12 ◽

Author(s):

Aziz Farah Izati ◽

Nur Diyana Mohd Shukri ◽

Wan Syamimee Wan Ghazali ◽

Che Maraina Che Hussin ◽

Kah Keng Wong

Keyword(s):

Lupus Erythematosus ◽

Serum Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Immunological Parameters ◽

Th Cells ◽

Reactive Protein ◽

Dsdna Antibody ◽

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.