scholarly journals Chemokine CXCL1 as a potential marker of disease activity in systemic lupus erythematosus

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanli Zeng ◽  
Qiaoduan Lin ◽  
Liang Yu ◽  
Xuelian Wang ◽  
Yiqiang Lin ◽  
...  

Abstract Objectives The chemokine CXCL1, known as growth-related oncogene α (GRO-α), is a potent chemoattractant and regulator of neutrophils. The purpose of our study was to evaluate the regulatory response of CXCL1 in the serum of patients with systemic lupus erythematosus (SLE) in the active stage of disease and to assess whether it was implicated in the pathogenesis/inflammatory process in lupus. Methods CXCL1 serum concentrations were examined in 90 SLE patients, 56 other autoimmune diseases (OADs) patients and 100 healthy controls using enzyme-linked immunosorbent methodology. Results SLE patients exhibited significant increases in serum CXCL1 concentrations [1492.86 (735.47–2887.34) pg/ml] compared with OADs patients [155.88 (10.77–366.78) pg/ml] and healthy controls [13.58 (8.46–37.22) pg/ml] (p < 0.001). Moreover, the level of CXCL1 decreased as the level of anti-dsDNA IgG decreased after treatment between the anti-dsDNA-positive SLE patients and the anti-dsDNA-negative SLE patients. Additionly, serum CXCL1 concentrations were related to different disease activity levels in SLE and lupus nephritis (LN) and high avidity of IgG ANAs (HA IgG ANAs) (p < 0.05). Furthermore, CXCL1 serum concentrations were significantly correlated with the SLE Disease Activity Index(SLEDAI) score, relative avidity index (RAI) of HA IgG ANAs and the levels of anti-dsDNA IgG, CRP, ESR, albumin, C3 and C4.Additionally, Statistical analysis revealed that positivity for IgG ANA (p < 0.001), the presence of HA IgG ANAs (p = 0.001) and the logarithmic level of anti-dsDNA IgG (p = 0.021) were significantly associated with the logarithmic level of CXCL1 with standard partial regression coefficients (95% CI) of 2.371 (1.734–3.009), 1.231 (0.52–1.937) and 0.409 (0.062–0.755), respectively. Finally, using cutoff points of 1182.17 pg/mL and 1500.31 pg/mL, serum CXCL1 levels had a similar sensitivity of 76% and specificity of 100% and 75% for the diagnosis of active SLE and LN, respectively. Conclusions Serum CXCL13 concentrations might represent a potential marker of disease activity in systemic lupus erythematosus.

Lupus ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 748-754 ◽  
Author(s):  
R C Li ◽  
J Guo ◽  
L C Su ◽  
A F Huang

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.


Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.


2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Ting Zhang ◽  
Yong Du ◽  
Qingqing Wu ◽  
Hao Li ◽  
Thao Nguyen ◽  
...  

Abstract Objectives To assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations. Methods Saliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated. Results Salivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p < 0.001). Among ANA-positive samples, 80.85% exhibited a nuclear ANA pattern, and 42.55% exhibited a cytoplasmic ANA pattern. Salivary IgG-ANA, IgA-ANA, and IgM-ANA levels, as assayed by ELISA, were significantly increased in both active and less active SLE patients compared with healthy controls, and levels of each isotype were significantly correlated with serum ANA titer. Salivary IgM-ANA levels correlated with the physician global assessment (PGA), SLE disease activity index (SLEDAI), and negatively with serum C3 and C4. Salivary IgG-ANA also correlated with erythrocyte sedimentation rate (ESR), SLEDAI, and negatively with serum C3. Conclusion Salivary ANA levels correlate with serum ANA titer, and salivary IgM-ANA and IgG-ANA correlate variably with PGA, SLEDAI, ESR and complement levels. These findings underscore the potential of using salivary ANA and ANA isotypes as surrogates for serum ANA, particularly for future point-of-care applications since saliva is easier to obtain than blood.


Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1074-1081 ◽  
Author(s):  
I Cavazzana ◽  
R Kumar ◽  
C Pozzari ◽  
R Ottaviani ◽  
M Fredi ◽  
...  

Objective The objective of this study was to analyse autoantibodies’ titres modulation during belimumab treatment in 50 patients with systemic lupus erythematosus (SLE). Methods Sera were collected at belimumab start (T0) and every six months until the 24th month. Disease activity index (SLEDAI-2K) was analysed at every timepoint. High avidity anti-dsDNA was detected by radioimmunological method, anti-ENA, anti-cardiolipin antibodies (aCL), anti-β2 glycoprotein I (anti-β2GPI) were analysed by ELISA. Results Fifty patients with SLE (mean SLEDAI-2K: 7.18 ± :3), mean age of 39 ± 11 years and mean follow-up of 13 ± 7.8 years were enrolled. A significant decrease of anti-dsDNA and anti-β2GPI IgM titres was observed at all timepoints. IgG aCL titre showed significant decrease only at T18. Anti-dsDNA negativization was detected in 21%, anti-β2GPI IgG in 33% and aCL IgG in 30% of sera, mostly at T6. Anti-ribosomal showed a significant titre decrease at T6 and T12, with negative seroconversion at T18. Anti-Sm titre significantly dropped down at T6, then remained stable during the time. Significant correlations were found between anti-dsDNA and anti-ribosomal titre and between SLEDAI ratio (SLEDAI value/SLEDAI T0) and anti-ribosomal titre ratio (value/value T0). Conclusions Belimumab treatment induced a significant reduction of SLE-specific autoantibodies titre and IgM anti-β2GPI. Anti-ribosomal titre decrease correlates with anti-dsDNA titre and disease activity improvement.


Author(s):  
Chayanika Dutta ◽  
Sanjeeb Kakati ◽  
Bhupen Barman ◽  
Kaustubh Bora

Abstract Background The importance of vitamin D (VD) in systemic lupus erythematosus (SLE) is being increasingly appreciated, with studies suggesting a relationship between VD deficiency and SLE onset/disease activity. We investigated VD status in SLE patients and its associations with disease activity in a geographical region of India receiving low solar ultraviolet-B (UV-B) index. Materials and methods We enrolled 109 SLE patients along with 109 healthy controls belonging to same ethnicity and localities. Demographic and clinico-laboratory information were recorded. VD status was assessed by estimating serum 25-hydroxyvitamin D (25-OH-D) concentrations (deficient: <20 ng/mL, insufficient: 21–29 ng/mL, and sufficient/normal: ≥30 ng/mL) using an enzyme-linked fluorescent assay (ELFA). The SLE Disease Activity Index (SLEDAI) scoring system was used to evaluate disease activity. The association between VD status and disease activity was assessed by univariate and multivariate approaches. Results Hypovitaminosis D was prevalent in 90.83% SLE patients [vs. 77.98% healthy controls; chi-squared (χ2) = 10.125, df = 2, p < 0.01]. SLEDAI scores and 25-OH-D values were inversely associated, which extended in a two-way manner as revealed by multiple logistic regression models. SLE patients with VD deficiency were more likely to have high/very high disease activity [adjusted odds ratio (OR) = 3.5, 95% confidence intervals (CI): 1.4–8.9]. Conversely, patients with high SLEDAI scores (>10) also had greater risks of being VD deficient (adjusted OR = 3.9, 95% CI: 1.5–10.8). Conclusion VD deficiency is widespread in SLE. The relationship appears to be bidirectional, with VD status associated both as determinant and outcome of disease activity in SLE.


2021 ◽  
Vol 1 ◽  
pp. 118-123
Author(s):  
Faiq Isho Gorial ◽  
Hameed Oda Ali ◽  
Sattar Jabbar Naema ◽  
Saad Abdurahman Hussain

Background: The link between red blood cell distribution width-to-platelet ratio (RPR) and disease activity in systemic lupus erythematosus (SLE) is not well understood. Aim:  To investigate the association between RPR levels and disease activity in SLE. Methods: This was a case-control study conducted at Baghdad Teaching Hospital, Medical City from July 2020 to March 2021. Seventy SLE patients were compared with 70 healthy controls. The diagnosis was made using the American College of Rheumatology SLE criteria. Results: SLE patients had a mean age of 35.2±12.03 years, while controls had a mean age of 36.3±9.9 years (P=0.5). Females represent 97.1% of SLE patients and 88.6% of controls. The average disease duration was 4.98±0.05 years. The disease activity index (SLEDI) was 16.4±4.8. SLE patients had a lower platelet count than controls, and the median (IQR) of RDW was larger than that of controls. SLE patients had a greater median (IQR) of RPR than controls (0.058; 0.04-0.07 vs. 0.045; 0.039-0.053). The RPR and SLEDAI showed strong positive association. The optimal cutoff point for distinguishing SLE patients from controls was 0.0455, with 79% sensitivity and 51% specificity. The RPR was not significantly affected by sociodemographic or clinical factors. Conclusion: The RPR was positively correlated with disease activity in SLE patients, and may be a valid measure to differentiate between SLE patients and healthy controls. Sociodemographic and other clinical characteristics do not significantly affect RPR.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 345.2-346
Author(s):  
K. Nay Yaung ◽  
J. G. Yeo ◽  
M. Wasser ◽  
P. Kumar ◽  
S. P. Tang ◽  
...  

Background:Systemic lupus erythematosus (SLE) is a complex, systemic autoimmune disease that interferes with the balance between regulation and immunity, resulting in immune system dysfunction. Disease course is unpredictable due to alternating remissions and flares1.Disease activity and treatment response are measured with composite scores such as the SLE Disease Activity Index (SLEDAI)2. However, disease heterogeneity can impede reliable patient assessments. Mechanistic insights into SLE are required for better assessment.Current studies are mainly descriptive, and a complex disease like SLE is best interrogated with multi-parametric, holistic approaches such as mass cytometry (CyTOF).Objectives:(1)To characterise immune signatures of newly diagnosed SLE patients and in the process:a.Study the roles of B and T cells in SLEb.Gain a holistic understanding of the adaptive immune response(2)To compare immunological profiles of newly diagnosed SLE patients with age-matched healthy controlsWe hypothesise that significant differences exist between immunomes of newly diagnosed SLE and healthy subjects.Methods:Peripheral blood mononuclear cells (PBMCs) of 5 SLE subjects (median age 125 months) were tested with CyTOF. Data was uploaded to an online analytical platform, the Extended Polydimensional Immunome Characterization (EPIC) discovery tool, for comparison with 51 age-matched controls in its database.Subsequently, normalization and FlowSOM (Flow cytometry analysis by Self-Organising Maps) clustering to 50 nodes were performed with 37 functionally and phenotypically important immune markers. The Mann-Whitney U test identified significantly different cluster frequencies.Results:Correspondence analysis comparing global differences in cluster frequencies showed segregation of SLE subjects away from healthy controls. Multiple significant differences were identified (p < 0.05). Notably, a memory CD4+CD152+PD1+T cell subset (CD4+CD152+PD1+CD45RO+CD25-FoxP3-) was enriched in SLE (median: 2.17%, interquartile range: 1.66 to 7.74% of CD45+ PBMCs) versus control (1.34%, 1.06 - 1.58%; p = 0.00267). Expression of these known checkpoint inhibitors (PD1, CD152) could be important for SLE immunopathogenesis.Secondly, the innate lymphoid cell 2 (ILC2) subset (Lin-CD7+CD25+CD127+GATA3+) was markedly depressed in SLE (0.11%, 0.1 - 0.255%) versus control (0.41%, 0.25 - 0.55%; p = 0.0293). ILC2s protect epithelial integrity; a reduction suggests impaired protective roles in SLE.Supervised cell frequencies from bivariate analysis correlate strongly with unsupervised cell frequencies, validating these results (Pearson’s correlation coefficient r = 0.9926, p < 0.001 (CD4+CD152+PD1+CD45RO+CD25-FoxP3-); r = 0.8863, p < 0.05 (ILC2)).Conclusion:With a multi-parametric, unbiased approach comparing SLE subjects to a large database of age-matched healthy controls, we identified two immune subsets of potential immunopathogenic importance. With this information, the CyTOF panel can be redesigned to probe more specifically into the SLE immunome, facilitating disease-specific interrogation.References:[1]Tsokos,G.C. (2011). Systemic lupus erythematosus.N Engl J Med365(22), 2110-2121.[2]Bombardier, C., Gladman, D.D., Urowitz, M.B., Caron, D., Chang, C.H. (1992). Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE.Arthritis Rheum35(6), 630-640.Disclosure of Interests: :None declared


2013 ◽  
Vol 41 (3) ◽  
pp. 444-452 ◽  
Author(s):  
Qingrui Yang ◽  
Chengcheng Yu ◽  
Zhaowen Yang ◽  
Qing Wei ◽  
Kun Mu ◽  
...  

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.


2016 ◽  
Vol 43 (9) ◽  
pp. 1657-1664 ◽  
Author(s):  
Claudia Mora ◽  
Jorge Medina-Rosas ◽  
Ana Maria Santos ◽  
Diego A. Jaimes ◽  
Ana M. Arbeláez ◽  
...  

Objective.There are no laboratory tools that detect early flares in systemic lupus erythematosus (SLE). Our aim was to validate in our population the previous findings of the association of C4d-bearing reticulocytes (R-C4d) compared to anti-dsDNA antibodies, with disease activity assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) 2004 scales.Methods.All patients who met the 1987 American College of Rheumatology classification criteria and were seen consecutively in 2013 at a specialized SLE care clinic were included. Disease activity was established by the SELENA-SLEDAI and BILAG 2004. Anti-dsDNA and R-C4d were quantified in peripheral blood. Comparisons were made between values of active and inactive patients, and the correlations between the SELENA-SLEDAI and serum levels of anti-dsDNA and R-C4d were measured.Results.Sixty-two patients (83.9% women) were included. A total of 32.3% had active disease according to the SELENA-SLEDAI. There was a significant statistical difference (p = 0.0001) in the distribution of R-C4d between disease activity groups. The correlation coefficient between R-C4d and the SELENA-SLEDAI score was rs = 0.738 (p = 0.0001). R-C4d differed between patients with and without activity in the BILAG 2004 constitutional, mucocutaneous, gastrointestinal, renal, and hematological domains.Conclusion.R-C4d showed a higher correlation with SLE activity measured by the SELENA-SLEDAI and BILAG 2004 than anti-dsDNA did, suggesting a possible involvement in diagnosing disease activity. Prospective studies that confirm these findings and evaluate its involvement in followup are needed.


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