scholarly journals CD14 (C-159T) polymorphism is associated with increased susceptibility to SLE, and plasma levels of soluble CD14 is a novel biomarker of disease activity: A hospital-based case-control study

Lupus ◽  
2020 ◽  
pp. 096120332097279
Author(s):  
Aditya K Panda ◽  
Rina Tripathy ◽  
Bidyut K Das

Background Cluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (−159 C > T) with susceptibility to SLE or disease severity needs to be defined. Methods Two hundred female SLE patients diagnosed on systemic lupus international collaborating clinics (SLICC) classification criteria and age, sex, matched healthy controls were enrolled in the present study. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by enzyme-linked immunosorbent assay (ELISA). Results Prevalence of mutant genotypes (CT and TT) and minor allele (T) of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT: P < 0.0001; OR = 3.26, TT:P < 0.0001; OR = 3.39; T:P = 0.0009, OR = 1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P = 0.0002, OR = 8.07; T: P = 0.001, OR = 1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLE disease activity index-2K (SLEDAI-2K) scores and 24 hours proteinuria. Conclusion CD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.

2020 ◽  
Author(s):  
Aditya K Panda ◽  
Rina Tripathy ◽  
Bidyut K Das

ABSTRACTBackgroundCluster of differentiation 14 (CD14) plays a crucial role in the innate immune response of the host in protection against various pathogens. The importance of soluble CD14 in autoimmune disorders has been described in different populations. However, the role of sCD14 in systemic lupus erythematosus (SLE) is poorly understood. Further, the association of functional variants at the promoter region of the CD14 gene (−159 C>T) with susceptibility to SLE or disease severity needs to be defined.MethodsTwo hundred female SLE patients diagnosed on SLICC classification criteria and age, sex, matched healthy controls were enrolled in the present study. PCR-RFLP method was used to genotype CD14 (C-159 T) polymorphism. Plasma levels of IFN-α, TNF-α, and sCD14 were quantified by ELISA.ResultsPrevalence of mutant genotypes (CT and TT) and minor allele of CD14 (C-159T) polymorphism was significantly higher in SLE cases compared to healthy controls (CT:P<0.0001; OR=3.26, TT:P<0.0001; OR=3.39; T:P=0.0009, OR=1.62). Further, lupus nephritis patients had a higher prevalence of homozygous mutants (TT) and mutant allele (T)(TT: P=0.0002, OR=8.07; T: P=0.001, OR=1.32). SLE patients displayed significantly increased plasma sCD14, TNF-α, and IFN-α levels in comparison to healthy controls. These cytokines were significantly elevated in patients of lupus nephritis compared to those without kidney involvement. Interestingly, sCD14 levels correlated positively with SLEDAI-2K scores and 24 hours proteinuria.ConclusionCD14 (C-159T) polymorphism is associated with an increased predisposition to the development of SLE and lupus nephritis: sCD14 is a promising novel biomarker for assessing disease activity and lupus nephritis.


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.


Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2076-2085 ◽  
Author(s):  
Q Wu ◽  
Q Yang ◽  
H Sun

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.


2021 ◽  
Author(s):  
Xiaofei Lai ◽  
Huiqing Yang ◽  
Hao Ding ◽  
Ju Cao

Abstract Objective To investigate the association between Thymic stromal lymphopoietin (TSLP) and disease activity in patients with Systemic Lupus Erythematosus (SLE).Methods In this study, concentrations of serum TSLP in 65 SLE patients, 50 sex and age-matched control subjects were determined by enzyme-linked immunosorbent assay (ELISA).Results Serum TSLP concentrations in SLE patients were dramatically higher than healthy controls. The levels of serum TSLP displayed a significant increase as compared with healthy controls. More importantly, TSLP levels were significantly correlated with SLE disease activity features such as ESR, CRP, Anti-dsDNA Ab, and SLEDAI-2K,. The predictive value of TSLP on high disease activity was superior to those of CRP, ESR, and Anti-dsDNA Ab. A note worthy correlation in our study was observed between the serum TSLP levels and laboratory parameters, particularly serum lipids. Furthermore, serum TSLP levels could be significantly down-regulated after effective integrative treatment.Conclusion TSLP may serve as a novel sensitive biomarker to assist disease activity assessment and monitor therapeutic effects in active SLE patients.


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.


2020 ◽  
Vol 9 (4) ◽  
pp. 970
Author(s):  
Tim Dierckx ◽  
Laurent Chiche ◽  
Laurent Daniel ◽  
Bernard Lauwerys ◽  
Johan Van Weyenbergh ◽  
...  

Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement. Methods: Serum GlycA was measured by nuclear magnetic resonance spectroscopy in samples from well characterized SLE patients and from both healthy controls and patients with other kidney diseases (KD). Disease activity was evaluated using the Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K). Renal severity was assessed by kidney biopsy. Results: Serum GlycA was elevated in active (n = 105) compared to quiescent SLE patients (n = 39, p < 10−6), healthy controls (n = 20, p = 0.009) and KD controls (n = 21, p = 0.04), despite a more severely altered renal function in the latter. GlycA level was correlated to disease activity (SLEDAI-2K, ρ = 0.37, p < 10−4), C-reactive protein, neutrophil count, triglyceride levels, proteinuria and inversely to serum albumin. In patients with biopsy-proven lupus nephritis (LN), GlycA levels were higher in proliferative (n = 26) than non-proliferative LN (n = 10) in univariate analysis (p = 0.04), and was shown to predict proliferative LN independently of renal parameters, immunological activity, neutrophil count and daily corticosteroid dosage by multivariate analysis (p < 5 × 10−3 for all models). In LN patients with repeated longitudinal GlycA measurement (n = 11), GlycA varied over time and seemed to peak at the time of the flare. Conclusions: GlycA, as a summary measure for different inflammatory processes, could be a valuable biomarker of disease activity in patients with SLE, and a non-invasive biomarker of pathological severity in the context of LN.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Jia ◽  
Lingling Zhao ◽  
Chunyan Wang ◽  
Jin Shang ◽  
Yi Miao ◽  
...  

Objectives. We aimed to evaluate the value of immunoglobulin (Ig) G, IgM, and IgA isotypes of anti-double-stranded DNA (anti-dsDNA) and anti-C1q antibody in diagnosing systemic lupus erythematosus (SLE) patients and elucidate their association with disease activity and lupus nephritis. Methods. Blood samples were obtained from 96 SLE patients, 62 other autoimmune disease patients, and 60 healthy blood donors. Anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody were measured by enzyme-linked immunosorbent assay. Disease activity of SLE patients was assessed according to the SLE Disease Activity Index score. Results. When specificity was greater than 90%, the sensitivity of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody in diagnosing SLE was 75%, 45%, 33%, and 49%, respectively. The prevalence of anti-dsDNA IgG (p=0.002), anti-dsDNA IgA (p=0.028), and anti-C1q antibody (p=0.000) in active cases was significantly higher than those in inactive ones. In addition, the presence of anti-C1q antibody was associated with renal involvement (p=0.032). Anti-dsDNA IgM showed no significant association with disease activity, but it was inversely linked with lupus nephritis (p=0.005). When anti-dsDNA IgG and IgA and anti-C1q were combined to evaluate SLE disease activity, the specificity reached the highest level (90%). When anti-C1q positive was accompanied by anti-dsDNA IgM negative, the specificity of diagnosing lupus nephritis was up to 96%. Conclusions. This study demonstrated the role of anti-dsDNA IgG, IgM, and IgA isotypes and anti-C1q antibody alone or combination in diagnosing SLE. Anti-dsDNA IgG and IgA and anti-C1q were shown to be associated with disease activity, while anti-dsDNA IgM and anti-C1q were associated with lupus nephritis. When the related antibodies were combined, the diagnostic specificity was significantly higher.


Lupus ◽  
2017 ◽  
Vol 26 (5) ◽  
pp. 478-483 ◽  
Author(s):  
A T Lapa ◽  
M Postal ◽  
N A Sinicato ◽  
B S Bellini ◽  
PT Fernandes ◽  
...  

Objective To investigate serologic S100β protein levels in childhood-onset SLE patients (cSLE) and to elucidate their association with disease activity and neuropsychiatric (NP) manifestations. Methods We included 71 cSLE patients (67 females; median age 18 years; range 9–37 and 53 (47 females; median age of 20 years; range 6–29) age and sex matched healthy controls. Neurological manifestations were analysed according to the American College of Rheumatology (ACR) criteria. Cognitive evaluation was performed in all participants using Wechsler Intelligence Scale for Children (WISC-III) and Wechsler Adult Intelligence Scale (WAIS), according to age, and validated in Portuguese. SLE patients were further assessed for clinical and laboratory SLE manifestations, disease activity (SLE Disease Activity Index (SLEDAI)), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) and current drug exposures. Sera S100β protein levels were measured by enzyme-linked immunosorbent assay using commercial kits. Results The median S100β protein level was 116.55 pg/mL (range 1.53–468.50) in cSLE and 54.98 pg/mL (range 0.69–181.00) in healthy controls ( p < 0.001). An association was observed between S100β protein and NP manifestations ( p = 0.03). The S100β protein levels was associated with cognitive impairment in cSLE patients ( p = 0.006). Conclusions S100β protein levels are increased in cSLE with cognitive impairment. S100β may be considered a potential biomarker that underlies central nervous system (CNS) dysfunction, especially cognitive impairment.


2020 ◽  
Author(s):  
Risa Wakiya ◽  
Kiyo Ueeda ◽  
Shusaku Nakashima ◽  
Hiromi Shimada ◽  
Tomohiro Kameda ◽  
...  

Abstract Background: We investigated the effects of add-on hydroxychloroquine (HCQ) therapy on the expression of proinflammatory cytokines and other factors in systemic lupus erythematosus (SLE) patients with low disease activity.Methods: Patients who had low disease activity of at least 3 months duration were included. Patients with a history of lupus nephritis (LN+) must have been in remission for at least 3 months prior to enrollment. Serum levels of interferon interferon-α, S100A8, S100A9, tumor necrosis factor(TNF) -α, interleukin(IL)-2, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, Monocyte Chemotactic Protein-1, macrophage inflammatory protein-1α, IL-1β, Interleukin 1 receptor antagonist(IL-1ra), and Granulocyte Colony Stimulating Factor were measured immediately before and 3 months after treatment with oral HCQ treatment.Results: Of the 42 patients enrolled in the study (4 males, 38 females, mean age ± standard deviation age 41.4±13.3 years), 19 patients had a history of lupus nephritis but were currently in remission (LN+), and the remaining 23 patients had no history of LN (LN−). Serum levels of IL-1ra, S100A8, and S100A9 at baseline were significantly higher in the LN+ group compared with the LN− group (p=0.0092, p=0.012, and p=0.0043, respectively). In the full cohort, HCQ treatment led to significantly reduced serum levels of TNF-α, IL-6, VEGF-A, IL-1ra, IL-2, S100A8, and S100A9, and to decreased, albeit not significantly, levels of IL-8 and MIP-1α. The HCQ-induced changes in serum IL-8, IL-1ra, S100A8, and S100A9 levels were greater for patients in the LN+ group than those in the LN−group (p=0.0039, p=0.0011, p=0.0201, and p=0.0092, respectively). Conclusion: Add-on HCQ treatment decreased several proinflammatory cytokines levels in SLE patients with low disease activity, especially those with LN. The ability of HCQ to reduce IL-8 levels in patients with a history of LN suggests that HCQ treatment may improve the prognosis of LN.


2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Di Zhao ◽  
Xiao Yang ◽  
Jie Zhang ◽  
Yi Zhang

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been found to play important roles in systemic lupus erythematosus (SLE), however, whether Tim-3 is involved in apoptosis of NK cells in SLE remains unknown. The proportion of CD3−CD56+ NK cells and the percentage of AnnexinV+ NK cells were analyzed by flow cytometry in SLE patients and healthy controls. Tim-3 expression on NK cells was also evaluated by flow cytometry. We firstly observed a decreased proportion of NK cells and an increased proportion of apoptotic NK cells in SLE patients. The proportion of apoptotic NK cells was positively correlated with anti-dsDNA and SLEDAI. Tim-3 expression on NK cells was up-regulated in SLE patients. Further analysis showed that Tim-3 expression on NK cells was negatively correlated with the proportion of apoptotic NK cells, anti-dsDNA and SLEDAI, while positively correlated with the proportion of NK cells. The present results suggest that Tim-3 might play roles in SLE by regulating the apoptosis of NK cells and Tim-3 might serve as a potential target for the treatment of SLE.


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