scholarly journals Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhuochao Zhou ◽  
Aining Xu ◽  
Jialin Teng ◽  
Fan Wang ◽  
Yun Tan ◽  
...  

Background. Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE. Methods. The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients ( n = 70 ), rheumatoid arthritis (RA) ( n = 24 ), primary Sjögren’s Syndrome (pSS) ( n = 21 ), and healthy controls (HCs) ( n = 70 ) using enzyme-linked immunosorbent assay (ELISA). The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results. The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to RA, pSS, and HCs (all p < 0.0001 ). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score ( r = 0.254 , p = 0.034 ), erythrocyte sedimentation rate (ESR) ( r = 0.430 , p < 0.001 ), C-reactive protein (CRP) ( r = 0.246 , p = 0.049 ), and immunoglobulin G (IgG) ( r = 0.408 , p = 0.001 ) and negatively associated with haemoglobin (Hb) ( r = − 0.294 , p = 0.014 ). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( p = 0.004 and 0.044, respectively) compared with unconjugated human IgG. Conclusions. These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE.

2020 ◽  
Author(s):  
Zhuochao Zhou ◽  
Aining Xu ◽  
Jialin Teng ◽  
Fan Wang ◽  
Yun Tan ◽  
...  

Abstract Backgroud: To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in systemic lupus erythematosus (SLE), we aimed to reveal the clinical relevance and impact of anti-Tyro3 antibody on SLE. Methods : The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients (n =70) and healthy controls (HCs) (n =70) using enzyme-linked immunosorbent assay (ELISA). The correlation of the levels of autoantibodies against Tyro3 receptor with clinical and laboratory characteristics were analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of anti-Tyro3 IgG for the diagnosis of SLE. The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results : The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to HCs ( p < 0.0001). The levels of anti-Tyro3 IgG were negatively associated with haemoglobin (Hb) ( r =-0.294, p = 0.014), and positively correlated with the presence of oral ulcers ( r = 0.254, p = 0.034), SLE disease activity index (SLEDAI) score ( r = 0.254, p = 0.034), erythrocyte sedimentation rate (ESR) ( r = 0.430, p = 0.000), C-reactive protein (CRP) ( r = 0.246, p = 0.049) and immunoglobulin G (IgG) ( r = 0.408, p = 0.001). Higher levels of anti-Tyro3 antibody were observed in patients with oral ulcers than paitents without oral ulcers ( p = 0.035). Further flow cytometry demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( p = 0.004). Immunofluorescence assay also showed a decreased engulfment of apoptotic cells in the macrophages incubated with purified anti-Tyro3 IgG ( p = 0.044) compared with control IgG. Conclusions: These observations indicated that autoantibody against Tyro3 was associated with disease activity and impaired efferocytosis of macrophages, which might be involved in the pathogenesis of SLE.


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.


2021 ◽  
Vol 10 (20) ◽  
pp. 4788
Author(s):  
Katarzyna Pawlak-Buś ◽  
Wiktor Schmidt ◽  
Piotr Leszczyński

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study aimed to identify associations between serum IL-27 and IL-23 levels and disease activity in Polish patients with different manifestations of SLE: neuropsychiatric lupus (NPSLE), and lupus nephritis (LN). Associations between interleukin levels and oligo-specific antibodies against double-stranded DNA (dsDNA), dose of glucocorticoids, and type of treatment were also analyzed. An enzyme-linked immunosorbent assay was used to assess anti-dsDNA antibodies and analyze the serum concentration of IL-27 and IL-23 from 72 patients aged 19–74 years with confirmed active SLE. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2-K). No significant correlations between interleukin levels and SLEDAI score, anti-dsDNA, corticosteroid dose, or type of treatment were noted. Patients with NPSLE and LN presented the highest median scores of SLEDAI.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Azita Sohrabian ◽  
Ioannis Parodis ◽  
Nellie Carlströmer-Berthén ◽  
Martina Frodlund ◽  
Andreas Jönsen ◽  
...  

Abstract Introduction Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value. Methods A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment. Results High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers. Conclusion Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.


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 58 (8) ◽  
pp. 1271-1281 ◽  
Author(s):  
Mônica Simon Prado ◽  
Alessandra Dellavance ◽  
Silvia Helena Rodrigues ◽  
Valdecir Marvulle ◽  
Luis Eduardo Coelho Andrade

AbstractBackgroundThe objective of the study was to determine whether the staining pattern and titer of indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) are associated with systemic lupus erythematosus (SLE) disease activity.MethodsA total of 269 consecutive patients meeting the ACR and SLICC criteria for SLE were classified into three groups according to the SLE Disease Activity Index 2000 (SLEDAI2K): Remission (SLEDAI2K = 0; n = 47); Intermediate (SLEDAI2K = 1-5; n = 111); Active (SLEDAI2K ≥ 6; n = 111). All subjects were assessed for HEp-2 IFA titer and staining pattern and nine traditional parameters of SLE disease activity. After a 6 to 12-month interval, 101 of the 269 patients were reassessed.ResultsHEp-2 IFA homogeneous nuclear pattern (AC-1) occurred more frequently in the Active Group compared to the Remission Group (p < 0.001). Fine speckled nuclear pattern (AC-4) tended to occur more frequently in the Remission Group compared to the Active Group (p = 0.054). Subjects with AC-1 pattern had higher SLEDAI (8.8 ± 7.6) than those with AC-4 (4.8 ± 5.2) (p < 0.001). HEp-2 IFA titer and anti-nuclear antibody by enzyme-linked immunosorbent assay (ANA-ELISA) values were lower in the Remission Group compared to the other two groups (p < 0.001). Multivariate analyses identified only ELISA anti-dsDNA as an independent variable associated with disease activity. In follow-up analysis, HEp-2 IFA titer decreased significantly in the 33 subjects with decreased disease activity (p = 0.002). Receiver operator characteristic (ROC) curve analysis for determination of disease activity showed equivalent areas under the curve (AUC) for HEp-2 IFA titer and traditional disease activity parameters.ConclusionsHEp-2 IFA pattern and titer can reflect SLE disease activity and may be considered in conjunction with other laboratory and clinical parameters in the assessment of SLE disease activity.


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.


2019 ◽  
Vol 8 (3) ◽  
pp. 204-210
Author(s):  
Mohammadreza Nakhjavani ◽  
Sima Abediazar ◽  
Amir Ghorbanihaghjo ◽  
Niloofar Esmaeili ◽  
Tala Pourlak ◽  
...  

Introduction: Lupus nephritis (LN) is one of the most severe signs of systemic lupus erythematosus (SLE) and rapid diagnosis of kidney damage remains an important concern for LN. Objectives: The aim of this study was to investigate the association of the serum levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and interleukin 17 (IL-17) with SLE severity, renal involvement, and other clinical manifestations in lupus patients. Patients and Methods: In order to determine a better biomarker for the detection of renal damage, this study evaluated the ability of serum TWEAK (sTWEAK) and IL-17 in lupus patients with (n=25) and without (n=25) nephritis and healthy controls (n=39). Moreover, it compared the levels of these cytokines with disease activity and chronicity as well as traditional serum markers including complement C3 and C4, creatinine, and proteinuria in lupus patients. Results: Increased levels of sTWEAK and IL-17 were observed in SLE and LN groups compared to healthy controls and non-LN groups, respectively. Significant positive associations were observed between serum TWEAK and IL-17 levels and systemic lupus erythematosus disease activity index (SLEDAI), proteinuria, nephritis activity index, and some clinical manifestations (P<0.05). Discriminating the ability of the studied cytokines were not better than the utility of any markers individually. Conclusion: The serum levels of TWEAK and IL-17 in the SLE and LN groups were significantly higher than the control group and both markers were indicative of the renal disease severity; therefore, they could possibly indicate renal involvement in the lupus patients.


2014 ◽  
Vol 132 (4) ◽  
pp. 239-242 ◽  
Author(s):  
Thelma Larocca Skare ◽  
Kellen Ferri ◽  
Marcela Aimone Santos

CONTEXT AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with a cyclical clinical course. Evaluation of the clinical activity of this disease is important for choosing the correct treatment. The objective of this study was to analyze the value of beta-2 microglobulin (β2M) serum levels in determining SLE clinical activity.DESIGN AND SETTING: Cross-sectional analytical study conducted at the rheumatology outpatient clinic of a private university hospital.METHODS: 129 SLE patients were studied regarding disease activity using SLEDAI (SLE Disease Activity Index) and cumulative damage using SLICC ACR (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE). At the same time, the β2M serum level, ESR (erythrocyte sedimentation rate), anti-dsDNA (anti-double-stranded DNA) and C3 and C4 complement fractions were determined.RESULTS: β2M levels correlated positively with SLEDAI (P = 0.02) and ESR (P = 0.0009) and negatively with C3 (P = 0.007). Patients who were positive for anti-dsDNA had higher β2M serum levels (P = 0.009).CONCLUSION: β2M levels are elevated in SLE patients with active disease.


2020 ◽  
Vol 9 (11) ◽  
pp. 3563
Author(s):  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Yuya Fujita ◽  
Haruki Matsumoto ◽  
Jumpei Temmoku ◽  
...  

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.


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