Serum soluble toll‐like receptor 2: a novel biomarker for systemic lupus erythematosus disease activity and lupus‐related cardiovascular dysfunction

Houssen, Maha E.; El-Mahdy, Rasha H.; Shahin, Dina

doi:10.1111/1756-185x.12452

Cited by 26 publications

(25 citation statements)

References 28 publications

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“…We report, for the first time, that serum sTLR2 levels are significantly elevated in MS patients compared to match HC (Figure 1 A). This is consistent with observations of increased serum sTLR2 in a number of other inflammatory diseases and disease models, including severe bacterial infection ( 38 ), experimental human endotoxemia ( 32 ), and the autoimmune disease systemic lupus erythematosus, where it serves as a biomarker of disease activity ( 29 ). Notably, sTLR2 can act as a decoy microbial receptor since it retains the capacity to bind with the PAMPs as well as TLR2 coreceptor CD14, thereby preventing surface TLR2 to bind with CD14 and PAMPs.…”

Section: Discussionsupporting

confidence: 90%

“…As it has been reported that serum sTLR2 is a biomarker of recent infection, and of disease activity in other conditions, we measured sTLR2 levels in serum samples from MS patients in relapse and remission and compared them with those from HC ( 29 , 30 ). We observed significantly higher levels of sTLR2 in the serum samples of MS patients both during relapse (0.87 ng/ml) and remission (0.85 ng/ml) when compared with HC (0.58 ng/ml) (Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

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The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker

et al. 2018

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Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. It was previously shown that toll-like receptor (TLR)-2 signaling plays a key role in the murine experimental autoimmune encephalomyelitis (EAE) model of MS, and that TLR2-stimulation of regulatory T cells (Tregs) promotes their conversion to T helper 17 (Th17) cells. Here, we sought potential sources of TLR2 stimulation and evidence of TLR2 activity in MS patient clinical samples. Soluble TLR2 (sTLR2) was found to be significantly elevated in sera of MS patients (n = 21), in both relapse and remission, compared to healthy controls (HC) (n = 24). This was not associated with the acute phase reaction (APR) as measured by serum C-reactive protein (CRP) level, which was similarly increased in MS patients compared to controls. An independent validation cohort from a different ethnic background showed a similar upward trend in mean sTLR2 values in relapsing-remitting MS (RRMS) patients, and significant differences in sTLR2 values between patients and HC were preserved when the data from the two cohorts were pooled together (n = 41 RRMS and 44 HC, P = 0.0006). TLR2-stimulants, measured using a human embryonic kidney (HEK)-293 cells transfectant reporter assay, were significantly higher in urine of MS patients than HC. A screen of several common urinary tract infections (UTI)-related organisms showed strong induction of TLR2-signaling in the same assay. Taken together, these results indicate that two different markers of TLR2-activity—urinary TLR2-stimulants and serum sTLR2 levels—are significantly elevated in MS patients compared to HC.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker

et al. 2018

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“…They are capable of ligand (PAMPs and DAMPs) binding, but do not transmit the signal downstream [ 2 ]. Elevated serum levels of sTLR4 are associated with infection, predominately with bacterial, while decreased levels of sTLR2 are associated with autoimmune diseases [ 3 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage

et al. 2016

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BackgroundToll-like receptor (TLR) signalling begins early in subarachnoid haemorrhage (SAH), and plays a key role in inflammation following cerebral aneurysm rupture. Available studies suggest significance of endogenous first-line blockers of a TLR pathway—soluble TLR2 and 4.MethodsEighteen patients with SAH and acute hydrocephalus underwent endovascular coiling and ventriculostomy; sTLR2 and 4 levels were assayed in cerebrospinal fluid (CSF) collected on post-SAH days 0–3, 5, and 10–12. Release kinetics were defined. CSF levels of sTLR2 and 4 were compared with a control group and correlated with the clinical status on admission, the findings on imaging, the degree of systemic inflammation and the outcome following treatment.ResultsNone of study group showed detectable levels of sTLR2 and 4 on post-SAH day 0–3. 13 patients showed increased levels in subsequent samples. In five SAH patients sTLR2 and 4 levels remained undetectable; no distinctive features of this group were found. On post-SAH day 5 the strongest correlation was found between sTLR2 level and haemoglobin level on admission (cc = -0.498, P = 0.037). On post-SAH day 10–12 the strongest correlation was revealed between sTLR2 and treatment outcome (cc = -0.501, P = 0.076). Remaining correlations with treatment outcome, status at admission, imaging findings and inflammatory markers on post-SAH day 5 and 10–12 were negligible or low (-0.5 ≤ cc ≤ 0.5).ConclusionsIn the majority of cases, rupture of a cerebral aneurysm leads to delayed release of soluble TLR forms into CSF. sTLR2 and 4 seem to have minor role in human post-SAH inflammation due to delayed release kinetics and low levels of these protein.

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“…It is noteworthy that a novel observation revealed by Houssen et al, is the negative correlation between serum soluble TLR2 (sTLR2) levels and SELDAI score in SLE patients. This negative correlation was attributed to the role of sTLR2 in down regulation of TLR2 signaling through various mechanisms [23].…”

Section: Discussionmentioning

confidence: 99%

Expression of TLR2 and TLR4 on CD14 Monocytes in Female SLE Patients E

Fawzy¹,

Khalifa²

2016

Rheumatology (Sunnyvale)

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Background: Systemic Lupus Erythematous (SLE) is a prototype autoimmune disease of multifactorial origin mainly assigned to defects in the adaptive immune system. However, evidences supported the crucial role of the innate immune system in its pathogenesis. Toll-like receptors (TLRs) have been proposed as important pathways in disease development. This relatively new idea holds promise for new therapeutic strategies. The aim of this work is to measure surface expression of TLR2 and TLR4 on CD14+ monocytes in SLE patients and compare it with healthy controls, also to find out their relation with disease activity and damage. Subjects and methods: The current study was carried out on Forty Egyptian female SLE patients and 20 matched control subjects. Disease activity was assessed by the SLE disease activity index (SLEDAI) and damage assessed by the Systemic Lupus International Collaborating Clinics (SLICC) index. Expression of TLR2 and 4 on CD14+ monocytes was studied using flow cytometry. Results: The age of the patients ranged between 16-56 years with a mean ± SD of 31.6 ± 9.2 years. Significant increase of TLR2 surface expression and a significant decrease of TLR4 surface expression on CD14+ monocytes in SLE patients compared to the control group (p=0.006, 0.004, respectively) were observed. No statistically significant associations were detected with both activity and damage indices. Conclusion: This study suggests that TLR2 and 4 plays a role in the pathogenesis of SLE but have no impact on disease activity.

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Serum soluble toll‐like receptor 2: a novel biomarker for systemic lupus erythematosus disease activity and lupus‐related cardiovascular dysfunction

Abstract: Serum sTLR2 can attenuate disease activity and negatively impact left ventricular diastolic dysfunction and hypercholersterelemia in SLE patients. Statins, corticosteroids and chloroquine increase sTLR2 levels.

Cited by 26 publications

References 28 publications

The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker

The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker

Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage

Expression of TLR2 and TLR4 on CD14 Monocytes in Female SLE Patients E

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