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THU0239 Serum HMGB1 and TLR4 levels as novel biological markers for the activities of neuropsychiatric systemic lupus erythematosus
  1. Q Huang1,
  2. C Yuan2,
  3. H Ren1,
  4. M Yang1
  1. 1Department of Rheumatology
  2. 2Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Abstract

Background Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe complication of SLE, including a variety of neurological and psychiatric features. Previous studies have demonstrated the close relationship between NPSLE and inflammation. HMGB1-TLR4 signaling pathway is the up-stream pathway of NF-κB, which could upregulate the expression of various cytokines and other inflammatory mediators.

Objectives The objective of the study was to explore the potential mechanism of HMGB1-TLR4 axis in SLE.

Methods The study population consisted of 107 SLE patients and 43 age- and sex-matched healthy controls. 73 SLE patients had active disease. 36 of these had NPSLE. The serum anti-NR2A antibodies levels were measured by ELISA. Clinical and serological parameters were assessed according to routine procedures. HMGB1 and TLR4 levels were measured by ELISA.Statistical analyses were performed by using the chi-square test and the t-test.

Results CNS manifestations accounted for 94% (34/36 patients), while involvement of the PNS was 6% (2/36patients). The majority of the manifestations were Seizure disorders (n=17; 47.2%),Headache (n=12; 33.3%), Cognitive dysfunction (n=10; 27.8%), Psychoses (n=8; 22.2%).Within the group of active patients those with NP manifestations had higher HMGB1 levels (0.451 (0.292 to 0.583)) compared to active patients with non-NP manifestations (0.356 (0.098 to 0.436)). In patients with NP (0.429 (0.313 to 0.526)) and non-NP (0.375 (0.196 to 0.478)) manifestations during active periods of the disease, TLR4 levels significant increased in comparison to the controls. TLR4 levels were significantly higher in active patients (0.401 (0.196 to 0.526)) compared to quiescent patients. There was a significant positive correlation between levels of HMGB1 and TLR4 in the total patients group (P<0.0001, r=0.939).We observed a correlation between HMGB1 levels and SLEDAI (P<0.0001, r=0.804). Also, TLR4 levels showed a significant correlation with SLEDAI (P<0.0001, r=0.809). HMGB1 levels correlated with anti-dsDNA levels (P<0.0001, r=0.558). Similarly, TLR4 showed a correlation with anti-dsDNA levels (P<0.0001, r=0.522).We observed a negative correlation in the total SLE group between C3, C4 and HMGB1 levels (P<0.0001, r=-0.545 and P<0.0001, r=-0.270 respective. Also, TLR4 showed a significant negative correlation with C3 and C4 (P<0.0001, r=-0.559 and P<0.0001, r=-0.285 respectively).

Conclusions Our data suggest that HMGB1-TLR4 axis plays an important role in the pathogenesis of SLE as well as NPSLE.

Acknowledgements This work was supported by The President Foundation of Nanfang Hospital, Southern Medical University (NO. 2014C009, NO.2015C021).

Disclosure of Interest None declared

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