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Abstract Number: 1622

Th1 and Th2 Cytokines Are Associated with Cerebral Atrophy in Systemic Lupus Erythematosus

Mariana Postal1, Aline T. Lapa1, Karina de Oliveira Peliçari2, Nailu A. Sinicato1, Fernando Augusto Peres1, Wesley Geraldo Ferreira2, Roberto Marini2, Lilian Costallat3, Fernando Cendes4 and Simone Appenzeller5, 1Medicine, State University of Campinas, Campinas, Brazil, 2State University of Campinas, Campinas, Brazil, 3Medicine, State University of Campinas, Campinas, United Kingdom, 4Neurology, State University of Campinas, Campinas, Brazil, 5Medicine, Faculty of Medical Science, State University of Campinas Unicamp, São Paulo, Brazil

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: cytokines, magnetic resonance imaging (MRI) and systemic lupus erythematosus (SLE)

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Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Autoimmune Disease Transition, Disease Subsets and Prediction of Flares, Cytokines and Autoantibodies

Session Type: Abstract Submissions (ACR)

Background/Purpose

Cerebral atrophy has been described to occur in systemic lupus erythematosus (SLE) with variable frequency. The pathophysiology of central nervous system (CNS) involvement in SLE remains unclear. The proposed mechanisms that are likely due to the assault of several autoimmune system changes include circulating immune complexes, corticosteroid use, autoantibodies, and cytokine release. The aim of this study was to determine the prevalence of cerebral atrophy and to elucidate the possible role of sera Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-4, 5,6 and 10) cytokines levels in SLE.

Methods

Consecutive SLE patients followed at the rheumatology unit of the State University of Campinas were enrolled in this study. The control group was consisted by age and sex matched healthy individuals. A complete clinical, laboratory and neurological evaluation was performed in all subjects. Neurological manifestations were analyzed according to the ACR classification criteria. Mood and anxiety disorders were determined through Becks Depression and Becks Anxiety Inventory. 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. Magnetic resonance imaging (MRI) scans were performed in a 3T Phillips®scanner using a standardized protocol. Sagittal T1 weighted images were used for semiautomatic volumetric measurements. Volumes smaller 2 standard deviation from the means of controls were considered abnormal. Total dose of corticosteroids and other immunosuppressant medications used since the onset of disease were calculated by data obtained by careful review of the medical charts. Sera samples were obtained from all participants in the absence of infections. Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-4, 5,6 and 10) cytokines sera levels were measuredby ELISA using commercial kits.  Data were compared by non-parametric tests.

Results

We included 146 SLE patients (138 women; mean age of 26.60±13.42 years; range 9-67) and 91 (86women; mean age of 27.82± 15.23 years; range 5-80) age and sex matched healthy controls. The median and range of cerebral volume in SLE patients was 1064.16cm3(range 831.1-1449.24) cm3, compared to healthy volunteers 1134.46 (range 880.01-1417.59) cm3(p<0.001). Cerebral atrophy was identified in 20 (13.69%) SLE patients and in none of controls (p<0.001). Significantly increased Th1 [IL-12 (p<0.001), IFN-γ (p<0.001), TNF-α (p<0.001)] and Th2 [IL-4 (p=0.002), IL-5 (p<0.001), IL-6 (p=0.001) and IL-10 (p<0.001)] levels were observed in SLE patients compared to controls. We observed an association between cerebral atrophy and IL-12 (p=0.044), IFN-γ (p=0.017) and IL-10 (p=0.003). We did not observe association between cerebral volume and corticosteroidsor any other clinical or laboratory manifestations. 

Conclusion

IL-12, IFN-γ and IL-10 were associated with cerebral atrophy in SLE, suggesting immunological basis for global atrophy in SLE. Cytokines have been highlighted as potential contributory factors to cerebral atrophy in SLE.


Disclosure:

M. Postal,
None;

A. T. Lapa,
None;

K. D. O. Peliçari,
None;

N. A. Sinicato,
None;

F. A. Peres,
None;

W. G. Ferreira,
None;

R. Marini,
None;

L. Costallat,
None;

F. Cendes,
None;

S. Appenzeller,
None.

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