Longitudinal analysis of Th1 (TNF-'alpha', IFN-'gamma', IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines in systemic lupus erythematosus: association with clinical and laboratory manifestations

Author(s)

Mariana Postal

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2016-05-02

Examining board members

Simone Appenzeller; Eduardo Ferreira Borba Neto; Alexandre Wagner Silva de Souza; Manoel Barros Bértolo; Ibsen Bellini Coimbra

• Advisor: Simone Appenzeller

Abstract

The aim of this study was to evaluate, during the period of two years, the sera levels of Th1 cytokines and Th2 in SLE patients and healthy controls, associating these cytokines with disease activity and the different clinical and laboratory manifestations presented by SLE patients, and also, to assess whether there was a variation in the sera of Th1 and Th2 cytokines levels and if they could be considered potential biomarkers. It was an open, longitudinal study with a control group. Consecutive SLE patients followed at the Rheumatology Unit (Hospital de Clínicas/UNICAMP) were recruited. Clinical, laboratory and medication were assessed. Disease activity was determined by [SLE Disease Activity Index (SLEDAI)] and the cumulative damage by [Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)]. Sera cytokines levels were performed by Enzyme Linked Immunosorbent Assay (ELISA). Two hundred and eighteen (210 women) SLE patients, with a mean age of 42.62 years [standard deviation (SD) ±11.98 years] were included. The control group, with similar age and sex distributions consisted of 46 (40 women) healthy volunteers with a mean age of 40.04±13.54. It was observed that IL-6 remained significantly increased in SLE patients compared to healthy controls over time. In the paired analyses, significant fluctuation in IFN-'gamma' (p=0.026), IL-12 (p<0.001), IL-4 (p=0.001) and IL-10 (p<0.001) levels were observed. There were no significant fluctuation in the sera TNF-? and IL-6 levels. It was observed that sera IL-10 levels were associated and correlated with disease activity, at follow up. INF-?, IL-4 and IL-10 were associated with NP manifestations in SLE patients. A significant difference was observed in the progressive loss of brain volume (p=0.028) and corpus callosum volume (p<0.001) of SLE patients compared to healthy controls. There was an association between IL-12 and progressive brain atrophy (p=0.008) and a direct correlation between sera IL-12 levels and percentage loss of brain volume (rs=0.3; p=0.015) was observed. No association between progressive brain atrophy and other cytokines or clinical and laboratory manifestations were observed. To sum up, there is a significant fluctuation in sera IFN-'gamma', IL-12, IL-4 and IL-10 levels in SLE patients. IL-10 may be considered a biomarker for disease activity and nephritis in SLE. IFN-'gamma', IL-4 and IL-10 can identify patients with CNS involvement. IL-12 may be considered a biomarker for brain damage in SLE (AU)

• FAPESP's process: 11/03788-2 - Longitudinal evaluation of interleukins 4, 6, 10 and 12, interferon gamma and tumor necrosis factor alpha and laboratory and clinical associations in systemic lupus erythematosus
• Grantee: Mariana Postal Zink de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate