Comparisson of adult and childhood-onset systemic lupus erythematosus: clinical, laboratorial profile and cytokines IL-6, IL-10 and IL-12

Author(s)

Karina de Oliveira Peliçari

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2017-02-24

Examining board members

Simone Appenzeller; Evandro Mendes Klumb; Luíz Carlos Latorre; Manoel Barros Bértolo; Ibsen Bellini Coimbra

• Advisor: Simone Appenzeller; Lilian Tereza Lavras Costallat

Abstract

Objective: To compare longitudinally clinical and laboratory manifestations, treatment and cytokines in childhood (cSLE) and adult-onset (aSLE) systemic lupus erythematosus. Methods: We included 1261 consecutive patients with closed diagnosis of SLE that were followed at the Adult and Pediatric Rheumatology Unit of the State University of Campinas. Clinical, laboratory and treatment data were obtained from 1974 to 2016 through a special database. The data were evaluated in two moments, at onset (6 months after the diagnosis was closed) and follow-up (after the first 6 months after diagnosis) of the disease. Patients were divided into two groups according to the age of disease onset: cSLE (onset of disease ?18 years) and aSLE (onset of disease> 18 years). 336 (27%) patients were cSLE [mean disease duration 12.1 ± 8.1 years] and 927 (73%) aSLE [mean disease duration 19.4 ± 10.7]. Subsequently, we separated 130 patients [63 cSLE (mean disease duration 7.3 ± 4.2 years) and 67 aSLE (mean disease duration 7.7 ± 3.1)], matched by disease duration, and included 40 controls with similar gender to patients for cytokine analysis. We performed 4 blood samples at 4 different times (TI, TII, TIII and TIV) in a period of 2 years, in addition to the collections, clinical manifestations, laboratorial, treatment, disease activity (SLEDAI), anxiety (BAI) and depression (BDI) symptoms were evaluated at all times. Cumulative damages (SDI) were assessed in the last time. Levels of Th1 (IL-12) and Th2 (IL-6 and IL-10) cytokines were measured by ELISA test and compared by non-parametric tests. It was considered significant when p?0.05. Results: At the onset and follow-up of the disease, cSLE patients had significantly more frequently malar rash [onset p=0.011 and follow-up p=0.019], oral ulcers [onset p=0.002 and follow-up p<0.001], migraine [onset p<0.001 and follow-up p<0.001], chorea [onset p=0.001 and follow-up p=0.001] and proteinuria [onset p=0.006 and follow-up p=0.003] than aSLE patients. aSLE patients had significantly more arthritis [onset p<0.001 and follow-up p<0.001] and Raynaud's phenomenon [onset p=0.001 and follow-up p=0.049]. Anti-dsDNA was significantly more frequent in cSLE patients (p<0.001) and anti-SSA was more frequent in aSLE patients (p=0.020). cSLE patients took more doses of prednisone (p<0,001), azathioprine (p=0.023), cyclophosphamide (p<0.001), and mycophenolate (p<0.001). During follow-up, significantly more SLE patients died (p=0.020). In relation to cytokines, IL-6 was higher in aSLE patients when compared to healthy controls (TI p=0.013, TII p=0.015, TIII p=0.004, TIV p=0.634) and IL-12 was significantly higher in cSLE patients when compared to healthy controls (TI p=0.04, TII p<0.001, TIII p=0.015, TIV p=0.021). However, there was no significant difference at all times in any cytokine between cSLE and aSLE patients. In aSLE patients, IL-6 was associated with migraine (p=0.006), arthritis (p=0.044) and nephritis (p = 0.012), IL-10 was associated with nephritis (p=0.043), hypocomplementemia (p=0.001) and disease activity (p=0.001) and IL-12 was associated with alopecia (p=0.025) and leukopenia (p=0.044). In cSLE patients, IL-6 was associated with arthritis (p=0.022) and malar rash (p=0.012). Conclusion: cSLE patients have a higher frequency of mucocutaneous and neuropsychiatric manifestations, whereas aSLE patients have a higher frequency of arthritis. cSLE and aSLE patients with long disease duration, present similar levels of cytokines. In aSLE patients, IL-6 was associated with migraine, arthritis and nephritis and in cSLE, IL-6 was associated with arthritis and malar rash. IL-10 was associated with nephritis, hypocomplementemia and disease activity, and IL-12 was associated with alopecia and leucopenia in LESa (AU)

• FAPESP's process: 12/21071-0 - Longitudinal study of interleukin 6, 10,12 and 17 and associations with clinical and laboratory findings in patients with systemic lupus erythematosus
• Grantee: Karina de Oliveira Peliçari
• Support Opportunities: Scholarships in Brazil - Doctorate