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Caspase-1 is active since the early phase of rheumatoid arthritis
  1. Rita Cascão1,
  2. Joaquim Polido-Pereira1,2,
  3. Helena Canhão1,2,
  4. Ana Maria Rodrigues1,2,
  5. Márcio Navalho1,3,
  6. Helena Raquel1,
  7. Ana Filipa Mourão1,4,
  8. Catarina Resende2,
  9. José Alberto Pereira da Silva2,
  10. João Eurico Fonseca1,2,
  11. Luis Ferreira Moita1
  1. 1Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
  2. 2Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon, Portugal
  3. 3Radiology Department, Hospital da Luz, Lisbon, Portugal
  4. 4Rheumatology Department, Centro Hospitalar de Lisboa Ocidental, EPE, Hospital Egas Moniz, Lisbon, Portugal

Abstract

Background We have previously reported an increase in interleukin (IL)-1β levels in very recent onset arthritis. Therefore, molecular mechanisms that regulate IL-1β secretion, such as caspase-1 activation, might play a relevant role in arthritis onset and progression.

Objectives Our main goal was to evaluate caspase-1 state of activation in early polyarthritis and established rheumatoid arthritis (RA) patients.

Materials and methods Blood samples were collected from 12 untreated early polyarthritis patients, 12 established RA patients and 10 healthy controls. Caspase-1 activity was assessed using a carboxyfluorescein FLICA detection kit.

Results We found that both early polyarthritis and established RA patients have higher active caspase-1 levels. Surprisingly, caspase-1 activation levels in patient cells remain unchanged when cells were stimulated with Escherichia coli and ATP, whereas in control cells caspase-1 levels increased after stimulation. We observed no significant differences when comparing early polyarthritis with established RA samples. However, in RA patients with higher disease activity the proportion of active caspase-1 is higher.

Conclusions Our results suggest that leucocytes in both early polyarthritis and established RA patients have high baseline levels of activated caspase-1, which cannot be significantly increased after stimulation. Altogether, our data supports the hypothesis that caspase-1 is activated in early arthritis.

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