SERHA

Patterns of cellular and molecular senescence in rheumatoid arthritis and study of its response to an autologous serum enriched in cytokines.

Welcome to SERHA

The main objective of the SERHA project is to study the influence of aging in patients with rheumatoid arthritis (AR) and his influence on the pathophysiology of the disease converted to improve the healthy lives of the aging population.

In addition, we intend to develop "in vitro" models to reproduce the joint pathophysiology of these patients to test a new autologous therapy, based on the patients' plasma, enriched in cytokines (cytokine-rich autologous serum, SARC). We will develop a joint-on-a-chip model to study the cellular interactions and pathophysiology of rheumatoid arthritis.

With this aim, a multidisciplinary group of basic and clinical researchers from the I3PT, QREM and Leitat has been set up, coordinated by the I3PT, to work together and advance quickly with the proposed objectives. The SERHA project is part of industrial research, with the collaboration between a clinical research center (I3PT), a company (QREM), an applied research center (Leitat).

Thanks to the interdisciplinarity of the partners involved, a combination of disciplines at a methodological, conceptual and theoretical level is proposed to respond to the challenges identified in the theme "geroscience and gerotherapeutics; molecular basis of healthy aging and prevention of aging diseases" of the call "R+D+i Projects in Líneas Estratégicas del Ministerio de Ciencia e Innovación 2022", and will allow the development of innovative advanced therapies and their transfer to the patients in the near future.

Financing

Project SERhas been funded by MCIN/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/ PRTR

Development of SERHA

Targets

SO1. To analyze senescence biomarkers in peripheral blood mononuclear cells and synovial fluid of patients with elderly-onset RA (EORA) and young-onset RA (YORA). These biomarkers will include biomarkers of senescence (CD28), telomere length, cytokine expression among others.

SO2. Develop "in vitro" models of EORA, as well as cell co-culture models to study cellular interactions, involved in pathophysiological pathways in EORA diseases.

SO3. Characterization of SARCs, to analyze the mechanisms of action of this new therapeutic product and its effects on in vitro models of RA.

SO4. Development of the join on a chip model, to obtain an "in vitro" physiological model. This model could serve to evaluate the therapeutic effects of SARCs

 

Patient cohort

Inclusion criteria:
Patients who sign informed consent, meet the ACR/EULAR 2010 rheumatoid arthritis (RA) classification criteria and/or the ACR 1987 RA classification criteria will be included. Patients will be stratified according to age and 'clinical activity.

Definition of stratification by age (according to age of RA onset):

– If ≥60 years: elderly-onset rheumatoid arthritis (EORA)

– If <60 years: young onset rheumatoid arthritis (YORA)

Definition of inflammatory activity:

– Active inflammatory activity: patients with DAS28PCR ≥2,6, with a duration of less than one year from the onset of symptoms and who have not taken doses higher than 5 mg of prednisone or disease-modifying antirheumatic drugs (DMARDs).

– Clinical remission: DAS28PCR <2,6, ideally in those patients in whom we have induced remission within the observation time of the study.

Definition of seropositivity:

-Seropositive: ACPA positivity proven by ELISA or chemiluminescence test (CCP2) and/or rheumatoid factor positivity (ELISA, nephelometry or chemiluminescence)

-Seronegative: those patients with ACPA negativity proven by ELISA or chemiluminescence test (CCP2) and rheumatoid factor negativity (ELISA, nephelometry or chemiluminescence)

As a scheme of patients to be recruited:

– 15 FR and/or ACPA EORA seropositive in an inflammatory state
– 15 FR and/or ACPA EORA seropositive in remission
– 15 FR and/or ACPA seronegative EORA in an inflammatory state
– 15 FR and/or ACPA seronegative EORA in remission
– 15 YORA in an inflammatory state
– 15 YORA in remission
– 15 patients with osteoarthritis
– 15 age-matched healthy controls with the 15 EORA
– 15 age-matched healthy controls with the 15 YORA

Control cohort

As a control group without arthritis, the patients of the osteoarthritis cohort of the HU will be recruited the Parc Taulí, while the healthy age (≥60 years) and young (<60 years) controls of the Blood and Tissue Bank (BST) and HU Parc Taulí.

The samples to collect

At the Parc Taulí Hospital, blood and synovial fluid samples will be collected from patients with EORA (n=60), YORA (n=30), osteoarthritis (n=15), to obtain plasma, PBMC, SARC and LS and LSMC.

Age-matched healthy controls will be obtained from blood donors (BST) and HUParc Taulí to obtain plasma, PBMC and SARC.

Participating centers

  • Parc Taulí Research and Innovation Institute (Sabadell)
  • Qrem
  • Leitat
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