1. B-CELL SUBSETS DIFFERENCES IN INFLAMMATORY RHEUMATIC DISEASES
João Lagoas Gomes, Dario Ligeiro, Alice Lima, Alexandre Sepriano, Cristiana Teixeira, Carina Lopes, Tiago Costa, Sofia Ramiro, Margarida Mateus, Maria Manuela Costa, Jaime C. Branco, Fernando Pimentel-Santos 1

2. B-cell subsets in inflammatory rheumatic diseases
Background
Objectives
Material and Methods
Results
Conclusions
Future Perspectives

3. B-cell subsets in inflammatory rheumatic diseases
Background
Spondyloarthritis (SpA), Rheumatoid arthritis (RA), Systemic Lupus erithematosus (SLE) are the most common and serious inflammatory arthritis.
Risk
Joint destruction
Functional impairment
 morbidity
Early retirement
 QoL
 mortality
SpA RA
SLE

4. B-cell subsets in inflammatory rheumatic diseases
Background
Window of Opportunity
A period, early in the course of the disease when:
the disease process can be altered or maybe even reversed
a complete return to normality – REMISSION- is possible
sustainability
12 weeks

5. B-cell subsets in inflammatory rheumatic diseases
Background
Early Diagnosis
T2T
Better Outcomes
Effective Therapies
A period early in the course of the disease when:
the disease process can be altered or maybe even reversed
a complete return to normality – REMISSION
sustainability
Remission

6. B-cell subsets in inflammatory rheumatic diseases
Background

7. B-cell subsets in inflammatory rheumatic diseases
Background
Relevance of Biomarkers for:
Early Diagnosis
Prognosis
Therapy selection
New Therapeutic Targets

8. B-cell subsets in inflammatory rheumatic diseases
Background
B cells in SpA
No auto-antibodies;
Not relevant for physiopathology;
Immune regulatory genes suggesting B-cell dysfunction1;
Clinical trials have shown some efficacy of B-cell depletion in ankylosing spondylitis2.  

9. B-cell subsets in inflammatory rheumatic diseases
Objectives
To assess and compare the subsets of peripheral B-cell compartment in AS with HC, RA and SLE.
SpA RA
LES HC

10. B-cell subsets in inflammatory rheumatic diseases
Material and Methods
Inclusion Criteria
Definitive Diagnosis of SpA, RA and SLE according to respective classification criteria;
Pts, 18 < Age (years) <65;
Capacity for given an informed consent.

11. B-cell subsets in inflammatory rheumatic diseases
Material and Methods
Exclusion Criteria
History of any concomitant inflammatory rheumatic disease
Any active or recurrent viral infection that, based on the Investigator's clinical assessment, makes the subject an unsuitable candidate for the study;
Infection(s) requiring treatment with parenteral anti-infectives within 30 days, or oral anti-infectives within 14 days prior the study inclusion;
History of any malignancy;
Receipt of any live vaccine within 4 weeks prior to the study inclusion;
Female who is pregnant or breastfeeding;
Prior exposure to any bDMARD(s)

12. B-cell subsets in inflammatory rheumatic diseases
Material and Methods
Sociodemographic and clinical variables
Peripheral Blood samples:
Inflammatory markers (ESR and CRP);
Immunoglobulin serum levels;
Flow cytometry: B-cell immature transitional stages and mature subsets.

13. B-cell subsets in inflammatory rheumatic diseases
Material and Methods
CD20+CD5+ compartement:
CD27-IgD+ - immature transitional cells
CD24+++CD T1
CD24++CD T2
CD24lowCD38+ - T3/pré-naive
CD27+IgD+ – B1a like cells?
CD20+CD5- compartement (mature):
CD27-IgD+ - naive
CD27+IgD+ - non-switched memory (+ MZ like)
CD27+IgD- - memory switched
CD27-IgD- - double negative

14. B-cell subsets in inflammatory rheumatic diseases
Results
60 pts : 12 HC
SpA (n=22)
RA (n=20)
SLE (n=18)
Low levels of inflammation (ESR, CRP)

15. B-cell subsets in inflammatory rheumatic diseases
Results

16. B-cell subsets in inflammatory rheumatic diseases
Results
No differences between groups.
Immunoglobulins
Normal range

17. B-cell subsets in inflammatory rheumatic diseases
Results
The immature transitional compartment:
SpA pts, N range
Not in the RA and SLE groups.

18. B-cell subsets in inflammatory rheumatic diseases
Results
Mature naïve cells, in:
RA and SLE, decreased
AS, normal range

19. B-cell subsets in inflammatory rheumatic diseases
Conclusions
Severe dysfunction in the homeostasis of the B-cell compartment in RA and in particular SLE pts ( immature and mature B-cell compartments);
SpA pts are not affected.

20. B-cell subsets in inflammatory rheumatic diseases
Future Perspectives
Evaluation of immunoglobin heavy chain (IGH) diversity repertoire by spectratyping
Functional studies appear to be necessary in order to identify differences in key mechanisms of B cell development and differentiation that may play a role in the aetiology and progression of IRD
Pathophysiological mechanisms involving B-cells clearly differentiate AS from RA and SLE.

21. B-cell subsets in inflammatory rheumatic diseases

22. B-cell subsets in inflammatory rheumatic diseases
Aknowledgments
Rheumatic Disease, Myo and Pain Lab, CEDOC
Jaime C. Branco
Alexandre Sepriano
Carina Lopes
Fernando Pimentel-Santos
João Lagoas Gomes
Tiago Costa
Instituto Português do Sangue e Transplantação
Dário Ligeiro
Alice Lima
Cristiana Teixeira
CHLO, Hospital de Egas Moniz
Jaime C. Branco
Alexandre Sepriano
Carina Lopes
Fernando Pimentel-Santos
João Lagoas Gomes
Maria Manuela Costa
Margarida Mateus
Tiago Costa
Leiden University Medical Center, Netherlands
Alexandre Sepriano
Sofia Ramiro