HLA-G may predict the disease course in patients

with early Rheumatoid Arthritis

Presented By: Nima Taefehshokr

MSc Biomedical Immunology

1

Human Immunology 74 (2013) 425-432

INTRODUCTION

• Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that is

characterized by synovitis leading to cartilage damage, bone erosion, joint

deformity and disability.

• Don’t forget the spinal cord.

• Both prevalence and incidence are 2-3 times

greater in women than in men.

• It affects approximately 1% population.

2

Key Factors

• Genetic: HLA-DR4 allels, PTPN22.

• Autoimmune: high titers of RF,

anti –CCP.

• Environmental: smoking, stress,

microorganisms.

• Endocrinologic: low levels of hormones from

the adrenal gland.

3

Pathogenesis of RA

• Intimal cell proliferation

• Inflammatory cell infiltration: T cells, B cells, macrophages and plasma cells.

• Production of cytokines and proteases.

• Increased vascularity.

• Self amplifying process.

4

Biological TherapeuticsTargets, Rationale, Status

5Indian J Dermatol Venereol Leprol | September-October 2009 | Vol 75 | Issue 5

Reliable biomarker for ERA disease status

o HLA-G antigens are expressed as membrane bound and soluble

isoforms (mHLA-G , sHLA-G).

o These antigens are characterized as anti-inflammatory and

immunoinhibitory functions which act as ligand for ILT2, ILT4,

KIR2DL4.

o It has been reported that serum HLA-G concentration is significantly

lower in ERA patients.

o But, after DMARD (Disease-modifying Antirheumatic Drugs) therapy

there was a consistent up-modulation of HLA-G and ILT2.

6

Materials and methods

In this experiment 23 patients suffering from Early Arthritis met the criteria

to undergo DMARD therapy and were followed for 1 year.

o HLA-G polymorphism typing

o sHLA-G ELISA

o Cytokine plasma levels

o Cytometric analysis of PBMC

7

sHLA-G plasma levels

Figure.3 Increased levels of sHLA-G during 12 months therapy on the basis of DAS28 and

US-PD scores.

Cytokine plasma levels

Figure.4 (a) IL-1beta, IL-6, TNF –alpha, IL-10 plasma levels in Control subjects (HC),

ERA patients (ERA) and OArth subjects (OArth) before the therapy.

(b) IL-1 beta, IL-6, TNF-alpha, IL-10 levels during the 12 months follow-up disease

treatment.

9

Membrane HLA-G and ILT2 analysis by flow cytometry

(a) Increased expression of HLA-G and ILT2. (b) unmodified and slight increase of HLA-G,

ILT2 respectively. 10

Summery

• Low sHLA-G and mHLA-G expression suffered a more severe disease.

• DMARD therapy is able to modify HLA-G secretion.

• This confirmed the anti-inflammatory effect of DMARD by cytokine

evaluation that exerted its disease modifying effect partly by suppressing

Th1.

11

References

Rizzo, R., Farina, I., Bortolotti, D., Galuppi, E., Rotola, A

.,Melchiorri, L., Ciancio, G., Di-Luca, D. & Govoni,M.

2013. HLA-G may predict the disease course in patients with

early rheumatoid arthritis. Human Immunology. 74, 425-432.

12

13

Thank you.