This study examined whether HLA-G expression could predict disease progression in patients with early rheumatoid arthritis (ERA). The study found that ERA patients had significantly lower serum HLA-G levels compared to controls. However, disease-modifying antirheumatic drug (DMARD) therapy led to increased HLA-G expression and lower inflammatory cytokine levels over 12 months. Patients with initially lower HLA-G expression experienced a more severe disease course. The results suggest that DMARD therapy modifies HLA-G secretion and exerts its disease-modifying effects in ERA partly by suppressing the Th1 immune response.

1. HLA-G may predict the disease course in patients
with early Rheumatoid Arthritis
Presented By: Nima Taefehshokr
MSc Biomedical Immunology
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Human Immunology 74 (2013) 425-432

2. 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.
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3. 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.
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4. 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.
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5. BiologicalTherapeutics
Targets, Rationale, Status
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Indian J Dermatol Venereol Leprol | September-October 2009 | Vol 75 | Issue 5

6. 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.
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7. 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
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8. sHLA-G plasma levels
Figure.3 Increased levels of sHLA-G during 12 months therapy on the basis of DAS28 and
US-PD scores.

9. 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.
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10. 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

11. 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.
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12. 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.
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Thank you.