Ultrasound in Rheumatoid Arthritis: Association Between the Polymorphism -308 A/G of Tumor Necrosis Factor and the Severity of Bone Erosive Damage

Introduction

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease affecting primarily the synovial joints, involving approximately .5–1% of the population. The genetic background is responsible for part of the disease susceptibility and phenotype as demonstrated by twin and family studies. The Human Leukocyte Antigen (HLA)-DRB1 Shared Epitope (SE) locus has been found strongly associated with the disease, accounting for approximately one-third of the genetic component of RA susceptibility.1 Thus, other non-HLA genes may have a role in the disease development and researches focused on genes encoding for cytokines in key pathogenic pathways.

Abstract

INTRODUCTION

Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive bone damage. The tumor necrosis factor (TNF) -308A/G polymorphism was associated with erosive radiographic progression. Musculoskeletal ultrasound (US) was found superior to radiography to identify bone erosions within small joints (metacarpophalangeal [MCP], hand proximal interphalangeal [PIP], metatarsophalangeal [MTP]) in patients affected with RA.

OBJECTIVES

To evaluate the association of TNF -308G/A with bone erosions assessed with an ultrasound.

STUDY DESIGN

Fifty-two patients affected by RA criteria were genotyped for TNF -308G/A. Disease activity was measured with the disease activity score in 28-joints (DAS28) and the clinical response was evaluated according to the European League Against Rheumatism (EULAR) response criteria. Rheumatoid factor (RF) and anticitrullinated protein/peptides antibodies (ACPA) were detected. The analysis of the TNF -308G/A polymorphism was made by polymerase chain reaction amplification. An ultrasound was performed to assess bone surfaces of metacarpophalengeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) joints by multiplanar scans. According to the number of erosions per joint, a semiquantitative score (range 0–3) was applied. A score in each anatomical district was calculated obtaining MCP-total erosion score (TES), PIP-TES, and MTP-TES, ranging from 0 to 30, and a global TES-patient from the sum of these scores (range 0–90).

RESULTS

TNF -308GG genotype was present in 43 patients while TNF -308AG/AA was present in 9 patients. No significant differences within the two groups were observed for mean age (56±13.8 vs 56.8±16.1 years), disease duration (141.6±117.6 vs 140.4±72.3 months), rheumatoid factor (33/76.7 vs 8/88.8 [N/%]), ACPA (38/88.4 vs 8/88.8 [N/%]), ESR (32.4±26.9 vs 29.4±19.9 mm/h), DAS28 (5.5±1.0 vs 4.6±1.3), HAQ (1.5±.9 vs 1.1±.7). A significant association was found between TNF -308AG/AA genotypes and higher TES patient (28.5±23.7 vs 38.1±17.1 [P<.05]), MCP TES (11.2±8.2 vs 18±8.4 [P=.027]), MTP TES (8.2±8 vs 11.2±6 [P<.05]), and no differences for PIP TES (8.7±8.9 vs 8.9±6.2).

CONCLUSION

This study showed an association between the TNF -308 A allele, linked to higher TNF expression, and bone erosive damage evaluated by ultrasound in patients with RA. This preliminary result confirms previous radiographic studies.

Keywords

Rheumatoid arthritis, tumor necrosis factor, musculoskeletal ultrasound, polymorphism, erosion