Autoantibodies to the TNF-α translational regulators TIA-1 and TIAR occur frequently in sera of patients with SLE and scleroderma

Objective

The two closely related RNA binding proteins TIA-1 and TIAR are involved in post-transcriptional regulation of TNF expression by acting as translational silencers via association with the TNF mRNA. Given that TNF is upregulated in many inflammatory and autoimmune conditions it was the aim of this study to investigate the possible occurrence of autoantibodies (aab) against TIA-1 and TIAR in patients with rheumatic diseases.

Methods

Recombinant proteins were employed in immunoblotting studies involving sera of 40 patients with SLE and 20 sera each of patients with systemic sclerosis (SCL), poly/dermatomyositis (PM/DM), Sjögren's syndrome (SS), rheumatoid arthritis (RA), reactive arthritis (REA) as well as sera of 20 healthy controls (HC).

Results

IgG aab against TIA-1 and/or TIAR were frequently detected in sera of patients with SLE or SCL: thus, 67% of SLE sera (anti-TIA1: 52%, anti-TIAR: 47%) and 50% of the SCL sera (anti-TIA1: 40%, anti-TIAR: 40%) contained either of the two aab. These aab were detected at lower frequency also in sera of patients with PM/DM (30%), REA (25%), SS (15%) and RA (10%). However, only PM/DM patients differed significantly (P < 0.05) from healthy controls (5%). Due to the close structural homology between the two proteins the majority of sera were reactive with both of them suggesting a high degree of crossreactivity. Nevertheless, some sera contained auto-antibodies directed specifically to only one of two antigens.

Conclusion

Autoantibodies to TIA-1 and TIAR occurred frequently in patients with SLE and SCL but, interestingly, were rarely detectable in patients with RA. Thus, these data suggest that in susceptible individuals systemic upregulation of TNF may lead to autoimmune reactions against proteins associated with the TNF mRNA.