Autoantibodies targeting telomere-associated proteins in systemic sclerosis

Area of Science:

• Immunology
• Genetics
• Pulmonology

Background:

• Systemic sclerosis (SSc) is an autoimmune fibrotic disease impacting multiple organs, notably the lungs.
• A subset of SSc patients with lung involvement shows shortened telomeres in lymphocytes, but the underlying mechanisms remain unclear.

Purpose of the Study:

• To investigate autoantibodies targeting telomerase and shelterin proteins in SSc patients.
• To determine the association between TERF1 autoantibodies, telomere length, and clinical features, particularly lung disease.

Main Methods:

• Sera from SSc patients were screened for autoantibodies against telomerase and shelterin proteins using immunoprecipitation and ELISA.
• Telomere length in peripheral leukocytes was measured using qPCR and Flow-FISH.
• Clinical associations of identified autoantibodies were explored.

Main Results:

• Autoantibodies targeting telomerase and shelterin proteins were identified in SSc patients, rarely found in controls.
• TERF1 autoantibodies were present in 9.0% of SSc patients and associated with severe lung disease and short lymphocyte telomeres.
• TERF1 autoantibodies were also found in 7.2% of idiopathic pulmonary fibrosis (IPF) patients.

Conclusions:

• Autoantibodies targeting telomere-associated proteins in SSc are linked to short telomere length and lung disease.
• The presence of these autoantibodies in both SSc and IPF suggests a role for telomere dysfunction in the pathogenesis of these fibrotic diseases.