Systemic sclerosis in a patient with muscle dystrophy.
Sara Moutinho-PereiraEurico Morais-de-SáHelena GreenfieldP Ricardo PereiraPublished in: BMJ case reports (2022)
Systemic sclerosis is an autoimmune disease that can result in lung fibrosis, and is strongly associated with the presence of serum anti-topoisomerase-I autoantibodies. A young man with genetic muscular dystrophy caused by titin-cap/telethonin ( TCAP ) gene mutation, developed a severe restrictive lung disease due to a fibrosing interstitial pneumonia secondary to systemic sclerosis with positive anti-topoisomerase-I antibodies. Using amino acid sequence alignment and protein structure modelling, we found that mutant telethonin exposes an amino acid sequence with significant homology to an immunodominant site of topoisomerase-I. Abnormal telethonin results in a loss of integrity of the sarcomere structure, which might result in rhabdomyolysis and abnormal protein exposure to the immune system. Our preliminary analysis suggests a possible role for mutant sarcomere protein telethonin as an immunogenic target recognised by anti-topoisomerase-I antibodies, which could explain the development of systemic sclerosis in this particular patient.
Keyphrases
- systemic sclerosis
- amino acid
- interstitial lung disease
- case report
- early onset
- protein protein
- acute kidney injury
- binding protein
- multiple sclerosis
- genome wide
- intensive care unit
- small molecule
- gene expression
- dna methylation
- duchenne muscular dystrophy
- extracorporeal membrane oxygenation
- community acquired pneumonia