The thymus is widely recognized as an immunological niche where autoimmunity against the
acetylcholine receptor (AChR) develops in
myasthenia gravis (MG) patients, who mostly present
thymic hyperplasia and
thymoma.
Thymoma-associated MG is frequently characterized by
autoantibodies to the muscular
ryanodine receptor 1 (
RYR1) and
titin (TTN), along with anti-AChR
antibodies. By real-time PCR, we analyzed muscle-CHRNA1,
RYR1, and TTN-and muscle-like-NEFM,
RYR3 and HSP60-autoantigen gene expression in MG thymuses with
hyperplasia and
thymoma, normal thymuses and non-MG
thymomas, to check for molecular changes potentially leading to an altered antigen presentation and autoreactivity. We found that CHRNA1 (AChR-α subunit) and AIRE (autoimmune regulator) genes were expressed at lower levels in hyperplastic and
thymoma MG compared to the control thymuses, and that the
RYR1 and TTN levels were decreased in MG versus the non-MG
thymomas. Genes encoding
autoantigens that share
epitopes with AChR-α (NEFM and HSP60),
RYR1 (neuronal
RYR3), and TTN (NEFM) were up-regulated in
thymomas versus hyperplastic and control thymuses, with distinct molecular patterns across the
thymoma histotypes that could be relevant for autoimmunity development. Our findings support the idea that altered muscle
autoantigen expression, related with hyperplastic and neoplastic changes, may favor autosensitization in the MG thymus, and that molecular mimicry involving
tumor-related muscle-like
proteins may be a mechanism that makes
thymoma prone to developing MG.