Detailed immune cell profiling of paediatric patient with limb girdle muscular dystrophy R3.

Muscular dystrophies are associated with inflammation and necrotic myofibres where muscle is replaced with adipocytes/fibrosis. Glucocorticoids provide clinical improvement in reducing immune markers for some muscular dystrophies however, knowledge of the immune cells involved is limited. Here we present a childhood onset case of Limb Girdle Muscular Dystrophy (LGMD) with two pathogenic variants for SGCA gene. Muscle biopsy (eight-years) was consistent with sarcoglycanopathy, revealing necrotic myofibres, inflammatory infiltrate (CD45+) positive for monocyte/macrophages (CD45+CD68+) and evidence of adipocytes/fibrosis. Blood was collected (eleven-years) to perform detailed immune cell profiling identifying >60 subtypes of Innate, T and B cells (compared to age-sex matched controls). We found alterations in natural killer (NK) cells (CD3-CD19-CD20-CD14-CD56dim/bright), monocytes (CD3-CD19-CD20-CD14+/-HLADR+CD16+/-), dendritic cells (DCs) (CD3-CD19-CD20-CD14-CD16-HLADR+), T lymphocytes (CD3+CD4+/-CD8+/-), unconventional T lymphocytes (CD3+γδTCR+ and CD3+Vα7.2hiCD161hi and CD3+TCRVα24Jα18) and B lymphocytes (CD3-CD19+CD20+). This is the first study to perform detailed immune cell profiling of a LGMD patient. The data presented is a singular result but highlights the need to build cohort studies for a more in-depth investigation of the LGMDR3 immune profile and discovery of immune targeted therapies.