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-CD56^dim/^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⁺Vα7.2^hiCD161^hi 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.