1971: Muscle Pathology in Patients with Primary Biliary Cholangitis

Jose Cesar Milisenda¹, Iago Pinal-Fernandez², Katherine Pak², Maria Casal-Dominguez³, Yaiza Duque-Jaimez⁴, Gloria Garrabou¹, Sandra Muñoz-Braceras⁵, Mariona Guitart-Manpel¹, Jose Jiram Torres-Ruiz⁵, Ester Tobias⁴, Maria Dolores Cano⁴, Iban Aldecoa⁴, Josep Maria Grau¹ and Andrew Mammen³, ¹Muscle Research Unit, Internal Medicine Service, Hospital Clinic, Barcelona, Spain, ²National Institutes of Health, Bethesda, MD, ³NIH, Bethesda, MD, ⁴Hospital Clínic de Barcelona, Barcelona, Spain, ⁵Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD

Background/Purpose: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that primarily affects middle-aged women. It is characterized by elevated serum alkaline phosphatase levels, the presence of antimitochondrial antibodies (AMAs), and cholangiopathy on liver pathology. Fatigue is a common symptom experienced by up to 80% of patients at the time of diagnosis and during follow-up. Unfortunately, current treatments have not been effective in alleviating fatigue. The objective of this study is to evaluate fatigue and investigate any potential muscle involvement in PBC patients.

Methods: We conducted a single-center, cross-sectional study involving 50 patients who suffered from both PBC and fatigue. Muscle biopsies were performed to whom presented muscle weakness. Histopathological analysis was made and also RNA sequencing was performed on muscle biopsies (n=10) as well as 33 normal muscle biopsies. Muscle biopsies were stained for human immunoglobulin and PDC-E2.

Results: Abnormal accumulation of mitochondria in the subsarcolemal region was observed in both optical and electron microscopy. A significant set of immunoglobulin genes was specifically found to be overexpressed in CBP, while over 50 genes related to mitochondrial function were predominantly underexpressed. In muscle biopsies positive for AMA-M2, immunoglobulins were localized in the cytoplasm and colocalized with PDC-E2.

Conclusion: Based on these findings, we can conclude that there is muscular involvement in PBC, and we hypothesise it is likely mediated by AMA-M2 antibodies.






J. Milisenda: None; I. Pinal-Fernandez: None; K. Pak: None; M. Casal-Dominguez: None; Y. Duque-Jaimez: None; G. Garrabou: None; S. Muñoz-Braceras: None; M. Guitart-Manpel: None; J. Torres-Ruiz: None; E. Tobias: None; M. Cano: None; I. Aldecoa: None; J. Grau: None; A. Mammen: None.