- Indian Rheumatology association
Sabarinath Mahadevan MBBS, MD, DM, MRCP (Edin.), SCE (RCP UK)
Assistant professor, Institute of Rheumatology, Madras Medical College, Chennai, Tamil Nadu, India.
Mitochondrial transplantation as a novel therapeutic approach in idiopathic inflammatory myopathy.
Mitochondrial transplantation using PN-101 (mitochondria isolated from human umbilical cord mesenchymal stem cells) demonstrates therapeutic potential for idiopathic inflammatory myopathy (IIM), addressing mitochondrial dysfunction and inflammation. IIM patient-derived myoblasts exhibited defective myogenesis, reduced myosin heavy chain expression, and impaired mitochondrial oxidative phosphorylation complexes (e.g., TOM20, NDUFB8). Proinflammatory cytokines such as IFNγ exacerbated these defects, suppressing muscle differentiation.
PN-101 restored adenosine triphosphate (ATP) production in in vitro preclinical models by enhancing cell viability and promoting myogenesis in patient-derived myoblasts from IIM and perforin/granzyme B-treated C2C12 mouse cells. PN-101 reduced muscle inflammation in vivo by lowering IL-6 levels, reversing metabolic shifts, and restoring mitochondrial complex activity more effectively than dexamethasone. PET/MRI confirmed enhanced mitochondrial function.
In this Phase 1/2a trial, nine patients with refractory polymyositis/dermatomyositis received PN-101 intravenously. No severe adverse events occurred, and all achieved at least minimal improvement in IMACS-Total Improvement Scores at 12 weeks. PN-101 promotes mitochondrial repair by enhancing oxidative phosphorylation (OXPHOS) complexes and ATP synthesis. It also exhibits anti-inflammatory effects by suppressing the production of proinflammatory cytokines.
This study provides the first clinical evidence supporting mitochondrial transplantation as a safe, disease-modifying therapy for IIM. It has potential applications in other rheumatic disorders. Larger trials are needed to validate efficacy.1
Evidence of Site-Specific Mucosal Autoantibody Secretion in Rheumatoid Arthritis
This study investigated the presence of anti-modified protein antibodies (AMPA), including anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and anti-acetylated protein antibodies (AAPA), in the mucosal secretions of rheumatoid arthritis (RA) patients. The researchers analyzed paired faecal/ileal wash, saliva, and serum samples from RA patients and healthy volunteers across three independent cohorts.
ACPA, anti-CarP, and AAPA IgA were found in the saliva of seropositive RA patients (prevalence 9%-40%). No AMPA were detected in faeces or ileal wash samples, even though total IgA and anti-E. coli IgA were measurable in faeces, indicating IgA presence. The study suggests that mucosal autoantibody secretion occurs in the oral mucosa of RA patients but not in the lower gastrointestinal tract.2
Urinary Biomarkers Associated with Pathogenic Pathways Reflecting Histologic Findings in Lupus Nephritis.
This study aimed to identify pathogenic pathways and urinary biomarkers for predicting the presence or severity of histologic findings in lupus nephritis (LN). Researchers screened urine samples from active LN patients for 1,305 proteins and quantified renal histologic features. Cluster analysis revealed five histologic subgroups with distinct pathogenic signals.
ELISA validation identified urinary calgranulin B (S100A9), monocyte chemotactic protein 1 (MCP-1), and insulin-like growth factor binding protein 5 (IGFBP-5) as predictors of active glomerular lesions, interstitial inflammation, and interstitial fibrosis, respectively, as confirmed by immunohistochemistry.
The study concludes that renal histologic findings reflect different pathogeneses, and that urinary calgranulin B, MCP-1, and IGFBP-5 levels may help predict the presence and severity of histologic findings in LN.3
