old-1 Antibody

Definition and Clinical Relevance of Anti-Jo-1 Antibodies

Anti-Jo-1 antibodies are autoantibodies targeting histidyl-tRNA synthetase (HisRS), an enzyme involved in protein synthesis. These antibodies are hallmark biomarkers for anti-synthetase syndrome (ASS), a subset of inflammatory myopathies characterized by muscle weakness, inflammatory arthritis, and ILD .

Key Characteristics:

• Prevalence: Found in ~20–30% of patients with myositis .

• Disease Association: Strongly linked to ILD, with 86% of anti-Jo-1+ individuals developing ILD .

• Pathogenic Role: Induce muscle and lung inflammation via antigen presentation and immune complex deposition .

Antibody Structure

Anti-Jo-1 antibodies belong to the immunoglobulin superfamily, with a Y-shaped structure comprising:

• Fab Region: Two antigen-binding fragments (light and heavy chain variable domains) .

• Fc Region: Mediates interactions with immune effector cells (e.g., macrophages, complement) .

Anti-Jo-1+ ILD Prevalence and Subtypes

Key Findings:

• CRP, CXCL9, CXCL10: Elevated in anti-Jo-1+ ILD, distinguishing it from idiopathic pulmonary fibrosis (IPF) and anti-SRP+ myositis .

• Imaging: High-resolution CT scans show ground-glass opacities and reticular patterns .

Mouse Models

• Passive Immunization: Intramuscular injection of HisRS induces autoantibodies and muscle/lung inflammation .

• Challenges: Bleomycin/cardiotoxin exacerbates lung pathology, linking anti-Jo-1 antibodies to tissue damage .

Therapeutic Implications

• PD-1 Checkpoint Inhibition: Enhances CAR T-cell therapy efficacy by reducing myeloid-derived suppressor cells (MDSCs) .

• Blimp-1 Deficiency: Age-related decline in B-1 cell antibody secretion (IgM/IgG) correlates with reduced Blimp-1 expression .

Biomarker Limitations

• Serum Jo-1 Titers: Correlate with ILD activity but lack specificity for early diagnosis .

• Age-Related Decline: B-1 cells in elderly show reduced IgM secretion and clonal expansion, potentially weakening natural antibody protection .