What does Anti-Ro Antibody (Anti-Ro Ab) attack in patients with Sjögren's syndrome or Systemic Lupus Erythematosus (SLE)?

What Anti-Ro Antibodies Attack

Anti-Ro (SSA) antibodies target a ribonucleoprotein complex composed of small single-stranded RNAs (hYRNAs) bound to peptides of 60 kDa, 52 kDa, or 54 kDa molecular weight, which are normally found in the nucleus and cytoplasm of cells throughout the body. 1

Molecular Target Structure

Anti-Ro antibodies recognize a specific autoantigen complex with the following characteristics:

• The Ro complex exists in four molecular forms based on peptide composition: lymphocyte Ro with 60 kDa peptide, erythrocyte Ro with 60 kDa peptide, lymphocyte Ro with 52 kDa peptide, and erythrocyte Ro with 54 kDa peptide 1

• This complex is ubiquitously distributed across most tissues and cells, including erythrocytes, platelets, lacrimal glands, salivary glands, cardiac conduction tissue, and skin 1

• The Ro antigen likely participates in RNA transcription processes, given its ability to bind nucleic acids and structural homology with gene regulation proteins 1

Tissue Distribution and Clinical Consequences

The widespread tissue distribution of Ro antigens explains the diverse clinical manifestations when antibodies attack these targets:

Glandular Tissue

• Lacrimal and salivary glands are infiltrated by lymphocytes in Sjögren's syndrome, resulting in dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) 2
• This glandular dysfunction affects approximately 0.4% of the general population, with women affected 20 times more frequently than men 2

Cardiac Conduction System

• Fetal cardiac conduction tissue is particularly vulnerable, with anti-Ro/SSA antibodies causing complete heart block in approximately 2% of first pregnancies and 13-18% of subsequent pregnancies in anti-Ro positive mothers 3
• Congenital heart block is irreversible, with approximately 20% mortality in utero or within the first year of life, and more than half requiring pacemaker placement 3

Skin and Cutaneous Structures

• Anti-Ro antibodies are strongly associated with photosensitive skin rashes, particularly subacute cutaneous lupus erythematosus (SCLE), due to ultraviolet radiation causing translocation of Ro antigens to cell membranes where they become accessible to antibodies 4, 1
• Cutaneous manifestations include interface dermatitis with superficial vascular plexus density reduction in photodistributed areas 5

Vascular Endothelium

• Antibody-mediated endothelial cell injury can result in vasculopathy affecting multiple organ systems, including cutaneous, cardiac, peripheral, and central nervous systems 5
• Vasculopathic reactions manifest as livedo, perniosis, palpable purpura, and thrombogenic complications 5

Hematologic Cells

• Erythrocytes and platelets express Ro antigens, leading to hematologic cytopenias including anemia and thrombocytopenia in anti-Ro positive patients 4, 6

Pathogenic Mechanisms

Environmental triggers cause abnormal antigen exposure:

• Ultraviolet radiation exposure induces translocation of the Ro complex from its normal intracellular location to nucleocytoplasmic and membrane sites, making it accessible to circulating antibodies 1

• Viral infections may similarly trigger abnormal Ro antigen expression and localization, initiating the autoimmune response 1

• Once antibodies bind to surface-expressed Ro antigens, complement activation and direct cellular injury occur, particularly in tissues with high Ro expression like cardiac conduction tissue and glandular epithelium 3, 5

Clinical Significance by Disease Context

In Sjögren's Syndrome

• Anti-Ro antibodies are present in the majority of primary Sjögren's patients and score 3 points in the classification criteria (threshold ≥4 points for diagnosis) 2
• These patients have approximately 5% lifetime risk of lymphoma, particularly when accompanied by low C4 complement levels 2

In Systemic Lupus Erythematosus

• Anti-Ro/SSA antibodies have prognostic value and are associated with photosensitive rashes, hematologic abnormalities, and neonatal lupus risk 3, 4
• The combination of anti-Ro with anti-dsDNA or anti-Smith antibodies suggests SLE rather than isolated Sjögren's syndrome 7

In Pregnancy

• Maternal anti-Ro antibodies cross the placenta and attack fetal cardiac conduction tissue between weeks 16-26 of gestation, the critical window for congenital heart block development 3
• Serial fetal echocardiography is conditionally recommended weekly during this period for mothers with prior affected infants, and less frequently for first pregnancies 3