Acquired angio-oedema caused by IgA paraprotein

Area of Science:

• Immunology
• Complement System Biology
• Hematology

Background:

• Acquired angio-oedema is a rare condition characterized by recurrent swelling and abdominal pain, often associated with acquired C1-inhibitor deficiency.
• Acquired C1-inhibitor deficiency is typically linked to B-cell malignancies, affecting approximately 50 reported patients.
• The complement system's regulatory pathways are crucial for preventing uncontrolled inflammation.

Observation:

• A patient presented with an 8-year history of recurrent abdominal pain and angio-oedema.
• The patient was diagnosed with acquired C1-inhibitor deficiency.
• Bone marrow analysis revealed an IgA-kappa monoclonal plasma cell population without overt myeloma.

Findings:

• The patient's acquired C1-inhibitor deficiency was caused by IgA-kappa autoantibodies that inactivate C1-inhibitor.
• This represents an extremely rare mechanism for angio-oedema, particularly an IgA isotype autoantibody.
• This is the first reported case of such a condition in a Dutch patient.

Implications:

• Accurate diagnosis of angio-oedema, including rare acquired forms, is critical due to significant therapeutic implications.
• Understanding autoantibody-mediated complement dysregulation expands knowledge of angio-oedema pathogenesis.
• This case underscores the importance of investigating atypical presentations of angio-oedema and C1-INH deficiency.