In a patient with pemphigus vulgaris, what type of autoantibodies (IgA or IgG) are typically present on immunofluorescence?

Pemphigus Vulgaris Autoantibodies on Immunofluorescence

In pemphigus vulgaris, IgG autoantibodies—not IgA—are characteristically present on immunofluorescence, depositing in the intercellular spaces between keratinocytes. 1

Diagnostic Immunofluorescence Pattern

Direct Immunofluorescence (DIF)

• The gold standard for diagnosis shows IgG and/or complement (C3) deposited in an intercellular pattern on the cell surfaces of epithelial keratinocytes (between keratinocytes, not at the basement membrane). 1, 2
• This intercellular "chicken wire" or "fishnet" pattern of IgG deposition in the epidermis is pathognomonic for pemphigus vulgaris and distinguishes it from other blistering diseases. 1, 2
• DIF must be performed on perilesional intact skin or clinically uninvolved skin (not from within the blister itself). 1, 2

IgG Subclass Specificity

• The predominant autoantibody is IgG4 subclass, found in 100% of active pemphigus vulgaris cases, followed by IgG1 which is present in approximately 83% of cases. 3, 4
• IgG4 is the pathogenic subclass most closely related to disease activity and recognition of pathogenic epitopes on desmoglein 3 (and desmoglein 1 in mucocutaneous disease). 3, 4
• IgA autoantibodies are exceedingly rare in pemphigus vulgaris—only 2 out of 49 cases in one study showed any IgA reactivity, and this was associated with atypical pustular presentation. 4

Why IgG, Not IgA?

The pathophysiology of pemphigus vulgaris is driven by IgG autoantibodies targeting desmosomal proteins (primarily desmoglein 3, with 50-60% of patients also having desmoglein 1 antibodies). 1, 5

Key Distinguishing Features from IgA Diseases

• IgA-mediated autoimmune blistering diseases (such as IgA pemphigus or linear IgA disease) show completely different clinical presentations and immunofluorescence patterns. 2
• In pemphigus vulgaris, the suprabasal acantholysis and intraepithelial blistering is caused specifically by IgG antibodies disrupting keratinocyte adhesion. 1

Practical Diagnostic Algorithm

Biopsy Requirements

1. Take two separate biopsies when pemphigus vulgaris is suspected: 1, 2

   • One from an intact blister or erosion edge for histology (place in formalin)
   • One from perilesional intact skin for DIF (transport in normal saline if processing within 24 hours, otherwise use Michel's fixative) 1, 2

2. For isolated oral disease, obtain biopsy from perilesional oral mucosa for histology and from uninvolved buccal mucosa for DIF. 1

Expected DIF Results

• Positive: Intercellular IgG deposits in a cell surface pattern throughout the epidermis 1, 2
• Sensitivity of DIF is 89% in oral biopsies and 85% for indirect immunofluorescence (IIF). 1, 5

Indirect Immunofluorescence (Serum Testing)

• IIF detects circulating IgG autoantibodies in serum but is less sensitive than DIF (positive in up to 80% of cases). 1
• Titers are predominantly IgG4 subclass and correlate with disease activity, though the relationship is imperfect. 1, 3

Common Pitfall to Avoid

Do not confuse pemphigus vulgaris (intercellular IgG) with bullous pemphigoid (linear IgG and/or C3 at the dermoepidermal junction). 1, 2, 6 The location and pattern of immunoglobulin deposition are completely different:

• Pemphigus vulgaris: Intercellular IgG between keratinocytes 1, 2
• Bullous pemphigoid: Linear IgG/C3 along the basement membrane zone 1, 2, 6