Anti-p200 Pemphigoid

What is Anti-p200 Pemphigoid?​

​

Anti-p200 pemphigoid is a rare sub-epidermal blistering disease first described by Zillikens in 1996. This novel disease is defined by tissue-bound immunoglobulins and/or complement C3 along the basement membrane zone (BMZ) and serum autoantibodies targeting a 200-kDa protein localized within the lower lamina lucida of the BMZ. Laminin γ1 has been described as the 200 kDa target antigen recognized by 70% to 90% of patients. Failure of anti-laminin γ1 IgG to show pathogenic effects in vitro and in vivo point to the presence of another autoantigen in anti-p200 pemphigoid. Recently, laminin β4 (LAMB 4) has been identified as additional target antigen of anti-p200 pemphigoid. 

Clinically, anti-p200 pemphigoid may mimic bullous pemphigoid (BP) or other bullous autoimmune diseases. The clinical presentation can be like BP (approx. in 66% patients), linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA), dermatitis herpetiformis and mucous membrane pemphigoid. Patients present with tense blisters, erosions and urticarial plaques, scars
and/or milia can also be present. The extremities (hands and feet) are most frequently involved followed by the trunk, palmoplantar and cephalic involvement. Psoriasis is the most common coexisting dermatosis and it may precede anti-p200 pemphigoid.

​

Laboratory Diagnosis of Anti-p200 Pemphigoid

​

Histology: Histopathology cannot distinguish anti-p200 from other subepidermal blistering diseases. A subepidermal cleft/microvesicles along with a dermal infiltrate of neutrophils or eosinophils or a mix of neutrophils and eosinophils can be observed. 

Direct IF, Skin/Mucosal Biopsy (KSL Beutner Labs Test#001):  This reveals linear deposition of IgG, C3 and sometimes IgA in the dermal-epidermal junction. Deposition of IgG or C3 alone has been reported.

​

Direct IF on 0.1M NaCl split biopsy (KSL Beutner Labs Test#002) 

​

Serology: Indirect immunofluorescence (IIF) test on IM NaCl split skin substrate (KSL Beutner Labs Test #14) reveals binding of anti-p200 pemphigoid antibodies to the dermal side of the split. Reactivity to both roof and floor can be observed. The binding of antibodies with dermal floor is also observed in EBA, bullous lupus and anti-laminin 332 pemphigoid. Reflex testing for type VII collagen antibodies (KSL Beutner Labs Test #61), laminin 332 antibodies (KSL Beutner Labs Test #62) and laminin β4 (NEW KSL Beutner Labs Test #63)  is indicated to determine the autoreactive antigen and manage the disease with appropriate, disease specific treatment.

The new serum test offered by KSL Beutner Laboratories  for laminin β4 antibodies (IgG & IgG4) is an indirect immunofluorescence test on recombinant lamβ4-expressing HEK293 cells (Euroimmun, Lübeck, Germany). This test has  reported sensitivity of 92% and a specificity of 98% for detecting laminin β4 antibodies in anti-p200.

​

Reflex Testing Serum Panels