Anti–laminin γ1 pemphigoid (ALG1P) is an autoimmune subepidermal bullous disease characterized by autoantibodies to a 200-kDa acidic noncollagenous glycoprotein of the lower lamina lucida. In contrast, anti–laminin-332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies to various subunits of laminin-332 of the basement membrane. We report the first case to our knowledge of ALG1P with IgG autoantibodies for 3 distinct laminins: α3 and γ2 subunits of laminin-332 and laminin γ1.
A man in his 70s was referred for tense blisters and erosions on the trunk and extremities (Figure 1A and B). No mucosal involvement was observed. He had undergone a dialysis treatment for chronic glomerulonephritis. A skin biopsy specimen taken from a bulla on the right thigh at the previous hospital demonstrated subepidermal separation with infiltration of neutrophils and eosinophils in the blister cavity and the upper dermis (Figure 1C and D). Direct immunofluorescence (IF) of the perilesional skin showed linear deposition of C3 at the basement membrane zone (BMZ). Indirect IF of healthy control human skin showed IgG anti-BMZ antibodies at a 1:20 titer (Figure 1E), which reacted with the dermal side of 1M sodium chloride–split skin (Figure 1F). In immunoblotting of healthy control human dermal extracts, IgG antibodies reacted with the 200-kDa laminin γ1 (Figure 2A). Furthermore, immunoblotting of purified human laminin-332 demonstrated IgG autoantibodies to the 145-kDa and 165-kDa α3 subunits and the 105-kDa γ2 subunit of laminin-332 (Figure 2B). Traces of the 140-kDa β3 subunit were also detected, but the band was too faint to be significant. Although treatment with oral prednisolone, 25 mg/d (0.5 mg/kg/d), alleviated the symptoms, a few blisters still appeared. The addition of colchicine to his treatment regimen, 0.5 mg/d, suppressed blisters completely.
A and B, Clinical presentation of the patient. C and D, Histopathologic findings (hematoxylin-eosin, original magnification ×100 [C] and ×400 [D]); the rectangular area marked in panel C is magnified in panel D. E and F, Indirect immunofluorescence of perilesional skin (E; original magnification ×100) and 1M sodium chloride–split skin (F; original magnification ×200).
A, With normal human dermal extracts, control epidermolysis bullosa acquisita (EBA) serum reacted with the 290-kDa type VII collagen (lane 1), and control anti–laminin γ1 (p200) pemphigoid serum reacted with the 200-kDa laminin γ1 (lane 2); IgG antibodies from our patient reacted with the laminin γ1 antigen (lane 3, pointer). B, With purified human laminin-332, control anti–laminin-332 type mucous membrane pemphigoid (MMP) serum reacted with the 165-kDa α3, 145-kDa α3, 140-kDa β3, and 105-kDa γ2 subunits (lane 1). A reference normal control serum showed negative results (lane 2). IgG antibodies from this patient reacted with the α3 and γ2 subunits of laminin-332 (lane 3, pointers).
Immunoblotting detected IgG autoantibodies to α3 and γ2 subunits of laminin-332 and laminin γ1. Clinically, most reported cases of ALG1P present with tense blisters and urticarial lesions without mucosal involvement, closely resembling bullous pemphigoid.1 In contrast, anti–laminin-332 MMP, which accounts for 10% to 20% of MMP, shows mucosal involvement. Because our case did not show mucosal involvement, a diagnosis of MMP is unlikely. Considering clinical findings, we diagnosed our case as ALG1P accompanied by autoantibodies to α3 and γ2 subunits of laminin-332.
Our patient was receiving dialysis treatment for chronic glomerulonephritis. Mitate et al2 also reported a case of pemphigoid with antibodies to both laminins γ1 and γ2 after rejection response to a transplanted kidney. Laminin is a major component of the renal glomerular BMZ and mesangium. Setty et al3 reported that IF studies with laminin chain–specific antibodies detected expression of α2, β1, and γ1 subunits in the normal mesangium and expression of α5, β2, and γ1 subunits in normal glomerular BMZ. In our case, it may be speculated that the autoantibodies to laminin γ1 cause both subepidermal blisters in the skin and glomerulonephritis in the kidney.
Recently, the C terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid, and the disease was renamed as ALG1P.4 However, Vafia et al5 reported that human IgG specific to laminin γ1 did not induce dermal-epidermal separation ex vivo, although serum samples from patients with “anti-p200 pemphigoid” did.5 They concluded that autoantibodies in anti-p200 pemphigoid serum samples are pathogenic, while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid.
In summary, we report the first case to our knowledge of ALG1P with IgG autoantibodies for 3 distinct laminins. It remains unknown whether the reactivity with multiple components of BMZ is caused by independent autoantibodies or cross-reactive autoantibodies. Accumulation of cases like our case should give us a clue to answer this question.
Corresponding Author: Masahiro Kamata, MD, PhD, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan (email@example.com).
Published Online: October 23, 2013. doi:10.1001/jamadermatol.2013.5358.
Conflict of Interest Disclosures: None reported.
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