Checkpoint Inhibition May Trigger the Rare Variant of Anti-LAD-1 IgG-Positive, Anti-BP180 NC16A IgG-Negative Bullous Pemphigoid.
Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by an autoimmune response to type XVII collagen (BP180). The generation of anti-BP180-NC16A IgG autoantibodies is considered to be central to the pathogenesis of BP, in part due to the close correlation between serum concentration and disease activity. However, ~60% of BP patients also generate IgG autoantibodies against LAD-1, the soluble 120 kDa ectodomain of BP180. Whilst the pathogenic significance of anti-LAD-1 IgG remains unclear, it may be sufficient to precipitate the development of BP, even in the absence of anti-BP180-NC16A IgG, based on several case reports in Japanese patients. There is increasing recognition that immune-checkpoint inhibitors may trigger and/or exacerbate BP as an immune-related adverse event (irAE). Until now, all of these cases have been associated with the induction of anti-BP180-NC16A IgG. Here, we report the case of a female Caucasian patient who developed BP during treatment with the programmed cell death protein 1 (PD-1) inhibitor nivolumab. Intriguingly, the patient exclusively generated anti-LAD-1 IgG, suggesting that anti-LAD-1 IgG was responsible for the development of her autoimmune blistering dermatosis. This is the first such case documented in a non-Japanese patient, thus, lending further support to the pathogenic relevance of anti-LAD-1 IgG in BP.
['Sadik|Christian D|CD|', 'Langan|Ewan A|EA|', 'Grätz|Victoria|V|', 'Zillikens|Detlef|D|', 'Terheyden|Patrick|P|']
D000368:Aged D000074322:Antineoplastic Agents, Immunological D001323:Autoantibodies D001324:Autoantigens D004797:Enzyme-Linked Immunosorbent Assay D005260:Female D005455:Fluorescent Antibody Technique D006801:Humans D007074:Immunoglobulin G D007166:Immunosuppressive Agents D008545:Melanoma D024041:Non-Fibrillar Collagens D010391:Pemphigoid, Bullous D012867:Skin D016896:Treatment Outcome
bullous pemphigoid LAD-1 nivolumab checkpoint inhibitors melanoma skin inflammation