BackgroundBullous pemphigoid (BP) is the most frequent autoimmune blistering disease mainly affecting elderly patients. Among several published risk factors, a recent post hoc analysis linked anti‐BP180 autoantibodies (AABs) to fatal outcomes in BP. To date, this finding has not been confirmed independently.ObjectiveTo investigate the potential of anti‐BP180‐AAB levels as a marker of prognosis and to identify a cut‐off level indicative of an increased risk for early death. Secondly, to characterize parameters associated with mortality.MethodsRetrospective, single‐centre study of BP patients diagnosed between 2001 and 2012. Analyses included epidemiological and patient‐ and disease‐specific characteristics as well as immunological parameters at diagnosis and during follow‐up. Standardized mortality ratios as well as uni‐ and multivariate regression analyses were calculated.ResultsOne hundred patients (56 women, 44 men) with a median age of 81 years (interquartile range 74–86) were followed up for a median of 775 days (interquartile range 162–1617). One‐year mortality rates were 25.0% implying a 2.4‐fold increased risk of death compared with the general population. High anti‐BP180 autoantibody levels at diagnosis (CI95 1.30–2.89; P = 0.001), dementia (CI95 1.13–6.72; P =0.03), length of hospitalization (CI951.16–2.41; P = 0.01) and age (CI95 1.23–4.19; P = 0.009) correlated significantly with 1‐year mortality. BP180‐AAB concentrations of ≥61 U/mL characterized a subgroup of patients with a particular higher risk for early death compared with the general population (CI95 1.81–3.81; P < 0.0001).ConclusionIn bullous pemphigoid, serum concentrations of BP180 autoantibodies at diagnosis could help to identify patients at risk for death within the first year after diagnosis (cut‐off value 61 U/mL).

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To investigate the molecular mechanisms contributing to senescence-escape in nevus-associated melanoma (NAM). To characterize the associated inflammatory profile of senescenceescaped cells in early melanoma development. Immunohistochemistry for select targets was performed in NAM and de-novo melanoma (DNM) patient samples. Images were evaluated by computer-aided cell-by-cell analysis. A p16-dependent cell line model of naïve, senescent and senescence-escaped cells was established to measure cell-intrinsic mRNA levels of different cell-states. Most regulated molecules were assessed for effects on proliferation and viability in melanoma cells. It is well established that p16 is genetically lost in 50% of all melanoma cases. However, in our set of NAM patient samples and in contrast to DNM, all tumors expressed p16. Most interestingly, the cytoplasmic-to-nuclear ratio of p16 increased more than 2-fold in NAMs (p<.0001) compared to their nevus counterparts. Our results indicate that senescence-escape in NAM is linked to a functional deficiency of p16 due to its accumulation in the wrong cell compartment. We found that the nuclear export system contributes to this altered subcellular localization of p16. Exportin 1 (XPO1) inhibition with KPT-330 reduced melanoma cell proliferation in p16-wild-type, but not in p16-deleted cells. Additionally, we found a marked up-regulation of several pro-inflammatory molecules including COX2, CXCL5, CXCL8, and others upon senescence-escape. Combined targeting of XPO1 and COX2 resulted in synergistic reduction of melanoma cell proliferation in p16-wildtype, NRAS mutant cells, whereas p16-deleted cells were largely unaffected. Our data reveal that dysregulated p16 protein localization is a yet unknown trajectory of melanomagenesis in NAM, which might open up new avenues for individualized melanoma targeting.