Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.

The way a tumor cell dies is believed to influence both its engulfment by dendritic cells (DC) and access of the relevant antigen(s) to the cross-presentation pathway. Here we have studied the effect of lymphokine activated killer (LAK) cells, gamma-radiation and the antimetabolite drug 5-fluorouracil (5-FU) on tumor uptake by HLA-matched DC, and DC presentation of tumor antigens to autologous T lymphocytes. LAK cells and radiation were the best inducers of apoptotic death (Annexin-V+/propidium iodide-) on the gastric cell line KATO III and a primary gastric carcinoma, respectively. The highest rate of tumor uptake by monocyte-derived, granulocyte macrophage colony stimulating factor/interleukin (IL)-4-driven DC was associated with 5-FU, followed by radiation. These treatments also induced high levels of heat shock protein (hsp70). In contrast, only DC that had been taken up 5-FU- or LAK-treated tumors up-modulated IL-12 and presented tumor-associated antigens with increased efficiency, as shown by class I MHC-restricted interferon-gamma release and cytotoxic responses by autologous lymphocytes. Together, these data indicate that apoptotic death induced by anti-cancer therapies can induce distinct patterns of class I MHC cross-presentation of gastric carcinoma-associated antigens to cytotoxic T lymphocyte precursors.

Bullous pemphigoid (BP) is an autoimmune bullous disease caused by circulating autoantibodies toward the hemidesmosomal antigens BP180 and BP230. Cases of BP have been described following vaccinations against tetanus, poliomyelitis, diphtheria, influenza, pneumococcus, meningococcus, hepatitis B and rabies. The putative mechanism by which COVID-19-vaccines may induce BP has not been clarified. An Italian multicentre study was conducted to collect clinical, histopathological and immunopathological data of patients with BP associated with COVID-19-vaccines. Twenty-one cases were collected, including 9 females and 12 males (M/F = 1.3) with a median age at diagnosis of 82 years. Seventeen patients received the COMIRNATY Pfizer-BioNTech vaccine, two the Moderna mRNA-1273 vaccine, one the ChAdOx1/nCoV-19-AstraZeneca/ Vaxzevria vaccine and one received the first dose with the ChAdOx1/nCoV-19-AstraZeneca/Vaxzevria vaccine and the second dose with the COMIRNATY Pfizer-BioNTech vaccine. Median latency time between the first dose of anti-SARS-CoV-2 vaccine and the onset of cutaneous manifestations was 27 days. Median BPDAI at onset was 42. Eleven out of seventeen patients (65%) had positive titres for anti-BP180 antibodies with a median value of 106.3 U/mL on ELISA; in contrast, only five out of seventeen (29%) were positive for anti-BP230 antibodies, with a median of 35.3 U/mL. In conclusion, in terms of mean age, disease severity at diagnosis and clinical phenotype vaccine-associated BP patients seem to be similar to idiopathic BP with an overall benign course with appropriate treatment. On the other hand, the slight male predominance and the reduced humoral response to BP230 represent peculiar features of this subset of patients.

SUMMARYProlactin (PRL) shares structural and functional features with haemopoietic factors and cytokine peptides. Dendritic cells (DC) are involved in both initiating the primary and boosting the secondary host immune response and can be differentiated in vitro from precursors under the effect of granulocyte±macrophage colony-stimulating factor (GM-CSF) plus other factors. Because PRL has been shown to functionally interact with GM-CSF, we have addressed its role on GM-CSFdriven differentiation of DC. Monocytic DC precursors from peripheral blood mononuclear cells (PBMC) were enriched either by adhesion to a plastic surface or CD14-positive selection and cultured for 7 days in serum-free medium containing GM-CSF, interleukin (IL)-4 and PRL, alone or in combination. Cells with large, veiled cytoplasm, expressing major histocompatibility complex (MHC) class II and the costimulatory molecules CD80, CD86 and CD40 and lacking the monocyte marker CD14, were considered as having the phenotype of cytokine-generated DC. Functional maturation was assessed by proliferation and interferon-c (IFN-c) release of allogeneic T lymphocytes. Physiological (10±20 ng/ml) concentrations of PRL interacted synergistically with GM-CSF and the effect was similar to that induced by IL-4 on GM-CSF-driven DC maturation. When used alone, the physiological concentrations of PRL were inhibitory, whereas higher concentrations (80 ng/ml) were stimulatory. The synergistic effect of PRL may in part be caused by its ability to counteract the down-modulation of the GM-CSF receptor observed in serum-free conditions. These data provide further evidence of the signi®cance of PRL in the process of T lymphocyte activation.