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BACKGROUND. Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS. We performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes. RESULTS. Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of [CD8.sup.+] T cells toward a terminally differentiated/senescent phenotype. In agreement, [CD4.sup.+] T and [CD8.sup.+] T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION. The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms. FUNDING. This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the 'Excellence Departments 2018-2022 Project') derived from Ministero dell'Istruzione, dell'Universita e della Ricerca (Italy)., Introduction SARS-CoV-2 is the etiological agent of coronavirus disease 19 (COVID-19) and belongs to the same group of RNA viruses that caused SARS and Middle East respiratory syndrome (MERS) in [...]

BACKGROUND. Immunization against SARS-CoV-2, the causative agent of COVID-19, occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last. METHODS. We performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to 1 year after infection and following mRNA vaccination in naive individuals and individuals recovered from COVID-19 infection. RESULTS. We found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly, especially in naive individuals. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naive individuals, whereas it was ineffective in previously SARS-CoV-2-infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to 1 year following natural infection in a cohort of unvaccinated individuals. CONCLUSION. Short-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4* T cells may protect from severe disease development. In naive individuals, a booster dose restored optimal antispike immunity, whereas the needs for vaccinated individuals who have recovered from COVID-19 have yet to be defined. FUNDING. This study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018-2022), the University of Florence (project RICTD2122), the Italian Ministry of Health (COVID-2020-12371849), and the region of Tuscany (TagSARS CoV 2)., Introduction Immunization against SARS-CoV-2, the causative agent of COVID-19 occurs via natural infection or vaccination. As of December 20, 2021, more than 273 million people have been infected worldwide, with [...]

Background: Patients with B-cell lymphoma are a fragile category of subjects, particularly exposed to infections and characterized by an impaired vaccination response due to the disease itself and, even more, to the chemotherapy regimen. For this reason, extensive knowledge of the immune response status of these subjects is of fundamental importance to obtain possible indications for a tailored immunization strategy. Methods: We enrolled two cohorts of patients with B-cell lymphoma under rituximab treatment or 3-24 months after treatment. In all patients, we evaluated both humoral and cellular immunological memory toward SARS-CoV-2, after standard vaccination and upon one booster dose. Results: We observed no Spike-specific IgG production in patients (n = 25) under anti-CD20 treatment, whereas patients (n = 16) vaccinated after the completion of chemotherapy showed a higher humoral response. Evaluating SARS-CoV-2-specific T-cell response, we found that patients in both cohorts had developed robust cellular immunity after vaccination. Of the 21 patients (51%) that experienced a breakthrough SARS-CoV-2 infection, only six patients developed severe disease. Interestingly, these six patients had all been treated with rituximab plus bendamustine. Notably, we observed that Spike-specific IgG levels in patients treated with rituximab plus bendamustine were absent or lower compared with those in patients treated with rituximab plus other chemotherapy, whereas Spike-specific T-cell response was not different based on chemotherapy regiment. Discussion: Our results show that, in patients with B-cell lymphoma under rituximab therapy, anti-SARS-CoV-2 mRNA vaccination induces a weak or absent humoral response but a consistent T-cell response. In addition, chemotherapy regimens with bendamustine further reduce patients' ability to mount a Spike-specific humoral response even after a long time period from chemotherapy discontinuation. These results provide evidence that different chemotherapeutics display different immunosuppressive properties that could be taken in to account in the choice of the right drug regimen for the right patient. Moreover, they question whether immunocompromised patients, particularly those treated with bendamustine, need interventions to improve vaccine-induced immune response. [ABSTRACT FROM AUTHOR]

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV- 2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID- 19-recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike-specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19-recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19-recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19-recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity., Introduction As of April 4, 2021, more than 130.4 million people have been diagnosed with COVID-19 worldwide, with more than 2.8 million confirmed deaths (1). COVID-19 is associated with high [...]

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood. The disease etiology remains largely unknown; however, a key role in JIA pathogenesis is surely mediated by T cells. T‐lymphocytes activity is controlled via signals, known as immune checkpoints. Delivering an inhibitory signal or blocking a stimulatory signal to achieve immune suppression is critical in autoimmune diseases. However, the role of immune checkpoints in chronic inflammation and autoimmunity must still be deciphered. In this study, we investigated at the single‐cell level the feature of T cells in JIA chronic inflammation, both at the transcriptome level via single‐cell RNA sequencing and at the protein level by flow cytometry. We found that despite the heterogeneity in the composition of synovial CD4+ and CD8+ T cells, those characterized by PD‐1 expression were clonally expanded tissue‐resident memory (Trm)‐like cells and displayed the highest proinflammatory capacity, suggesting their active contribution in sustaining chronic inflammation in situ. Our data support the concept that novel therapeutic strategies targeting PD‐1 may be effective in the treatment of JIA. With this approach, it may become possible to target overactive T cells regardless of their cytokine production profile. [ABSTRACT FROM AUTHOR]

Anti-RuvBL1/2 autoantibodies have recently been detected in patients with systemic sclerosis (SSc) and scleromyositis overlap syndromes. These autoantibodies exhibit a distinct speckled pattern in an indirect immunofluorescent assay on Hep-2 cells. We report the case of a 48 year old man with facial changes, Raynaud's phenomenon, puffy fingers, and muscle pain. A speckled pattern on Hep-2 cells was identified, but the conventional antibody testing was negative. Based on the clinical suspicion and the ANA pattern, further testing was sought demonstrating anti-RuvBL1/2 autoantibodies. Hence, a review of the English literature was performed to define this newly emerging clinical–serological syndrome. With the one here reported, a total of 52 cases have been described to date (December 2022). Anti-RuvBL1/2 autoantibodies are highly specific for SSc and are associated with SSc/PM overlaps. Apart from myopathy, gastrointestinal and pulmonary involvement are frequently observed in these patients (94% and 88%, respectively). [ABSTRACT FROM AUTHOR]

Background: People Living With HIV (PLWH), with advanced disease, lower CD4+ T cell counts or an unsuppressed HIV viral load can have a suboptimal vaccine response. For this reason, in the current COVID-19 pandemic, they represent a prioritized population for the SARS-CoV-2 fourth (or second booster) vaccine dose. This work aims to investigate the effects of a second booster on the reactivation of the spike-specific humoral and cell-mediated immune responses in PLWH. Methods: A total of eight PLWH, who received a fourth dose of the original mRNA vaccines were enrolled. They were evaluated before and then 7 days, 1 month and 2 months after the injection. The humoral response was assessed via a chemiluminescent immunoassay. Immunophenotyping and the functional evaluation of the SARS-CoV-2-specific cellular immune responses were performed via flow cytometry. Results: Anti-spike IgG levels were above the cut-off value for all subjects at all timepoints. The spike-specific CD4+ T cell response was reactivated one week after the fourth vaccine dose, and on average declined at two months post-vaccination. A similar trend was observed for the spike-specific B cells. A low percentage of spike-specific CD4+ T cells was activated by the B.1.1.529 BA.1 Omicron-spike mutated peptides, and the majority of these cells were reactive to the conserved portions of the spike protein. Similarly, the majority of the spike-specific memory B cells were able to bind both Wuhan and Omicron-spike entire protein. Conclusions: Spike-specific adaptive immune responses are transiently reactivated in PLWH following the fourth mRNA vaccine dose. The breadth of the immune responses to the mutated spike protein provides insight on the possible cross-reactivity for the SARS-CoV-2 variants of concern (VOCs). [ABSTRACT FROM AUTHOR]

X-linked hyper-IgM (XHIGM) syndrome is caused by mutations of the CD40LG gene, encoding the CD40L protein. The clinical presentation is characterized by early-onset infections, with profound hypogammaglobulinemia and often elevated IgM, susceptibility to opportunistic infections, such as Pneumocystis jirovecii pneumonia, biliary tract disease due to Cryptosporidium parvum , and malignancy. We report a 41-year-old male presenting with recurrent leishmaniasis, hypogammaglobulinemia, and myopathy. Whole-exome sequencing (WES) identified a missense variant in the CD40LG gene (c.107T>A, p.M36K), involving the transmembrane domain of the protein and a missense variant in the carnitine palmitoyl-transferase II (CPT2; c.593C>G; p.S198C) gene, leading to the diagnosis of hypomorphic XHIGM and CPT2 deficiency stress-induced myopathy. A review of all the previously reported cases of XHIGM with variants in the transmembrane domain showcased that these patients could present with atypical clinical features. Variants in the transmembrane domain of CD40LG act as hypomorphic generating a protein with a lower surface expression. Unlike large deletions or extracellular domain variants, they do not abolish the interaction with CD40, therefore preserving some biological activity. [ABSTRACT FROM AUTHOR]

Although accumulating data have investigated the effect of SARS-CoV-2 mutations on antibody neutralizing activity, less is known about T cell immunity. In this work, we found that the ancestral (Wuhan strain) Spike protein can efficaciously reactivate CD4+ T cell memory in subjects with previous Alpha variant infection. This finding has practical implications, as in many countries only one vaccine dose is currently administered to individuals with previous COVID-19, independently of which SARS-CoV-2 variant was responsible of the infection. We also found that only a minority of Spike-specific CD4+ T cells targets regions mutated in Alpha, Beta and Delta variants, both after natural infection and vaccination. Finally, we found that the vast majority of Spike-specific CD4+ T cell memory response induced by natural infection or mRNA vaccination is conserved also against Omicron variant. This is of importance, as this newly emerged strain is responsible for a sudden rise in COVID-19 cases worldwide due to its increased transmissibility and ability to evade antibody neutralization. Collectively, these observations suggest that most of the memory CD4+ T cell response is conserved against SARS-CoV-2 variants of concern, providing an efficacious line of defense that can protect from the development of severe forms of COVID-19. [ABSTRACT FROM AUTHOR]

Melanocyte-specific immune response in a patient with multiple regressing nevi and a history of melanoma. After reviewing the literature (Table 1), we found that some cases of vitiligo related to SARS-CoV-2 vaccination had been reported,6-12 while no cases of eruptive halo nevi after COVID-19 vaccination had been described so far. Dear Editor, Halo nevi, also known as Sutton nevi, are characterized by the development of a rim of depigmentation around a nevus. [Extracted from the article]

Objective: Although the adaptive immune response to SARS‐CoV‐2 has been characterised in the acute and early convalescent phase of the disease, few studies explore whether natural infection elicits long‐lasting immunological memory in recovered individuals. In this work, we aimed to assess the maintenance of immunological memory to SARS‐CoV‐2. Methods: We evaluated the long‐term virus‐specific cellular and humoral immune response in the members of an Italian Serie A football team, who experienced a cluster of COVID‐19 in March 2020, which was strictly evaluated in the following months. Results: Our results highlight a heterogeneous magnitude of immunological memory at 5 months after infection. Indeed, 20% of the subjects displayed a weak cellular and humoral memory to SARS‐CoV‐2, suggesting that they may be at higher risk of reinfection. In addition, a history of symptomatic COVID‐19 was associated with higher levels of SARS‐CoV‐2‐reactive CD4+ T cells and specific antibody levels than in asymptomatic individuals. Conclusion: Collectively, these data demonstrate that immunity to SARS‐CoV‐2 is maintained five months postinfection even if the magnitude of response is heterogeneous among individuals. This finding suggests that some COVID‐19‐recovered subjects may benefit from vaccination. [ABSTRACT FROM AUTHOR]

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes. Author summary: The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is markedly affecting the world population. Here we report about the small-molecule profile of patients hospitalized during the first wave of the COVID-19 pandemic in Florence (Italy). Using magnetic resonance spectroscopy, we showed that the infection induces profound changes in the metabolome. The analysis of the specific metabolite changes and correlations with clinical data enabled the identification of potential biochemical determinants of the disease fingerprint. We also followed how metabolic alterations revert towards those of the control group upon treatment with tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor. These results open up possibilities for the monitoring of novel patients and their individual response to treatment. [ABSTRACT FROM AUTHOR]

The late nineteenth and early twentieth centuries in Egypt saw new concepts of community emerge to replace the extant, traditional forms of identity based on local loyalties. This paper will explore the role played by language and journalism in this re-imagining of identity, and its use by the elite in shaping perceptions of the Egyptian people, nation and language. A fundamental element of this process was the development in the use of the term ummah in the discourse of many thinkers of the Nahḍah, from its meaning signifying the global community of Muslim believers, into a symbol of the modern nation-state, a re-interpretation which I discuss drawing, notably, on the unpublished writings of the journalist Aḥmad Luṭfī al-Sayyid. This perspective enables an exploration both of the competition between traditionalist values and the secular, multicultural model of early Egyptian nationalism, and of the multifarious colonial influences on the pro-Europe anelite in this struggle for a vision of Egypt's future. [ABSTRACT FROM AUTHOR]

• IL-6 has a central role in COVID-19 cytokine storm and into the promotion of coagulation thus exerting prothrombotic effect. • Tocilizumab improved the alveolar-arterial oxygen gradient and the vascular radiologic score at 1 week after treatment. • By blocking the IL-6 axis tocilizumab may improve lung perfusion in patients with severe COVID-19 pneumonia. As of October 2020 management of Coronavirus disease 2019 (COVID-19) is based on supportive care and off-label or compassionate-use therapies. On March 2020 tocilizumab - an anti-IL-6 receptor monoclonal antibody - was suggested as immunomodulatory treatment in severe COVID-19 because hyperinflammatory syndrome occurs in many patients similarly to the cytokine release syndrome that develops after CAR-T cell therapy. In our retrospective observational study, 20 severe COVID-19 patients requiring intensive care were treated with tocilizumab in addition to standard-of-care therapy (SOC) and compared with 13 COVID-19 patients receiving only SOC. Clinical respiratory status, inflammatory markers and vascular radiologic score improved after one week from tocilizumab administration. On the contrary, these parameters were stable or worsened in patients receiving only SOC. Despite major study limitations, improvement of alveolar-arterial oxygen gradient as well as vascular radiologic score after one week may account for improved pulmonary vascular perfusion and could explain the more rapid recovery of COVID-19 patients receiving tocilizumab compared to controls. [ABSTRACT FROM AUTHOR]

Summary: SARS‐CoV‐2 is responsible for a new infectious disease (COVID‐19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS‐CoV‐2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profiles and the subset distribution of myeloid cells and their correlation with disease progression in 40 COVID‐19 patients at different stages of disease. COVID‐19 patients showed a decrease in the absolute number of plasmacytoid and myeloid dendritic cells, different subset distribution of monocytes and different activation patterns of both monocytes and neutrophils, coupled to a significant reduction of HLA‐DR monocyte levels. We found that some of these alterations are typical of all COVID‐19 patients, while some others vary at different stages of the disease and correlate with biochemical parameters of inflammation. Collectively, these data suggest that not only the lymphoid, but also the myeloid compartment, is severely affected by SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

The characterization of cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 is fundamental to understand COVID‐19 progression and the development of immunological memory to the virus. In this study, we detected T‐cells reactive to SARS‐CoV‐2 proteins M, S, and N, as well as serum virus‐specific IgM, IgA, IgG, in nearly all SARS‐CoV‐2 infected individuals, but not in healthy donors. Virus‐reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune‐checkpoint molecules PD1 and TIGIT. Of note, we detected antigen‐specific adaptive immune response both in asymptomatic and symptomatic SARS‐CoV‐2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell‐mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life‐threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region. Methods: All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow‐up were collected by the clinicians. Results: Nine cases were found, with a mean age of 76 years, ranging in size between 0.3 and 3.5 cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo‐papillary and solid‐tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP‐15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases. In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease. Conclusion: As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow‐up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma. [ABSTRACT FROM AUTHOR]

Background: Targeted therapies (TT), combination immunotherapy (CMI), and monoimmunotherapy (MI) in combination with radiotherapy (CRI) or not are commonly used in patients with melanoma brain metastases, but studies that directly compare these strategies are lacking. The current meta-analysis aimed to better elucidate their activity and efficacy.Methods: A systematic search of MEDLINE, Embase, and conference proceedings up to January 2019 was performed to identify trials investigating combination TT, monotargeted TT (mono TT), MI, CMI, and CRI in melanoma brain metastases. The outcomes considered were progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) as evaluated at both intracranial and extracranial sites. Random effects models were used to compare the different therapeutic strategies.Results: A total of 15 trials were included that provided 1132 patients for analyses. CMI demonstrated a statistically significant better OS compared with MI (P = .03, P = .05, and P = .03, respectively, at 6 months, 18 months, and 24 months) and combination TT (P = .04 and P = .03, respectively, at 18 months and 24 months). CMI demonstrated a statistically significant better PFS compared with combination TT (P < .001 at 12 months and 18 months), MI (P = .02, P < .02, and P = .05, respectively, at 6 months, 12 months, and 18 months), and mono TT (P < .001 at 6 months, 12 months, and 18 months). The intracranial objective response rate was higher with CMI compared with mono TT (P < .001) and MI (P < .001), whereas there was no difference between CMI and combination TT.Conclusions: The results of the current meta-analysis suggested that CMI increases long-term PFS and OS compared with MI and combination TT. Combination TT and CMI are associated with a similar intracranial response rate. The role of systemic therapy in combination with radiotherapy remains to be better elucidated. [ABSTRACT FROM AUTHOR]

Background: Lichenoid keratosis is a benign cutaneous lesion exhibiting many clinical faces and different dermoscopic features. Objective: This study aims to determine the pattern of different clinical subtypes of lichenoid keratosis and to establish whether there is any correlation between the clinical variants of lichenoid keratosis and their dermoscopic appearance. Methods: We retrospectively analyzed the medical records and clinical database of patients who had received a histological diagnosis of lichenoid keratosis. Based on the literature review and the clinical-dermoscopic features of lichenoid keratosis, we divided the lesions into 6 clinical subtypes to evaluate potential correlations between clinical and dermoscopic features in all subtypes. Results: Fifty-one lesions were included in this clinical study. Preoperatively, only 1.9% of cases were clinically diagnosed as lichenoid keratosis, and the most common misdiagnosis was basal cell carcinoma (52.9%). We identified 6 subtypes of lichenoid keratosis and their corresponding dermoscopic features and clues. Conclusion: Since lichenoid keratosis has no pathognomonic dermoscopic clues and it is commonly misdiagnosed as malignant skin neoplasms, such as basal cell carcinoma and melanoma, improving the knowledge of both clinical and dermoscopic variability of lichenoid keratosis may help dermatologists to reduce unnecessary surgery and to reduce health care spending. [ABSTRACT FROM AUTHOR]

High levels of TGF 1 induce the expression of Nrp1 on lung ILC2s (1); Nrp1 can bind activated or latent forms of TGF 1 and can act as co-receptor of TGF 1R. Like Th2 cells, ILC2s express GATA3 and exploit their effector function mainly producing IL-13 and IL-5.1 ILC2s are rapidly activated upon stimulation by epithelium-derived cytokines such as TSLP, IL-33, and IL-25. Selective targeting of TGF 1 via neutralizing monoclonal antibodies (mAbs) may suppress the TGF 1-Nrp1 pathway in lung-resident ILC2s, thereby controlling inflammation. [Extracted from the article]

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and significantly impacts patients' lives, particularly in its severe forms. AD clinical presentation varies over the course of the disease, throughout different age groups, and across ethnicities. AD is characterized by a spectrum of clinical phenotypes as well as endotypes. Starting from the current description of AD pathogenesis, this review explores the rationale of approved AD therapies from emollients to biologicals and introduces novel promising drugs. [ABSTRACT FROM AUTHOR]

• A dysregulation in the immune response against SARS-CoV-2 occurs in severe COVID-19 patients. • 6 hallmarks define abnormalities of innate and adaptive immunity in COVID-19. • Innate immunity alterations include hyperinflammation and dysregulation of type I interferon activity and myeloid response. • Lymphocyte alterations include reduced cell counts, impaired functionality and heterogeneous specific response to SARS-CoV-2. • Understanding immune dysregulation in COVID-19 will be crucial to design appropriate therapeutic interventions. One and half year following the occurrence of COVID-19 pandemic, significant efforts from laboratories all over the world generated a huge amount of data describing the prototypical features of immunity in the course of SARS-CoV-2 infection. In this Review, we rationalize and organize the main observations, trying to define a "core" signature of immunity in COVID-19. We identified six hallmarks describing the main alterations occurring in the early infection phase and in the course of the disease, which predispose to severe illness. The six hallmarks are dysregulated type I IFN activity, hyperinflammation, lymphopenia, lymphocyte impairment, dysregulated myeloid response, and heterogeneous adaptive immunity to SARS-CoV-2. Dysregulation and exhaustion came out as the trait d'union, connecting abnormalities affecting both innate and adaptive immunity, humoral and cellular responses. [ABSTRACT FROM AUTHOR]

We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old man receiving pembrolizumab to treat advanced lung cancer. The patient experienced hypothyroidism, myalgia, skin involvement, dyspnoea and diarrhoea. Laboratory tests revealed raised inflammatory markers, hypercreatinekinasemia and anti-MDA5 autoantibodies. Electroneuromyography and pathognomonic signs on physical examination confirmed the diagnosis of pauci-myopathic dermatomyositis. Pembrolizumab was discontinued and immunosuppressive therapy led to rapid and progressive improvement, with complete remission of dermatomyositis. This case report widens the spectrum of systemic immune-related adverse events associated with pembrolizumab.

From the discovery of IgE to the in-depth characterization of Th2 cells and ILC2, allergic inflammation has been extensively addressed to find potential therapeutical targets. To date, omalizumab, an anti-IgE monoclonal antibody, and dupilumab, an anti-IL-4 receptor α monoclonal antibody, represent two pillars of biologic therapy of allergic inflammation. Their increasing indications and long-term follow-up studies are shaping the many different faces of allergy. At the same time, their limitations are showing the intricate pathogenesis of allergic diseases.

Patients with melanoma brain metastases (MBM) have a dismal prognosis, but the unprecedented advances in systemic therapy alone or in combination with local therapy have now extended the 1-year overall survival rate from 20-25% to nearing 80-85%, mainly in asymptomatic patients. The histopathological and molecular characterization of MBM and the understanding of the microenvironment are critical to more effectively manage patients with advanced melanoma and to design biologically driven clinical trials. This review aims to give an overview of the main histopathological features and the immune-molecular aspects of MBM., Competing Interests: Financial & competing interests disclosure M Mandalà: Honoraria or Advisory Board of Roche, Novartis, BMS, MSD, Pierre Fabre. Research grant: Roche, Novartis. D Massi: Honoraria or Advisory Board of Novartis, Bayer, Pierre-Fabre, Sanofi, MSD, Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Daniela Massi.)