For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel represent, at the same time, barrier and connection between the inner and the outer sides of the body. The most important genetic correlations involve the chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in innate and adaptive immunity. The genetic background represents the substrate to the common immune processes involved in psoriasis and IBD. In the past, psoriasis and IBD were considered Th1-related disorders. Nowadays the role of new T cells populations has been highlighted. A key role is played by Th17 and T-regs cells as by the balance between these two cells types. New cytokines and T cells populations, as IL-17A, IL-22, and Th22 cells, could play an important pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support the hypothesis of a common pathogenesis.

Inhibitors of RAF inhibit the MAPK pathway that plays an important role in the development and progression of those melanoma carrying the V600E BRAF mutation, but there’s a subset of such patients who do not respond to the therapy. Various mechanisms of drug resistance have been proposed which include the clonal heterogeneity of the tumor. We have studied a population of nodular melanoma to investigate the intratumor and intertumor heterogeneity by Laser Capture Microdissection (LCM) analysis. Our results showed that BRAF and NRAS mutations were detected in 47% and 33% of nodular melanoma, respectively, and that there is a discrepancy in mutational pattern of tumoral sample because in the 36% of patients a different mutation, in at least 1 area of the tumor, was found by LCM analysis, giving evidence of the presence of different clonal cells populations. Moreover, we found that mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens and we observed that when the 2 different mutations were present one is a high-frequency mutation and the other is a low-frequency mutation. This was more evident in lymphonodal metastasis that resulted from wild type to mutational analysis, but showed different mutations following LCM analysis. Therefore, we believed that, when primary tumoral sample results negative to mutational analysis, if it is possible, metastases should be investigated to verify the presence of mutations. Generally, it should be searched for other mutations, in addition to BRAF V600E, so as to better understand the mechanism of drug resistance.

Background: Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis.Methods: In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD.Results: In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97).Conclusions: we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures.

Previous reports highlighted the efficacy of SARS-CoV-2 specific monoclonal antibodies (mAbs) against COVID-19. Here we conducted a prospective study on clinical outcome and antiviral effect of mAbs added to standard of care therapy in SARS-CoV-2 infected patients with Primary Antibody Defects. Median time of SARS-CoV-2 qPCR positivity was shorter in eight patients treated with mAbs (22 days) than in ten patients treated with standard of care therapy only (37 days, p=0.026). Median time of SARS-CoV-2 qPCR positivity from mAbs administration was 10 days. SARS-CoV-2 mAbs treatment was effective and well-tolerated in patients with Primary Antibody Defects.

Patients affected by severe psoriasis have an increased prevalence of cardiovascular () diseases as documented by several studies. Heart rate variability (HRV) is a noninvasive method to evaluate the autonomic control of the sinus node. In this study, HRV analysis has been used to evaluate whether young patients with moderate cutaneous psoriasis have increased cardiovascular (CV) risk, in absence of CV comorbidities. Our data indicate an imbalance toward the sympathetic arm of the autonomic cardiac modulation. As the increase in sympathetic activity may be associated with a higher CV risk, moderate psoriasis could be considered to be an independent CV risk factor.

Purpose of reviewIn the general population, the risk of severe COVID-19 is associated with old age, male sex, hypertension, obesity and chronic diseases. Chronic lung diseases are listed as additional risk factors for hospitalization and ICU admission. The purpose of this review is to define whether chronic lung diseases, such as bronchiectasis and interstitial diseases, represent a risk for a severe SARS-CoV-2 infection in patients affected by common variable immunodeficiency (CVID), the most common symptomatic primary antibody defect. Recent findingsCVID patients with SARS-CoV-2 infection have been reported since the beginning of the pandemic with a wide range of clinical presentations ranging from asymptomatic to mild/moderate and severe COVID-19. The meta-analysis of 88 CVID cases described in large cohorts and case reports demonstrated that CVID patients with chronic lung involvement have an increased risk for severe COVID-19 in comparison to CVID without lung diseases (50 vs. 28%, relative risk 1.75, 95% confidence interval 1.04-2.92, P ¼ 0.043). Differently from the general population, age and metabolic comorbidities did not represent a risk factor for severe course in this patient's population.

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients.

Purpose To investigate common and uncommon CT findings in GL-ILD that may be also helpful in differential diagnosis, i.e. with sarcoidosis. To compare CT features with functional and immunological parameters. To look for radiological and non-radiological elements that may be predictive of GL-ILD therapy. Methods We retrospectively described CT features of 38 GL-ILD patients before any specific therapy. Correlations with functional and immunological features were computed. A logistic regression was performed to find a model associated with subsequent GL-ILD therapeutic decisions. Results Most common CT alterations were: bronchiectasis, non-perilymphatic nodules, consolidations, GGO, bands and enlarged mediastinal lymphnodes without calcification. GL-ILD was usually predominant in lower fields. Fibrotic ILD, GGO, reticulations and bronchiectasis were associated with decreased lung performance (p<0.05). Fibrosis, GGO and bronchiectasis were associated with low IgA levels at diagnosis, whereas high CD4+ T cells percentage was related to GGO (p<0.05). 20/38 patients underwent GL-ILD therapy after CT. A multivariate model combining MZ B cells percentage, IgA at diagnosis, CT evidence of lower field consolidations and mediastinal lymphnodes enlargement showed a good discriminatory capacity with regards to GL-ILD treatment (AUC=0.91). Conclusions Most common CT findings in GL-ILD before treatment were small nodules with a non-perilymphatic distribution, consolidations, GGO, bands and bronchiectasis. GL-ILD was usually prevalent in lower fields. A lower fields involvement with non-perylimphatic nodules and a non-traction bronchiectasis pattern could suggest GL-ILD instead of sarcoidosis. MZ B cells percentage, IgA at diagnosis, lower field consolidations and mediastinal lymphnodes enlargement were predictive of a specific GL-ILD therapy.