The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH). Method and materialsWe analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy). ResultsAnalysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D' = 0.92 vs D' = 0.50 respectively; P = 1.3x10(-8)). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 - 17.4) U/mL vs 21.3 (16.5 - 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 - 44.8) U/mL vs 8.8 (6.1 - 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies. ConclusionThis study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1

Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection

Background: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. Conclusions: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection

Pathology reporting in neuroendocrine neoplasms of the digestive system: everything you always wanted to know but were too afraid to ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

Formazione, selezione e valutazione della performance: il caso Adecco

Questo lavoro analizza la gestione delle risorse umane interna all’Agenzia per il lavoro Adecco Italia S.p.A., e, in particolare, delle politiche relative al ruolo del Consultant. Le caratteristiche della posizione vengono descritte tramite il modello proposto da Baron e Kreps (1999), che definisce le proprietà di coerenza o complementarità del sistema gestione risorse umane in relazione all’ambiente esterno e alle interazioni interne tra gli elementi del sistema. L’analisi ha riscontrato due incoerenze interne: tra formazione del personale e selezione e tra formazione del personale e valutazione della performance. I processi di training dei nuovi Consultant si svolgono tramite una formazione sul campo, effettuata dal Consultant responsabile. Si tratta di un approccio legato all’attività operativa del tutor, in cui la trasmissione di conoscenze e abilità avviene attraverso osservazione e ripetizione. La formazione sul campo non prevede una definizione dei fabbisogni formativi dell’allievo, né un programma strutturato e calibrato sulle sue carenze. Non è prevista una fase di feedback e valutazione delle competenze. L’impostazione data alla formazione è incoerente con la selezione del personale, poiché i criteri di scelta utilizzati riguardano in modo primario gli aspetti motivazionali e di personalità del(lla) candidato(a), oltre che le sue esperienze pregresse. L’acquisizione di eventuali abilità o competenze mancanti è delegata alla formazione, che, nella forma in cui viene svolta, non raggiunge tale obiettivo. La formazione è inoltre incoerente con la valutazione della performance del tutor, poiché si tratta di un’attività de facto presente nelle sue responsabilità, che pur incidendo in modo negativo sull’attività operativa principale, non ha riscontro nei KPI attraverso i quali il sistema a mercato del lavoro interno determina gli avanzamenti di carriera, né sotto forma di incentivi relativi alla parte variabile della retribuzione. Le due incoerenze analizzate hanno conseguenze a livello di mancati vantaggi di coerenza del sistema, e incidono sul tasso di turnover e sulla soddisfazione lavorativa dei Consultant. Viene proposta una possibile risoluzione del problema, al fine di rendere coerente la gestione RU: l’implementazione di una formazione on-the-job pianificata, che consenta di mantenere i vantaggi del training sul campo, e allo stesso tempo, di integrare la formazione alla selezione del personale, calibrando il processo formativo sui bisogni del lavoratore, suddividendolo in fasi di crescente complessità, fino allo stadio di feedback e valutazione. Tale piano prevede una formazione propedeutica per i tutor, oltre che l’inclusione di incentivi e del riconoscimento dell’attività di insegnamento sul campo a livello di valutazione della performance