Recent evidence suggests that there is a link between the gut microbial community and immune-mediated disorders. Systemic sclerosis (SSc) is an autoimmune disease characterized by immunonological abnormalities, vascular lesions, and extensive fibrosis. Since the gastrointestinal tract is one of the organs most involved, the goal of this study was to explore the composition of the intestinal microbiota in SSc patients with (SSc/GI+) and without gastrointestinal involvement (SSc/GI-) in comparison to healthy controls (HC). The fecal bacterial composition was investigated by Illumina sequencing of 16 S rRNA gene amplicons. The fecal microbiota of SSc/GI+ subjects was characterized by higher levels of Lactobacillus, Eubacterium and Acinetobacter compared with healthy controls, and lower proportions of Roseburia, Clostridium, and Ruminococcus. The gut microbiota of SSc/GI- subjects was more similar to the microbiota of HC than to that of SSc/GI+ subjects albeit Streptococcus salivarius was over-represented in SSc/GI- fecal samples compared with both SSc/GI+ subjects and controls. Our study reveals microbial signatures of dysbiosis in the gut microbiota of SSc patients that are associated with clinical evidence of gastrointestinal disease. Further studies are needed to elucidate the potential role of these perturbations in the onset and progression of systemic sclerosis, and gastrointestinal involvement in particular.

BackgroundCastleman-Kojima disease (TAFRO Syndrome) is characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and histopathology pattern of atypical Castleman’s disease (CD). Only few cases of this recently identified unique variant of Multicentric CD (MCD) are described in literature, all Japanese. It therefore poses serious diagnostic and therapeutic challenges.Case descriptionWe describe a 21 year old woman with fever, asthenia, bilateral pleural effusion, ascites, hypoalbuminemia, severe thrombocytopenia, anemia, renal failure and proteinuria, whereas microbiological tests, immune serology (except ANA) and bone marrow biopsy were all negative. A CT-scan showed multiple lymphadenopathy and tissue samplings of mediastinal lymph nodes was compatible with a mixed-type CD. The diagnosis of MCD with TAFRO syndrome was made, but after an initial improvement with high dose corticosteroid therapy, clinical and laboratory features worsened. Based upon the high serum IL-6 levels and the high number of CD20-lymphocytes in lymph nodes tissue, we started tocilizumab (partial benefit), followed by rituximab combined with CVP (cyclophosphamide, vincristine and prednisone) chemotherapy, achieving a complete response. A total of six cycles of R-CVP were administered monthly, followed by maintenance with monthly rituximab. A complete remission persists at the 12th month of follow-up.ConclusionsIn patients with massive immune system activation and lymphadenopathy it is mandatory to rule out Castleman-Kojima disease. In our patient a therapy aimed at the prominent pathophysiological abnormalities has been successful so far. However, since the rarity of TAFRO Syndrome, a multicenter registry is strongly desirable for a better understanding of the disease mechanisms, hopefully leading to evidence-based therapeutic choices.

Nephrogenic adenoma is a benign lesion that may occur at any site of the genitourinary tract, usually in association with previous urothelial injuries. Although its pathogenesis is still debated, recent studies seem to confirm its derivation from renal tubular epithelium, rather than from a metaplastic process of urothelium. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic adenocarcinoma, particularly with lesions arising in the prostatic urethra. So far, immunohistochemical stains are often needed to make such a distinction, and several markers have been proposed, often with controversial results. S100A1 is a calcium binding protein that has been recently reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms. Alpha-methylacyl-CoA racemase (AMACR), a recently identified prostate cancer marker, has also been found to be expressed in renal tubules and in some renal epithelial neoplasms. In this study, we investigated the expression of S100A1 and AMACR in 18 nephrogenic adenomas and in 100 prostatic adenocarcinomas. A strong and distinct cytoplasmic or nucleocytoplasmic staining of S100A1 was found in 17 out of 18 cases of nephrogenic adenoma (94%), but never in prostatic adenocarcinoma. In contrast, AMACR expression was detected in 14 of 18 nephrogenic adenomas (78%) and in 96 of 100 prostatic adenocarcinomas (96%). We conclude that (1) S100A1 is a specific and sensitive immunohistochemical marker to differentiate nephrogenic adenoma from prostatic adenocarcinoma; (2) AMACR immunostaining does not seem to be a useful marker in distinguishing between these 2 lesions; (3) given that both S100A1 and AMACR have been reported to be expressed in renal tubular cells and in a subset of renal cell neoplasms, our findings confirm the histogenetic relationship between nephrogenic adenoma and renal tubular epithelium.

Several human cell lines derived from primary cancer of the liver are able to grow under serum-free conditions and produce spreading and growth factors which are released into the culture medium. Since this autocrine growth under hormone-free conditions might play a basic role in malignant transformation, we studied the effect on cell replication and the presence of specific membrane receptors of epidermal growth factor (EGF) and insulin on a dedifferentiated human hepatoma cell line, named HAZZT/VGH. Our results point to a similar inhibitory effect on cell replication in the presence of both EGF and insulin, in spite of detecting different affinities of binding.Hepatitis B virus; Insulin receptor; Epidermal growth factor receptor; (Human hepatoma cell line)

Data are presented from a comparative research on expression of epidermal growth factor (EGF) receptors and response to EGF of six independently established cell lines derived from human hepatoma. These lines differ in terms of the degree of differentiation, presence of hepatitis B virus (HBV) DNA copies in integrated form and expression of HBV genes. Our results indicate differential expression of membrane EGF receptors and differential response to EGF under serumand hormone-free culture conditions. Furthermore, a significant difference in affinity could be detected between EGF receptors of the two highly dedifferentiated cell lines (HA22T/VGH and Li7A) whose replication is inhibited by EGF concentrations capable of stimulating more differentiated phenotypes.Epidermal growth factor receptor; Cell replication; (Human hepatoma cell)