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Inate immunity in rosacea. Langerhans cells, plasmacytoid dentritic cells, Toll-like receptors and inducible oxide nitric synthase (iNOS) expression in skin specimens: case-control study.

Rosacea is a chronic inflammatory condition with predominant facial involvement. Because of that, many patients sense that rosacea affects quality of life. The etiology of rosacea remains unknown. Recent studies have suggested that aberrant innate immunity is central to this disease. The aim of this study was to examine the presence of Langerhans cells, plasmacytoid dentritic cells (PDC), the expression of Toll-like receptors (TLR) and inducible oxide nitric synthase (iNOS) in skin of patients with rosacea, to highlight the participation of innate immunity in its pathogenesis. 28 biopsy specimens were taken from patients with clinical and histopathological findings of rosacea. Immunohistochemical demonstration of Langerhans cells (anti-CD1a antibody), PDC (anti-CD 123 antibody), TLR2, TLR4 and iNOS was performed in skin samples and compared with normal skin controls. The expression of Langerhans cells was lower in rosacea group than in control group. PDC were found in skin samples of rosacea as isolated cells and forming small clusters. Expression of TLR2, TLR4 and iNOS was higher in rosacea samples than in normal skin controls. This research demonstrates early and late stage components of innate immunity in specimens of rosacea ratifying the existence of an altered innate immunity in its pathogenesis.

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Ninety-year-old man with hypereosinophilia, lymphadenopathies and pruritus.

We report a case of a 90-year-old man with hypereosinophilia, lymphadenopathies and skin lesions, namely lichenification and pruritus. An aetiological investigation was performed, and a bone marrow (BM) biopsy and aspirate showed a hypercellular marrow with hypereosinophilia without dysmorphia or abnormal elements, and the BM and inguinal node's immunophenotyping denied any presence of abnormal lymphoid cell population. The inguinal node biopsy revealed a multinodular proliferation of large cells S100 and CD1a+, and a diagnosis of Langerhans cell histiocytosis was made. The hypereosinophilia and skin lesions were managed with corticotherapy with substantial improvement of cutaneous lesions and lymphadenopathies and normalisation of eosinophil count. Finally, to define if it is a single or multisystem disease, a skin biopsy will be necessary.

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CD1A and CD1E gene polymorphisms are not associated with susceptibility to Guillain-Barré syndrome in the Bangladeshi population.

The post-infectious autoimmune polyradiculoneuropathy Guillain-Barré syndrome (GBS) is triggered by molecular mimicry between microbial glycolipid antigens and human peripheral nerve gangliosides. Single nucleotide polymorphisms in exon 2 of CD1A (*01/*02) and CD1E (*01/*02) were assessed using PCR-RFLP; no significant differences in genotype or allele frequency were observed between 200 patients with GBS and 200 healthy controls. CD1 gene polymorphisms cannot be recognized as a susceptibility or disease-causative factor for GBS in the Bangladeshi population. However, further studies are necessary to investigate the CD1A*01/CD1E*01 haplotype distribution and its potential causative role in the axonal form of GBS.

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Design and validation of a disease network of inflammatory processes in the NSG-UC mouse model.

Ulcerative colitis (UC) is a highly progressive inflammatory disease that requires the interaction of epithelial, immune, endothelial and muscle cells and fibroblasts. Previous studies suggested two inflammatory conditions in UC-patients: 'acute' and 'remodeling' and that the design of a disease network might improve the understanding of the inflammatory processes. The objective of the study was to design and validate a disease network in the NOD-SCID IL2rγnull (NSG)-UC mouse model to get a better understanding of the inflammatory processes.

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Erdheim-Chester Disease Involving Lymph Nodes and Liver Clinically Mimicking Lymphoma: A Case Report.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis and multisystem disease. First described in 1930, there are no more than 750 cases reported. The etiology remains unknown, but a majority of cases of ECD and Langerhans cell histiocytosis were found to have clonal mutations involving genes of the MAPK pathway. We recently encountered a 53-year-old male patient with extensive ECD involving the systemic lymph nodes, pleura, liver, and long bones clinically mimicking malignant lymphoma. Biopsies were performed at multiple sites, including a pleural mass, an external iliac lymph node, bone marrow, and the liver. Based on histopathological and immunohistochemical findings of positivity for CD68 and negativity for CD1a and S-100, the patient was diagnosed with ECD. Interferon-α was administered as the first-line treatment, but the patient rapidly progressed to hepatic failure after 2 months of treatment. We report this rare case of ECD clinically mimicking malignant lymphoma and diagnosed by careful pathological review.

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CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention.

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Advances in the understanding and management of T-cell prolymphocytic leukemia.

T-prolymphocytic leukemia (T-PLL) is a rare T-cell neoplasm with an aggressive clinical course. Leukemic T-cells exhibit a post-thymic T-cell phenotype (Tdt-, CD1a-, CD5+, CD2+ and CD7+) and are generally CD4+/CD8-, but CD4+/CD8+ or CD8+/CD4- T-PLL have also been reported. The hallmark of T-PLL is the rearrangement of chromosome 14 involving genes for the subunits of the T-cell receptor (TCR) complex, leading to overexpression of the proto-oncogene TCL1. In addition, molecular analysis shows that T-PLL exhibits substantial mutational activation of the IL2RG-JAK1-JAK3-, STAT5B axis. T-PLL patients have a poor prognosis, due to a poor response to conventional chemotherapy. Monoclonal antibody therapy with antiCD52-alemtuzumab has considerably improved outcomes, but the responses to treatment are transient; hence, patients who achieve a response to therapy are considered for stem cell transplantation (SCT). This combined approach has extended the median survival to four years or more. Nevertheless, new approaches using well-tolerated therapies that target growth and survival signals are needed for most patients unable to receive intensive chemotherapy.

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Pulmonary Langerhans cell histiocytosis in a 26-year-old female: still a diagnostic challenge.

Langerhans cell histiocytosis (LCH) is a rare disorder caused by monoclonal Langerhans cells proliferation in bone, skin, lung, lymph nodes, liver, spleen, nervous or hematopoietic system. Pulmonary LCH is a diagnostic trap that is displayed on computed tomography (CT) as an interstitial disorder with honeycomb aspect. In this paper, we present an unusual case of a 26-year-old female that was hospitalized with progressive worsening dyspnea and history of recurrent pneumonia. Lung biopsy showed fibrosis of the interalveolar septa, architectural distortion and large cells with foamy cytoplasm and convoluted nuclei that were marked by CD68, S-100 and the specific antibody CD1a that allowed establishing the diagnosis of pulmonary LCH. The only extrapulmonary manifestations were femoral bone cysts that were radiologically seen 10 years before and were not modified along the years. The therapy consisted on smoking cessation and oral corticosteroids without significant improvement of the clinical symptoms and enlargement of the cystic spaces during six months of follow-up. This case highlights for a rare disorder of the lung that should be taken into account in young patients with progressive pulmonary fibrosis.

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Primary pulmonary extranodal NK/T-cell lymphoma of nasal type misdiagnosed as pneumonia: A case report and literature review.

Primary pulmonary NK/T cell lymphoma is extremely rare, and only a few cases have reported so far. Its diagnosis is mainly dependent on open-lung biopsy.

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[Clinicopathologic analysis of micronodular thymoma with lymphoid stroma].

Objective: To investigate the clinicopathologic features of micronodular thymoma with lymphoid stroma(MNT). Methods: Five cases of MNT diagnosed from January 2007 to December 2016 in Henan Provincial People's Hospital were collected.Hematoxylin-Eosin staining and immunohistochemistry were used to evaluate the histological and immunophenotypic characteristics in 5 MNT cases. Epstein-Barr virus (EBV) status was detected by in situ hybridization for EBV-encoded small RNA (EBER). Polymerase chain reaction was used to detect the rearrangement of immunoglobulin genes. Results: Five cases were MNT, including 3 male and 2 female patients, mean aged 59 years (from 43 to 63 years). All patients had ananterior mediastinal mass, with no myasthenia gravis and autoimmune diseases, and underwent surgical resection.Half to ten years follow-up showed no recurrence.Grossly, the tumors were solid in 4 cases, and cystic and solid in 1 case; the border was clear. Histologically, the tumors presented as a distribution of micronodules separated by abundant lymphoid stroma with prominent germinal centers. The nodules were composed of neoplastic spindle, oval cells containing bland, oval nuclei.Immunohistochemical study showed strong positivity of the tumor cells for CKpan, CK19, CK5/6 and p63. Stains for EMA, CD117, calretinin, TTF1 were negative in the tumor cells.Scattered CD3, CD1a, and TdT positive immature T lymphocytes were noted in and around tumor nodules. Many lymphocytes in the stroma, including germinal centers, were positive for CD20.The bcl-2 was also detected in lymphocytes in the stroma, mantle and marginal zone of lymphoid follicles, and in part of tumor cells. Tumor cells and lymphocytes were negative for EBER. Immunoglobulin genes rearrangement analysis showed that B lymphocytes were polyclonal. Conclusions: MNT is a rare thymoma, which occurs in the elderly and has no obvious symptom. After complete resection, the prognosis is very good. The diagnosis should be based on a combination of clinicopathologic features, and other types of thymoma should be excluded.

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