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Acute graft-versus-host disease (aGVHD), usually developing within 100 days after hematopoietic stem cell transplantation (HSCT), is mainly attributed to donor T cell pro-inflammatory responses against mismatched host histocompatibility antigens. The persistence of increased effector T cell responses following HSCT is partially related to an altered function of T regulatory cells (Tregs) and their failure to prevent GVHD. Certain immune checkpoint molecules, such as cytotoxic T-lymphocyte antigen 4, programmed cell death protein 1 (PD1) and lymphocyte activation gene-3 (LAG3), highly expressed on Tregs, are involved in maintaining immune tolerance and preventing immune-mediated inflammation. LAG3 is a newly identified inhibitory receptor, found on most immune cells, including CD4+ and CD8+ T cells, Tregs, and dendritic cells. Previous studies have demonstrated a role of LAG3 expression on T cells in GVHD suppression. Its soluble isoform sLAG3, released from the cell membrane, has been recently reported to also contribute to enhanced immune-mediated responses in solid tumors and autoimmune diseases, such as anti-PD1-resistant melanoma, rheumatoid arthritis (RA), and ANCA-associated vasculitis. Given this evidence, the current study aimed to explore a potential role of sLAG3 in GVHD development.

Preeclampsia (PET) is a hypertensive disorder that affects 2% to 8% of pregnant women. Recent observations support the hypothesis that upregulation of placental anti-angiogenic factors are responsible for the clinical manifestations of the disease. Neuropilin-1 (NP-1) is a transmembrane protein that acts as a coreceptor for vascular endothelial growth factor and as a regulatory protein in the immune system. The aim of the study was to evaluate the expression of NP-1 in PET and normal placentas. Nineteen placental specimens from severe PET pregnancies were compared with 20 placental specimens of women with low-risk pregnancy. All the specimens underwent immunohistochemical staining with anti-human NP-1 antibody. The degree of NP-1 staining was measured both for intensity and extent. Our study demonstrated NP-1 immunoreactivity mainly in the decidual cells, the intermediate trophoblast, and the syncytiotrophoblast, particularly in the areas in the syncytial knots and shed particles. The particles were strongly NP-1 immunoreactive. The expression of NP-1 in the syncytiotrophoblast was lower in placentas of PET compared with control (P=0.017). Shedding of syncytiotrophoblast particles from placenta to maternal blood occurs in normal pregnancies and is enhanced during PET and contributes to the maternal vascular injury that characterizes PET. Our new observation that shows strong NP-1 immunoreactivity of these particles, and decreased NP1 expression in syncytiotrophoblast of PET placentas in comparison to the control group, may imply a role of NP-1 in PET.

Wilms’ tumor gene 1(WT1) was recently found to play a role in solid and hematologic malignancies and serves as a marker of prognosis and minimal residual disease in acute leukemia. WT1was also found to be involved in tumor angiogenesis. There are no data concerning the involvement of WT1in angiogenesis in lymphoproliferative tumors. The aim of this study was to explore the involvement of WT1in Hodgkin lymphoma.

Immune-mediated thrombocytopenic purpura (ITP) is recognized as a cell-specific autoimmune disorder, yet, multifactorial in origin. The development of thrombocytopenia is well proven to be mediated by both humoral (anti-platelet antibodies) and cellular (T-cell) mediated mechanisms. In some cases other autoantibodies are also induced, eg, antinuclear antibody (ANA), anti-dsDNA, and anti-cardiolipin, in addition to anti-platelet antibodies. The persistance of these autoantibodies during the course of ITP could herald future development of another autoimmune disease, eg, systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). Due to the better understanding of the pathophysiology of ITP, new novel therapies were introduced aiming to achieve long-lasting remissions. In this review we will focus on the autoimmune nature of the disease and on some of the mechanisms of action of these new therapies.

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Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune responses and have a demonstrated effect on the course of collagen induced arthritis. This study was undertaken to evaluate the role of sema3A and NP-1 in the pathogenesis of systemic lupus erythematosus (SLE) and the specific effect of sema3A on the auto-reactive properties of B cells in SLE patients.

Introduction: Angiogenesis is a necessary step in tumors progression correlating and beeing indicative of an unfavourable prognosis. Preliminary reports indicated that microvessel quantification may be useful in predicting tumors outcome. There is scant data regarding caspase-3 and vascular endothelial growth factor(VEGF) as well as the appraisal of vessel density in diffuse large B-cell lymphomas (DLBCL). These aforementioned variables are of significance in the surveillance and prognostic assessment of patients diagnosed and treated for DLBCL. The purpose of the abstract is to report our findings concerning the different biological characteristics between follicular lymphoma (FL) and DLBCL regarding angiogenesis and apoptosis. MATERIALS AND METHODS: Nodal biopsies from 40 patients suffered from DLBCL were analysed. Control group included nodal biopsies from FL(5 patients) and benign nodal hyperplasia (5 patients). Microvessel quantification was performed by immunohistochemical staining, using monoclonal antibodies against factor VIII related antigen (F8RA) and against CD34. The assessment of caspase 3 level of expression was done by using monoclonal specific antibody. We also assessed the level of expression of VEGF and Ki-67 (by using specific monoclonal antibodies, qualitatively, was done by two separate trained pathologists). The evaluation of the microvessel density (MVD) and the caspase 3 was done by using the Image analyzer" Provision". Results: All the biopsies that were included had proliferative index between 40–60%. VEGF was expressed in all DLBCL, follicular lymphoma and benign nodal hyperplasia specimens, mainly extracellulary. There was no qualitative difference in the level of VEGF expression in the various biopsies. By using the Provision analysis of the MVD, we demonstrated low level of angiogenesis in nodal DLBCL as opposed to the marked angiogenesis shown in FL and benign nodal hyperplasia. The average MVD in DLBCL specimens was 17±5, in the tumor margins 48±10, FL 55 ±10 and benign nodal hyperplasia 63±5. The morphology of the blood vessels showed diversity: while in the DLBCL the blood vessels were small and almost undeveloped, in the DLBCL tumor margins, in FL and benign nodal hyperplasia the blood vessels are fully developed, large and numerous. We assessed the apoptotic level by using anti caspase 3 antibody. Remarkable difference was demonstrated: the positive caspase-3 expressing DLBCL cells was 60±12, in the FL cells it was 6± 3, and in the benign nodal hyperplasia cells it was 2±2. Discussion: In this preliminary study different biological characteristics were observed in DLBCL as opposed to FL: as in DLBCL there is low angiogenesis and high apoptotic activity, in FL and in benign nodal hyperplasia there are high angiogenic activity and low apoptotic rate. We postulate that the high apoptotic rate in DLBCL may be linked to the low angiogenesis: probably the high rate of the cellular turnover in the tumor does not permit blood vessels formation. On the other hand, the low angiogenic activity in the tumor, may, not allow sufficient nutrients and cytokins supply to the tumor cells and thereby cause to the high apoptotic rate of the tumor cells. Anti angiogenic therapy has been introduced in the last years in hematologic malignancies. Taking into consideration the above preliminary results, it is uncertain that patients suffered from DLBCL will benefit from the anti-angiogenic compounds. Further studies and clinical trials are warranted.