SANI definition of Clinical Remission in Severe Asthma: a Delphi consensus

: Severe Asthma affects about 10% of the asthmatic population, and it is characterized by a low lung function and a higher count of blood leucocytes, mainly eosinophils. To date, various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. The aim of this work is to highlight a consensus for asthma remission using a Delphi method. In the context of SANI (Severe Asthma Network Italy), accounting for 57 Severe Asthma Centers and more then 2200 patients, a Board of six expert drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. 32 statements have been included in the R1 questionnaire, and then submitted to a panel of 80 experts, which used a 5-points Likert scale to measure their agreement to each statement. Then, an Interim Analysis of R1 data have been performed, items were discussed and considered to produce a consistent questionnaire for the round 2 (R2) of the analysis. After this, the Board set the R2 questionnaire, which included only the important key topics. Panelists have been asked to vote the statements in the R2 questionnaire afterwards. During R2, the criteria of complete clinical remission (the absence of need for OCS, symptoms, exacerbations/attacks, and a pulmonary function stability) and those of partial clinical remission (the absence of need for OCS, and 2 out of 3 criteria: the absence of symptoms, exacerbations/attacks, and a pulmonary stability) were confirmed. This SANI Delphi Analysis defined a valuable, independent and easy to use tool to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry

CD4:CD8 ratio and HIV infection: The 'tap-and-drain' hypothesis

The balance of CD4+ and CD8+ T cells in humans is controlled by a major autosomal gene. Here, Alberto Amadori and colleagues propose that in view of the high CD4+ cell turnover during HIV infection, individuals genetically predisposed to a high CD4:CD8 ratio can withstand HIV-associated CD4+ cell losses better than those predisposed to a low ratio

Coding potential of the X region of the human T-Cell leukemia/lymphotropic virus type II.

IF=3.90

Spontaneous Invitro Production of Virus-specific Antibody By Lymphocytes From Hiv-infected Subjects

In vitro synthesis of IgG directed against HIV components was detected by ELISA and Western blot assay of lymphocyte culture supernatants. Lymphocytes from HIV-infected individuals spontaneously produced antibody against HIV proteins very early in culture, suggesting in vivo activation of HIV-specific antibody-forming cells. The frequency of circulating B cells spontaneously secreting HIV-specific IgG was very high in some cases, but spontaneous HIV-specific antibody synthesis was not accompanied by polyclonal reactivation of B-cell clones of different specificity. The pattern of specificity of the anti-HIV antibody produced in vitro did not reflect the serum pattern consistently. These findings indicate a new approach potentially useful for the study of the immunobiology of HIV infection. The possible implications of the in vitro production of HIV-specific antibody for the diagnosis, prognosis and clinical management of this infection are also discussed

Human Monoclonal-antibody Against A Gag-coded Protein of Human Immunodeficiency Virus Produced By A Stable Ebv-transformed Cell Clone

An EBV-transformed lymphoblastoid B cell clone (A12) derived from peripheral blood lymphocytes of an HIV-1-infected individual is described. The immunoglobulin isotype produced by this clone was IgM, and Southern blot analysis of immunoglobulin gene rearrangement showed a monoclonal pattern. The A12 monoclonal antibody was specific for the p24 product of the HIV-1 gag gene. This clone is now in continuous culture for more than 8 months and no changes in its biologic properties have been observed

PROTEIN-PHOSPHORYLATION AT TYROSINE RESIDUES IN V-ABL TRANSFORMED MOUSE LYMPHOCYTES AND FIBROBLASTS

Phosphotyrosine antibodies were employed to immunodecorate and immunoprecipitate proteins phosphorylated at tyrosine residues in cells transformed by Abelson murine leukemia virus (A-MuLV). In pre-B and pre-T lymphoma cells transformed by A-MuLV, the major phosphotyrosine-containing protein has an MW of 160 kDa and shares immunologically detectable sequences with the v-abl oncogene product. Moreover, two different proteins of approximately 100 and 68 kDa, heavily phosphorylated at tyrosine, were identified. Lack of immunological cross-reactivity with viral products and phosphopeptide mapping showed that the 100 and 68 kDa proteins are coded by cellular genes. Phosphoproteins were undetectable in control resting lymphocytes. The 68 and the 100 kDa proteins were phosphorylated to different extents in proliferating lymphocytes, either stimulated by the growth factor IL-2, or transformed by M-MuLV (lacking the oncogene coded kinase). In fibroblasts transformed by A-MuLV, phosphotyrosine antibodies identified 2 proteins of 120 and 70 kDa. By immunological cross-reaction and by phosphopeptide mapping, the first was identified as a 120 kDa form of the v-abl coded kinase. The 70 kDa protein is coded by a cellular gene, is not structurally related to the 120 kDa v-abl kinase, and is different from any phosphotyrosine-containing protein detected in A-MuLV-transformed lymphocytes. These data show that, upon v-ablinduced transformation, phosphorylation at tyrosine takes place also on proteins other than the 160 or 120-kDa oncogene products. In lymphocytes and fibroblasts these proteins are different, suggesting that the cascade of events triggered by the v-abl gene in different cell types involves tyrosine phosphorylation of different specific proteins

Neopterin production in SCID mice injected with human peripheral blood mononuclear cells

Intraperitoneal transfer of peripheral blood mononuclear cells (PBMC) from human EBV+ donors into severe combined immunodeficiency (SCID) mice is a suitable model for studying some aspects of lymphomagenesis and immune activation. Neopterin is a soluble immune marker which was found to be a useful indicator for immune activation processes in humans, e.g. to monitor immunological complications in allograft recipients or to predict prognosis in HIV-infected individuals. In contrast, this pteridine compound is normally synthesized in murine organism in only very low amounts. The measurement of neopterin concentrations in serum and urine should be feasible in SCID mice reconstituted with human PBMC. In this study, we examined the usability of this experimental model for monitoring human T cell activation by neopterin measurements. The production of neopterin by SCID mice after injection of freshly isolated human PBMC, purified B or T cells and cultured Epstein-Barr virus (EBV)+ lymphoblastoid cells (LCL) was determined. It was found that neopterin can be detected early after injecting SCID mice with PBMC, whereas injection of purified human T or B cells did not result in neopterin production. Highest neopterin levels were detected in mice treated with LCL cells when developing lymphoma. We discuss the possible sources of neopterin along this process and its usefulness in this model

Cd4 Modulation and Inhibition of Hiv-1 Infectivity Induced By Monosialoganglioside Gm1 Invitro

The addition of monosialoganglioside GM1 to serum-free culture medium efficiently and specifically inhibited CD4 antigen expression on normal T lymphocytes from peripheral blood or thymus as well as on cells from H9 and Molt-3 lines; other molecules such as CD3, CD2 and CD8 were not affected. Subsequent addition of fetal calf serum or bovine and human serum albumin blocked GM1 action on CD4 expression, most likely through the formation of ganglioside-albumin complexes. Removal of GM1 from the medium was followed by the prompt reappearance of CD4 on the cell surface. GM1 treatment of H9 and Molt-3 cells greatly reduced HIV-1 infectivity, which was evaluated by reverse transcriptase activity levels in culture supernatants and p24 detection on target cells. GM1 also inhibited syncytial formation in Molt-3 cells even when treatment was initiated 24h after infection. The GM1 effect on HIV-1 infectivity, however, was not long-lasting since removal of the compound was followed by a rapid increase in viral replication, probably due to CD4 re-expression and HIV-1 propagation from a few initially infected cells