Search

Editorial. Comments on the nature of the skin disease called, Schnitzler's syndrome. Comparison of the disease with the more traditional varieties of urticaria; Details of clinical signs; Laboratory findings.

Human recombinant interleukin-4 (rIL-4) was assessed for its ability to promote the proliferative response of purified human B cells co-stimulated with submitogenic concentrations of soluble F(ab′)2 fragments of anti-immunoglobulin (Ig) antibodies. The growth-promoting activity of rIL-4 was usually as potent as, or even more potent than, that of recombinant interlcukin-2 (rIL-2), and more potent than that of recombinant interferon-gamma (rIFN-γ). Preincubation with rIL-4 did not cause enhancement of the proliferative response of B cells to the subsequent addition of rIL-4 and anti-IgM antibody. In contrast, the proliferative response of B cells preincubated with anti-IgM antibody and rIL-4 was potentiated by the subsequent addition of rIL-4. The simultaneous addition of rIFN-γ and rIL-2 or rIFN-γ, and rIL-4 had an additive effect in comparison with the response induced by rIL-2 or rIL-4 alone, respectively, whereas simultaneous addition of rIL-2 and rIL-4 induced a response equal or lower than that stimulated by rIL-2 or rIL-4 alone. The addition of rIFN-γ at the beginning of culture or preincubation of B cells with rIFN-γ and anti-IgM antibody potentiated the proliferative response of B cells to the subsequent addition of either rIL-2 or rIL-4. Taken together, these data suggest that rIL-4 acts as a growth factor for activated human B cells and displays on such cells a growth-promoting activity similar to that of rIL-2. [ABSTRACT FROM AUTHOR]

Recombinant interleukin-2 (rIL-2) induced highly purified human tonsillar B cells to differentiate into immunoglobulin (Ig)-producing cells in vitro. The B-cell response was not due to rIL-2- contaminating substances, but reflected the activity of IL-2 itself, since it was inhibited by addition to the cultures of anti-TAC monoclonal antibody. The rIL-2-induced B-cell response was apparently not mediated by factors released by residual T cells present in B-cell suspensions at undetectable levels, since supernatants (SN) from unstimulated autologous T cells cultured at concentrations even much higher than those possibly contaminating B-cell suspensions did not induce any detectable Ig production. In addition, the Ig production by B cells cultured with SN prepared from high numbers of autologous T cells stimulated with rIL-2, as well as from allo-activated or mitogen-stimulated T cells, was of the same magnitude as the Ig production resulting from direct addition of rIL-2 concentrations comparable with those present in the supernatants. After centrifugation on Percoll density gradients, most of the tonsillar B cells responsive to rIL-2 were recovered in the lower density cell fraction containing a number of larger activated B cells. Moreover, B-cell enriched suspensions from peripheral blood (PB) (which usually contains a lower number of in vivo activated B cells than tonsil) showed poor or no response to rIL-2 alone, but displayed significant Ig production when rIL-2 was added to the cultures in the presence of Staphylococcus aureus Cowan I (SAC) bacteria. Taken together, these data indicate that IL-2 can directly induce differentiation into Ig-producing cells of in vivo or in vitro activated human B cells. [ABSTRACT FROM AUTHOR]

The nature of lymphocyte subsets activated by soluble and insoluble protein A (SpA) was investigated by testing the ability of human tonsil populations to form rosettes with human red blood cells coated with SpA (SpA-HRBC) and to respond in vitro to SpA. SpA coupled to Sepharose beads (SpA-Seph) and Staphylococcus aureus strain Cowan I (StaCw). Purified human I cells, which were unable to form rosettes with SpA-HRBC, were not activated by SpA-Seph or StaCw, whereas 8-cell enriched suspensions, where the number of lymphocytes forming rosettes with SpA-HRBC was significantly increased in comparison with that found in unfractionated populations, showed DNA synthesis equal to or greater than unseparated lymphocytes. In contrast, soluble SpA was unable to activate highly purified B lymphocytes in 3 day cultures and induced higher DNA synthesis in unseparated than in purified human T cells. Tonsil cell suspensions depleted in cells forming rosettes with SpA-I-IRBC synthesized significantly less DNA in the presence of SpA-Seph and lost the ability to respond to StaCw. The depletion in either IgG-bearing or IgM- and/or IgD-bearing cells induced a reduction in the response of lymphocytes to SpA-Seph and StaCw. Depletion in IgM- and/or IgD-bearing cells induced a more marked decrease in the response to StaCw than depletion in lgG-bearing lymphocytes, while the decrease of the response to SpA-Seph, induced by depletion in IgM- and/or IgD-bearing cells, was lower than that induced by depletion in lgG-bearing lymphocytes. In contrast, soluble SpA-induced proliferation was not significantly affected by depletion of cells forming rosettes with SpA-HRBC' or of IgG-bearing or IgM- and/or IgD-bearing lymphocytes. These results suggest that the mitogenicity of SpA-Seph and StaCw is due to a selective binding of insoluble SpA to components present on the membrane of either IgO- bearing or IgM- and/or IgD-bearing lymphocytes. They also indicate that the potentiation of T-cell response to soluble SpA, induced by the presence in culture of non-T cells, is not due to B lymphocytes which are able to form ,rosettes with SpA-HRBC and to respond to SpA itself when it is presented to the cells on an insoluble matrix. [ABSTRACT FROM AUTHOR]

Peripheral blood lymphocytes (PBL) from 15 of 38 patients with chronic lymphocytic leukaemia (CLL) were capable of forming rosettes with human erythrocytes coated with staphylococcal protein A (SpA-HRBC). PBE from seven patients also showed a marked proliferative response after stimulation with Staphylococcus aureus bacteria strain Cowan I (Cowan Staph). The SpA-rosetting of CLL cells was inhibited by incubation with F(ab')2 fragments of anti-immunoglobulin (Ig) antibodies. In addition, incubation with these fragments inhibited the proliferative response of leukaemic B cells to Cowan Staph. The Cowan-Staph-induced proliferation of CLL cells was also impaired by the addition of normal human IgG and human IgG F(ab')2 fragments to the cultures, whereas non-immune rabbit IgG was not inhibitory. The inhibitory activity of human IgG (ab')2 fragments was retained by a SpA-Sepharose column, and it was found in the material recovered from the same column by acid elution. These data indicate that an interaction between SpA and a structure located in the F(ab')2 region of surface Ig of different classes is responsible for either SpA-binding or the Cowan-Staph-induced proliferative response of PBL from some patients with CLL. [ABSTRACT FROM AUTHOR]

To slow down the coronavirus disease 2019 (COVID-19) pandemic an unequalled vaccination campaign was initiated. Despite proven efficacy and safety, a rare but potentially fatal complication of adenoviral-vector vaccines, called vaccine-induced immune thrombotic thrombocytopenia (VITT), has emerged the pathogenesis of which seems to be related to the development of platelet-activating anti-platelet factor 4 (PF4) antibodies. While a few studies have evaluated the incidence of anti-PF4 positivity in anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine recipients, to date no studies have assessed whether an antiplatelet immunological response develops and if this associates with platelet and blood clotting activation. We carried out a prospective study in healthy subjects who received the first dose of ChAdOx1 or Ad26.COV2.S or BNT162b2 vaccines to evaluate platelet-specific and non-specific immune response and in vivo platelet activation and blood clotting activation. Individuals receiving ChAdOx1 and, less so, Ad26.COV2.S developed with high frequency auto- or alloantiplatelet antibodies, increased circulating platelet-derived microvesicles and soluble P-selectin associated with mild blood clotting activation. Our study shows that an immunological reaction involving platelets is not uncommon in individuals receiving anti-SARS-CoV-2 vaccination, especially after ChAdOx1 and Ad26.COV2.S, and that it associates with in vivo platelet and blood clotting activation., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n = 255) and without (n = 165) skin lesions, smouldering (n = 20), aggressive (n = 28), associated with other hematological diseases mastocytosis (n = 21) and mast cell leukemia (n = 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations. Am. J. Hematol. 91:692-699, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)