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Summary: The inducible T‐cell co‐stimulator (ICOS) is a T‐cell receptor that, once bound to ICOS ligand (ICOSL) expressed on several cell types including the B‐cell lineage, plays a decisive role in adaptive immunity by regulating the interplay between B and T cells. In addition to its immunomodulatory functions, we have shown that ICOS/ICOSL signalling can inhibit the activity of osteoclasts, unveiling a novel mechanism of lymphocyte–bone cells interactions. ICOS and ICOSL can also be found as soluble forms, namely sICOS and sICOSL. Here we show that: (i) levels of sICOS and sICOSL are increased in multiple myeloma (MM) compared to monoclonal gammopathy of undetermined significance and smouldering MM; (ii) levels of sICOS and sICOSL variably correlate with several markers of tumour burden; and (iii) sICOS levels tend to be higher in Durie–Salmon stage II/III versus stage I MM and correlate with overall survival as an independent variable. Moreover, surface ICOS and ICOSL are expressed in both myeloma cells and normal plasma cells, where they probably regulate different functional stages. Finally, ICOSL triggering inhibits the migration of myeloma cell lines in vitro and the growth of ICOSL+ MOPC‐21 myeloma cells in vivo. These results suggest that ICOS and ICOSL represent novel markers and therapeutic targets for MM. [ABSTRACT FROM AUTHOR]

Although platelets are traditionally recognized for their central role in hemostasis, the presence of chemotactic factors, chemokines, adhesion molecules, and costimulatory molecules in their granules and membranes indicates that they may play an immunomodulatory role in the immune response, flanking their capacity to trigger blood coagulation and inflammation. Indeed, platelets play a role not only in the innate immune response, through the expression of Toll‐like receptors (TLRs) and release of inflammatory cytokines, but also in the adaptive immune response, through expression of key costimulatory molecules and major histocompatibility complex (MHC) molecules capable to activate T cells. Moreover, platelets release huge amounts of extracellular vesicles capable to interact with multiple immune players. The function of platelets thus extends beyond aggregation and implies a multifaceted interplay between hemostasis, inflammation, and the immune response, leading to the amplification of the body's defense processes on one hand, but also potentially degenerating into life‐threatening pathological processes on the other. This narrative review summarizes the current knowledge and the most recent updates on platelet immune functions and interactions with infectious agents, with a particular focus on their involvement in COVID‐19, whose pathogenesis involves a dysregulation of hemostatic and immune processes in which platelets may be determinant causative agents. [ABSTRACT FROM AUTHOR]

Summary: Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off‐treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO‐RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end‐point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end‐points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty‐one patients were evaluable. Primary end‐point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL‐10, IL‐4, TNF‐α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response. [ABSTRACT FROM AUTHOR]

Keywords: antibodies response; multiple myeloma; rasburicase; tumor lysis syndrome EN antibodies response multiple myeloma rasburicase tumor lysis syndrome 204 206 3 04/09/20 20200401 NES 200401 Rasburicase is a recombinant urate oxidase enzyme that rapidly metabolizes uric acid into allantoin, a more soluble and rapidly secreted metabolite.[[1], [3]] Since the rasburicase protein is derived from genetically modified I Saccharomyces cerevisiae i , it may have immunogenic properties and may elicit antibody responses in humans.[[4]] In one pivotal trial, anti-rasburicase antibodies (rasAbs) were detected in 14% of patients,[6] whereas in another trial, no antibodies were detected at day 14 after first exposure.[7] To the best of our knowledge, the clinical and functional consequences of rasAbs development are unclear, and it has not been documented whether rasAbs might inhibit the catalytic activity of the enzyme. In order to verify whether the rasAbs levels remained stable over time, rasAbs were analyzed in the patient's serum collected 1 week and 1 month after the detection of rasAbs. The patient's level of allantoin slightly decreased over time, conceivably because of uric acid reduction in the patient's serum since the resume of anti-MM therapy. [Extracted from the article]

A defective switching off of the immune response is involved in several autoimmune diseases. This switching off involves Fas-mediated apoptosis, perforin-mediated fratricide of activated lymphocytes, and the suppressive activity of regulatory T (Treg) cells. These mechanisms are altered in autoimmune lymphoproliferative syndrome that often displays autoimmune thrombocytopenia. The aim of this research was to evaluate these mechanisms in adult patients with primary immune thrombocytopenia ( ITP), compared with healthy controls. The results show that a substantial subgroup of the ITP patients displayed a defective Fas function; most of them displayed decreased Fas expression in T cells activated in vitro. Moreover, ITP patients displayed an increased frequency of rare missense variations of the PRF1 gene and decreased levels of Treg. Immunological analysis showed that levels of Interleukin ( IL)10 and IL17 were decreased and marginal zone B cells were increased. Moreover, myeloid and plasmacytoid dendritic cells were decreased in ITP patients. In conclusion, in adult ITP patients, several mechanisms involved in shutting off the immune response are defective and several immunological parameters are dysregulated; these alterations may play a role in the clinical heterogeneity of the disease. [ABSTRACT FROM AUTHOR]