Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e. ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.

As an alternative to lifelong insulin supplementation, potentiation of immune tolerance in patients with type 1 diabetes could prevent the autoimmune destruction of pancreatic islet β-cells. This study was aimed to assess whether the G3c monoclonal antibody (mAb), which triggers the glucocorticoid-induced TNFR-related (Gitr) costimulatory receptor, promotes the expansion of regulatory T cells (Tregs) in SV129 (wild-type) and diabetic-prone NOD mice. The delivery of the G3c mAb via G3C hybridoma cells enveloped in alginate-based microcapsules (G3C/cps) for 3 weeks induced Foxp3⁺ Treg-cell expansion in the spleen of wild-type mice but not in Gitr^–/– mice. G3C/cps also induced the expansion of nonconventional Cd4⁺Cd25^–/lowFoxp3^lowGitr^int/high (GITR single-positive [sp]) Tregs. Both Cd4⁺Cd25⁺Gitr^highFoxp3⁺ and GITRsp Tregs (including also antigen-specific cells) were expanded in the spleen and pancreas of G3C/cps-treated NOD mice, and the number of intact islets was higher in G3C/cps-treated than in empty cps-treated and untreated animals. Consequently, all but two G3C/cps-treated mice did not develop diabetes and all but one survived until the end of the 24-week study. In conclusion, long-term Gitr triggering induces Treg expansion, thereby delaying/preventing diabetes development in NOD mice. This therapeutic approach may have promising clinical potential for the treatment of inflammatory and autoimmune diseases.

Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.

The star of 'This Is England' talks to Annie Lord about the misrepresentation of working-class people on TV, the return of his show 'Brassic', and his struggles with medication for a bipolar disorder

The Department of Justice has reached a settlement that will require GrafTech International Ltd., a major producer of graphite electrodes, to make significant modifications to its supply agreement with ConocoPhillips Company, along with reporting and firewall obligations, in order to proceed with its proposed acquisition of Seadrift Coke LP.

Dr Aluvihare

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Blog written for the OECD Integrity Forum 2015 on “Curbing Corruption – Investing in Growth”. The Forum will expose corruption in its myriad forms, in both the public and private sectors, as part of the OECD CleanGovBiz initiative, supporting governments, business and civil society to build integrity and fight corruption.

The judicial inquiry into alleged graft under the presidency of Jacob Zuma is laying bare the divisions of the ruling ANC. Gideon Rachman discusses Mr Zuma's testimony with Joseph Cotterill in Johannesburg and David Pilling, Africa editor.

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Jessika Power is fresh out of surgery and ready for her close-up.

NEIL ASHTON AT THE MARACANA: Germany have been regarded as the best prepared team at the tournament for some time: Best players, best training ground, best coach, best everything.

The Chandy government had faced the elections under a cloud of charges from bar bribery case to solar scam

In Jahangirpur Gram Panchayat of Bihar’s Kishanganj district, Rs 30 lakh meant for pregnant Muslim women had already been misappropriated, when a community-driven project launched by Oxfam decided to tackle the corruption head on. Ajitha Menon reports.

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Dewey Library - K5261.F76 2019