Selective immunoglobulin M deficiency in an adult with miliary tuberculosis: A clinically interesting coexistence. A case report and review of the literature

AbstractSelective immunoglobulin M (SIgM) deficiency is a rare form of dysgammaglobulinemia. Here we are reporting a 31year old man with multiple cervical and testicular abscesses who was investigated and found to have miliary tuberculosis (MTB) with primary SIgM deficiency (Serum IgM: 17.4mg/dL) and was treated aggressively with anti-tuberculous treatment

Resistance of KIR ligand-missing leukocytes to natural killer cells in vivo in patients with acquired aplastic anemia

金沢大学医薬保健研究域医学系　Graduate School of Medical SciencesThe loss of killer cell immunoglobulin-like receptor-ligands (KIR-Ls) due to the copy number neutral loss of heterozygosity of chromosome 6p (6pLOH) in leukocytes of patients with acquired aplastic anemia (AA) may alter the susceptibility of the affected leukocytes to NK cell killing in vivo. We studied 408 AA patients, including 261 who were heterozygous for KIR-Ls, namely C1/C2 or Bw6/Bw4, for the presence of KIR-L-missing (KIR-L[-]) leukocytes. KIR-L(-) leukocytes were found in 14 (5.4%, C1, n= 4, C2, n=3, and Bw4, n= 7) of the 261 patients, in whom corresponding KIR(+) licensed NK cells were detected. The incidence of 6pLOH in the 261 patients (18.0%) was comparable to that in 147 patients (13.6%) who were homozygous for KIR-L genes. The percentages of HLA-lacking granulocytes (0.8-50.3%, median 15.2%) in the total granulocytes of the patients with KIR-L(-) cells were significantly lower than those (1.2-99.4%, median 55.4%) in patients without KIR-L(-) cells. KIR2DS1 and KIR3DS1 were only possessed by three of the 14 patients, two of whom had C2/C2 leukocytes after losing C1 alleles. The expression of the KIR3DS1 ligand HLA-F was selectively lost on KIR-L(-) primitive hematopoietic stem cells (HSCs) derived from 6pLOH(+) iPS cells in one of the KIR3DS1(+) patients. These findings suggest that human NK cells are able to suppress the expansion of KIR-L(-) leukocytes but are unable to eliminate them partly due to the lack of activating KIRs on NK cells and the low HLA-F expression level on HSCs in AA patients.Embargo Period 6 month

Stem cells for osteochondral regeneration

Stem cell research plays a central role in the future of medicine, which is mainly dependent on the advances on regenerative medicine (RM), specifically in the disciplines of tissue engineering (TE) and cellular therapeutics. All RM strategies depend upon the harnessing, stimulation, or guidance of endogenous developmental or repair processes in which cells have an important role. Among the most clinically challenging disorders, cartilage degeneration, which also affects subchondral bone becoming an osteochondral (OC) defect, is one of the most demanding. Although primary cells have been clinically applied, stem cells are currently seen as the promising tool of RM-related research because of its availability, in vitro proliferation ability, pluri- or multipotency, and immunosuppressive features. Being the OC unit, a transition from the bone to cartilage, mesenchymal stem cells (MSCs) are the main focus for OC regeneration. Promising alternatives, which can also be obtained from the patient or at banks and have great differentiation potential toward a wide range of specific cell types, have been reported. Still, ethical concerns and tumorigenic risk are currently under discussion and assessment. In this book chapter, we revise the existing stem cell-based approaches for engineering bone and cartilage, focusing on cell therapy and TE. Furthermore, 3D OC composites based on cell co-cultures are described. Finally, future directions and challenges still to be faced are critically discussed.H2020-MSCA-RISE program, as this work is part of developments carried out in BAMOS project, funded from the European Union's Horizon 2020 research and innovation program under grant agreement Nº 734156. Thanks are also due to the Portuguese Foundation for Science and Technology (FCT) for the distinction attributed to J. M. Oliveira (IF/00423/2012 and IF/01285/2015) and to Rogério Pirraco (IF/00347/2015) under the Investigator FCT program. The authors also thank FCT for the Ph.D. scholarship provided to R. F. Canadas (SFRH/BD/92565/2013)info:eu-repo/semantics/publishedVersio