Donor specific HLA antibody in hematopoietic stem cell transplantation: Implications for donor selection.

Advances in hematopoietic stem cell transplant (HSCT) have led to changes in the approach to donor selection. Many of these new approaches result in greater HLA loci mismatching, either through the selection of haploidentical donors or permissive HLA mismatches. Although these approaches increase the potential of transplant for many patients by expanding the number of acceptable donor HLA genotypes, they add the potential barrier of donor-specific HLA antibodies (DSA).

Next-generation sequencing identifies two novel HLA class II alleles, HLA-DRB1*01:115 and HLA-DRB1*14:224.

We identified two novel HLA class II alleles by NGS, HLA-DRB1*01:115 and HLA-DRB1*14:224.

The identification of a novel HLA-B allele, HLA-B*27:05:38.

HLA-B*27:05:38 differs from HLA-B*27:05:02:01 by 2 mismatches in exon 3, resulting in 2 synonymous mutations.

Identification of a novel HLA-C allele, HLA-C*07:778, in an unrelated hematopoietic stem cell donor.

HLA-C*07:778 differs from HLA-C*07:01:01:01 by a single nonsynonymous nucleotide substitution at codon 263 (CAC→CAG).

Promotion of Primary Murine Breast Cancer Growth and Metastasis by Adipose-Derived Stem Cells Is Reduced in the Presence of Autologous Fat Graft.

Background: Cell-assisted lipotransfer involves enrichment of autologous fat with supraphysiologic numbers of adipose-derived stem cells to improve graft take. Adipose-derived stem cells have been shown to promote cancer progression, raising concerns over the safety of adipose-derived stem cells and cell-assisted lipotransfer in postoncologic breast reconstruction. The authors compared the effect of adipose-derived stem cells alone, cell-assisted lipotransfer, and conventional fat grafting on breast cancer growth and metastasis.

Ticagrelor inhibits platelet-tumor cell interactions and metastasis in human and murine breast cancer.

Activated platelets promote the proliferation and metastatic potential of cancer cells. Platelet activation is largely mediated through ADP engagement of purinergic P2Y12 receptors on platelets. We examined the potential of the reversible P2Y12 inhibitor ticagrelor, an agent used clinically to prevent cardiovascular and cerebrovascular events, to reduce tumor growth and metastasis.

Pre-transplant ATR antibodies correlate with early allograft rejection.

Studies investigating the potential pathogenic effects of non-HLA antibodies (Ab) have identified Ab against the angiotensin II type 1 receptor (ATR-Ab) as a risk factor for rejection and kidney graft loss. This study sought to validate the risk of ATR-Ab for acute rejection and to explore the role of other non-HLA Abs in this capacity. Pre- and post-transplant sera from a cohort of 101 patients (n=453 samples total) were tested for ATR-Ab and other non-HLA Ab using a commercially available ELISA kit and the Luminex platform, respectively.

Effect of Compound 21, a Selective Angiotensin II Type 2 Receptor Agonist, in a Murine Xenograft Model of Dupuytren Disease.

Background: Although surgical excision and intralesional collagenase injection are mainstays in Dupuytren disease treatment, no effective medical therapy exists for recurrent disease. Compound 21, a selective agonist of the angiotensin II type 2 receptor, has been shown to protect against fibrosis in models of myocardial infarction and stroke. The authors investigated the potential use of compound 21 in the treatment of Dupuytren disease.

The composition of ectopic lymphoid structures suggests involvement of a local immune response in cardiac allograft vasculopathy.

Background: Cardiac allograft vasculopathy (CAV) is a multifactorial pathology limiting the survival of cardiac transplants. The etiology of CAV is unclear, but antibody-mediated and cellular-mediated responses have been implicated. We, and others, have observed ectopic lymphoid structures (ELS) surrounding epicardial coronary arteries with CAV.

Antibody therapy can enhance AngiotensinII-induced myocardial fibrosis.

Background: Myocardial fibrosis is a pathological process that is characterized by disrupted regulation of extracellular matrix proteins resulting in permanent scarring of the heart tissue and eventual diastolic heart failure. Pro-fibrotic molecules including transforming growth factor-β and connective tissue growth factor are expressed early in the AngiotensinII (AngII)-induced and other models of myocardial fibrosis. As such, antibody-based therapies against these and other targets are currently under development.

Cyclosporine immunosuppression does not prevent the production of donor-specific antibody capable of mediating allograft vasculopathy.

Background: Late cardiac graft rejection, primarily mediated by allograft vasculopathy (AV), remains a major limitation to cardiac transplantation, even in the face of significant calcineurin inhibitor (CNI) immunosuppression. The role played by alloantibody in AV is unclear. Evidence that CNI immunosuppression suppresses CD4(+) T-cell function would suggest that antibody production and effector function would be severely limited in CNI-treated patients.