Peripheral Blood Mononuclear Cells from Women with Recurrent Abortion Exhibit an Aberrant Reaction to Release Cytokines upon the Direct Contact of Human Leukocyte Antigen-G-Expressing Cells

ObjectiveTo report 3 patients with relapsing-remitting multiple sclerosis (RRMS) showing vitiligo after treatment with alemtuzumab.MethodsRetrospective case series including flow cytometric analyses and T-cell receptor (TCR) sequencing of peripheral blood mononuclear cells.ResultsWe describe 3 cases of alemtuzumab-treated patients with RRMS developing vitiligo 52, 18, and 14 months after alemtuzumab initiation. Histopathology shows loss of epidermal pigmentation with absence of melanocytes and interface dermatitis with CD8+ T-cell infiltration. Also compatible with pathophysiologic concepts of vitiligo, peripheral blood mononuclear cells of one patient showed high proportions of CD8+ T cells with an activated (human leukocyte antigen–DR+), memory (CD45RO+), and type 1 cytokine (interferon-γ + tumor necrosis factor–α) phenotype at vitiligo onset compared to a control cohort of alemtuzumab-treated patients with RRMS (n = 30). Of note, analysis of CD8 TCR repertoire in this patient revealed a highly increased clonality and reduced repertoire diversity compared to healthy controls and treatment-naive patients with RRMS. We observed a predominance of single clones at baseline in this patient and alemtuzumab treatment did not substantially affect the proportions of most abundant clones over time.ConclusionThe 3 cases represent a detailed description of vitiligo as a T-cell-mediated secondary autoimmune disease following alemtuzumab treatment. The prevailing concept of unleashed B-cell responses might therefore not cover all facets of alemtuzumab-related secondary autoimmunity. Mechanistic studies, especially on TCR repertoire, might help clarify the underlying mechanisms.

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Durable engraftment of AMD3100-mobilized autologous and allogeneic peripheral-blood mononuclear cells in a canine transplantation model

Blood ◽

10.1182/blood-2005-05-1937 ◽

2005 ◽

Vol 106 (12) ◽

pp. 4002-4008 ◽

Cited By ~ 60

Author(s):

Lauri Burroughs ◽

Marco Mielcarek ◽

Marie-Térèse Little ◽

Gary Bridger ◽

Ron MacFarland ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Canine Model ◽

Cxcr4 Antagonist ◽

Peripheral Blood Mononuclear ◽

Leukocyte Antigen ◽

Blood Mononuclear Cells ◽

Total Body

Peripheral-blood mononuclear cells (PBMCs) mobilized with AMD3100, a CXCR4 antagonist, combined with granulocyte colony-stimulating factor (G-CSF) have reconstituted autologous hematopoiesis in cancer patients following myeloablative conditioning. The engraftment potential of PBMCs mobilized with AMD3100 alone, however, has remained unproven. We therefore studied AMD3100-mobilized PBMCs in a canine model. Four dogs received 920 cGy total body irradiation (TBI) before infusion of autologous AMD3100-mobilized PBMCs (median CD34 cell count, 3.9 × 106/kg). Neutrophil (> 0.5 × 109/L [500/μL]) and platelet (> 20 ×/109/L [> 20 000/μL]) recoveries occurred at medians of 9 (range, 7-10) days and 25 (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow function at 1 year after transplantation. To evaluate the long-term engraftment potential of AMD3100-mobilized PBMCs, 5 dogs were given 920 cGy TBI followed by infusion of AMD3100-mobilized PBMCs (median CD34 cell dose, 4.7 × 106/kg) from their dog leukocyte antigen (DLA)-identical littermates. Neutrophil and platelet recoveries occurred at medians of 8 (range, 8-10) days and 26 (range, 26-37) days, respectively, after TBI. With a median follow-up of 53 (range, 33-61) weeks, recipients' marrow function was normal, and blood-donor chimerism levels were 97% to 100%. In summary, both autologous and allogeneic AMD3100-mobilized PBMCs led to prompt and durable engraftment in dogs after 920 cGy TBI.

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Epigenome-Wide Histone Acetylation Changes in Peripheral Blood Mononuclear Cells in Patients with Type 2 Diabetes and Atherosclerotic Disease

Biomedicines ◽

10.3390/biomedicines9121908 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1908

Author(s):

Pradeep Bompada ◽

Isabel Goncalves ◽

Chuanyan Wu ◽

Rui Gao ◽

Jiangming Sun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Leukocyte ◽

Atherosclerotic Disease ◽

Epigenetic Changes ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

There is emerging evidence of an association between epigenetic modifications, glycemic control and atherosclerosis risk. In this study, we mapped genome-wide epigenetic changes in patients with type 2 diabetes (T2D) and advanced atherosclerotic disease. We performed chromatin immunoprecipitation sequencing (ChIP-seq) using a histone 3 lysine 9 acetylation (H3K9ac) mark in peripheral blood mononuclear cells from patients with atherosclerosis with T2D (n = 8) or without T2D (ND, n = 10). We mapped epigenome changes and identified 23,394 and 13,133 peaks in ND and T2D individuals, respectively. Out of all the peaks, 753 domains near the transcription start site (TSS) were unique to T2D. We found that T2D in atherosclerosis leads to an H3K9ac increase in 118, and loss in 63 genomic regions. Furthermore, we discovered an association between the genomic locations of significant H3K9ac changes with genetic variants identified in previous T2D GWAS. The transcription factor 7-like 2 (TCF7L2) rs7903146, together with several human leukocyte antigen (HLA) variants, were among the domains with the most dramatic changes of H3K9ac enrichments. Pathway analysis revealed multiple activated pathways involved in immunity, including type 1 diabetes. Our results present novel evidence on the interaction between genetics and epigenetics, as well as epigenetic changes related to immunity in patients with T2D and advanced atherosclerotic disease.

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