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Assessment of plasma microvesicles to monitor pancreatic islet graft dysfunction: Beta cell‐ and leukocyte‐derived microvesicles as specific features in a pilot longitudinal study
Author(s) -
Amoura Lamia,
ElGhazouani Fatiha Z.,
Kassem Mohamad,
El Habhab Ali,
Kreutter Guillaume,
Sahraoui Salah,
Bosco Domenico,
Jessel Nadia,
Berney Thierry,
Benhamou PierreYves,
Toti Florence,
Kessler Laurence
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15534
Subject(s) - medicine , islet , microvesicles , lymphocyte , immunology , endocrinology , insulin , biology , microrna , biochemistry , gene
Markers of early pancreatic islet graft dysfunction and its causes are lacking. We monitored 19 type 1 diabetes islet‐transplanted patients for up to 36 months following last islet injection. Patients were categorized as Partial ( PS ) or complete (S) Success, or Graft Failure (F), using the β‐score as an indicator of graft function. F was the subset reference of maximum worsened graft outcome. To identify the immune, pancreatic, and liver contribution to the graft dysfunction, the cell origin and concentration of circulating microvesicles ( MV s) were assessed, including MV s from insulin‐secreting β‐cells typified by polysialic acid of neural cell adhesion molecule ( PSA ‐ NCAM ), and data were compared with values of the β‐score. Similar ranges of PSA ‐ NCAM + ‐ MV s were found in healthy volunteers and S patients, indicating minimal cell damage. In PS , a 2‐fold elevation in PSA ‐ NCAM + ‐ MV s preceded each β‐score drop along with a concomitant rise in insulin needs, suggesting β‐cell damage or altered function. Significant elevation of liver asialoglycoprotein receptor ( ASGPR ) + ‐ MV s, endothelial CD 105 + ‐ MV s, neutrophil CD 66b + ‐ MV s, monocyte CD 14 + ‐ MV s, and T4 lymphocyte CD 4 + ‐ MV s occurred before each β‐score drop, CD 8 + ‐ MV s increased only in F, and B lymphocyte CD 19 + ‐ MV s remained undetectable. In conclusion, PSA ‐ NCAM + ‐ MV s are noninvasive early markers of transplant dysfunction, while ASGPR + ‐ MV s signal host tissue remodeling. Leukocyte MV s could identify the cause of graft dysfunction.