Abstract

Primarily due to recent advances of detection techniques, microchimerism (the proportion of minor variant population is below 1%) has recently gained increasing attention in the field of transplantation. Availability of polymorphic markers, such as deletion insertion or single nucleotide polymorphisms along with a vast array of high sensitivity detection techniques, allow the accurate detection of small quantities of donor- or recipient-related materials. This diagnostic information can improve monitoring of allograft injuries in solid organ transplantations (SOT) as well as facilitate early detection of relapse in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present review, genetic marker and detection platform options applicable for microchimerism detection are discussed. Furthermore, current results of relevant clinical studies in the context of microchimerism and SOT or allo-HSCT respectively are also summarized.

Highlights

  • Co-existence of genetically distinct/discordant tissues or cells is termed chimerism after the well-known Greek fusion creature

  • We provide an extensive review of the available information about microchimerism in the context of various forms of transplantation and transplantation-related advanced therapies with a special emphasis on the available markers and the multitude of detection platforms in this high sensitivity range

  • The major advantage of deletion insertion polymorphisms (DIP) is the potential to use these markers in high sensitivity assay such as quantitative polymerase chain reaction (PCR) or digital PCR to reliably detect microchimerism important in solid organ transplantations (SOT) and allo-HSCT

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Summary

Introduction

Co-existence of genetically distinct/discordant tissues or cells is termed chimerism after the well-known Greek fusion creature. Based on the extent of the variant population, microchimerism is usually mentioned as a subgroup of chimerism in which the proportion of foreign cells or tissue does not exceed 1%. This proportion can readily be estimated in the circulation while quantitative comparison of major and minor populations is more challenging in cases of scattered cells or transplanted tissue. Chimerism could be investigated on cellular or on cfDNA level The latter consists mainly of small sized (around 150 base-pairs) double-stranded DNA fragments resulting from apoptosis, necrosis, immune-mediated cell damage, or release of nuclear DNA into the circulation predominantly from hematopoietic cells [2]. We provide an extensive review of the available information about microchimerism in the context of various forms of transplantation and transplantation-related advanced therapies with a special emphasis on the available markers and the multitude of detection platforms in this high sensitivity range

Polymorphic Genetic Markers Applicable for Chimerism Detection
Other Special Markers Used in Monitoring
Guidelines for Marker Selection to Detect Clinical Chimerism
Comparison of Microchimerism Detection Techniques
Role of Microchimerism in Solid Organ Transplantation
Study Design *
General Applications of Chimerism Monitoring in Allo-HSCT
Relevance of Microchimerism Monitoring in Allo-HSCT
Special Applications of Microchimerism Monitoring in Cellular Therapies
Cell-Free DNA Chimerism Following Allo-HSCT
Findings
Future Perspectives

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