MHC haplotype diversity in Icelandic horses determined by polymorphic microsatellites

Holmes, Camille M.; Violette, Nathaniel P.; Miller, Donald C.; Wagner, Bettina; Svansson, Vilhjálmur; Antczak, Douglas F.

doi:10.1038/s41435-019-0075-y

Cited by 17 publications

(15 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of new 22 provisional haplotypes were found in 17 animals involved in the previous in vivo study, whereas one animal could not be assigned with any haplotype. None of the haplotypes observed in this population was previously described [18,24]. Further detailed information about ELA microsatellite typing is available in Additional file 1.…”

Section: Assignation Of Ela Haplotypesmentioning

confidence: 93%

Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility

et al. 2020

View full text Add to dashboard Cite

Background Antibody production after allogeneic administration of mesenchymal stem cells (MSCs) could impact their clinical application. Proinflammatory priming of MSCs can potentiate their regulatory ability in vivo but increased expression of major histocompatibility complex (MHC) might augment their immunogenicity, potentially leading to immune memory thus limiting repeated allogeneic administration. This study aimed at evaluating the production of cytotoxic allo-antibodies directed against donor’s ELA (equine leukocyte antigen) in mismatched and halfmatched horses receiving repeated intraarticular administration of stimulated MSCs (MSC-primed) and unstimulated MSCs (MSC-naïve) in pathologic joints. Methods From available stored samples from a previous in vivo study, cells from one donor and serially collected sera (five time-points) from three groups of recipients were used based on their ELA haplotypes to perform microcytotoxicity assays: Group 1 recipients mismatched with the donor that received MSC-naïve (naïve-mismatched recipients); Group 2 recipients mismatched with the donor that received MSC-primed (primed-mismatched recipients); Group 3 recipients halfmatched with the donor (sharing 1/2 haplotypes) that received MSC-primed (primed-halfmatched recipients). Sera from recipients (neat, 1:2 and 1:16 dilution) were tested against target cells from the donor (cryopreserved and expanded MSC-naïve and MSC-primed) or from one animal presenting the same ELA haplotypes than the donor (fresh peripheral blood lymphocytes as control). Results One to three weeks after first MSC administration, all recipient groups produced allo-antibodies regardless of MSC received (naïve or primed) and matching degree with donor. However, secondary response after MSC re-exposure was less evident in halfmatched recipients (MSC-primed) than in mismatched ones (both MSC-naïve and MSC-primed). Recipients of MSC-primed (both mismatched and halfmatched) tended towards developing lower antibody response than MSC-naïve recipients in vivo, but MSC-primed were targeted to death in higher percentage in vitro in the microcytoxicity assay. Conclusions After first intraarticular allogeneic administration, the immunomodulatory profile of MSC-primed would have led to lower antibody production, but these antibodies would target more easily MSC-primed after second injection (re-exposure), likely because of their higher MHC expression.

show abstract

Section: Assignation Of Ela Haplotypesmentioning

confidence: 93%

Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility

et al. 2020

View full text Add to dashboard Cite

show abstract

“…DNA was extracted from lymphocytes using a commercially available kit (Qiagen). Genomic DNA was amplified using multiplex fluorescent polymerase chain reaction (PCR) with known primers for 12 microsatellite loci within the MHC region 32 . PCR fragments were submitted to the Cornell University BioResource Center (BRC) and electrophoresed on an ABI 3700 instrument.…”

Section: Methodsmentioning

confidence: 99%

“…Conversely, the horse has wide genetic diversity with frequent MHC recombination events and is an ideal model to study immune compatibility of allogeneic cell therapy 26‐28 . Additionally, the horse is well‐recognized for its value as a preclinical model for joint injury as the equine articular joint closely mimics that of man in the cartilage thickness and collagen distribution as well as the architecture of subchondral bone 29,30 .…”

Section: Introductionmentioning

confidence: 99%

Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting

Rowland

Miller

Berglund

et al. 2020

Stem Cells Translational Medicine

Self Cite

View full text Add to dashboard Cite

Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross‐matching, on the assumption that they are immune‐privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra‐articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri‐articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor‐specific antibodies in mismatched recipients compared with recipients receiving matched allogeneic or autologous MSCs. Importantly, in matched allogeneic and autologous recipients, but not mismatched allogeneic recipients, there was increased stromal derived factor‐1 along with increased MSC concentrations in synovial fluid. Until immune recognition of MSCs can be avoided, repeated clinical use of MSCs should be limited to autologous or cross‐matched allogeneic MSCs. When non–cross‐matched allogeneic MSCs are used in single MSC dose applications, presensitization against donor MHC should be assessed.

show abstract

“…However, MHC microsatellites are commonly used to evaluate the equine MHC, including studies where MHC compatibility between horses is of importance [ 24 – 28 ]. Unlike DNA sequencing, microsatellites are only indirect markers of MHC, but despite the above, they are regarded as reliable indicators of MHC haplotype and MHC genes sequencing [ 16 , 17 , 24 – 32 ]. However, we acknowledge that microsatellite typing could be less effective than DNA sequencing in identifying possible differences and similarities in DNA.…”

Section: Discussionmentioning

confidence: 99%

“…However, MHC microsatellite typing is a well-established method employed in research studies investigating the role of MHC in the physiology and pathology of horses [ 27 , 28 ], including the experiments where the immune response to foreign antigen is of major interest [ 24 – 26 ]. The analyzed microsatellites were found to accurately correspond to MHC haplotypes, namely the set of MHC alleles in an individual [ 16 , 17 , 29 – 32 ]. In this study, a comparison of MHC alleles in mares and foals demonstrated that MHC microsatellite typing is an effective technique.…”

Section: Discussionmentioning

confidence: 99%

Is similarity in Major Histocompatibility Complex (MHC) associated with the incidence of retained fetal membranes in draft mares? A cross-sectional study

2020

View full text Add to dashboard Cite

The failure of the maternal immune system to recognize fetal antigens and vice versa due to MHC similarity between the foal and its dam might result in the lack of placental separation during parturition in mares. The aim of the study was to investigate the influence of MHC similarity between a mare and a foal on the incidence of retained fetal membranes (RFM) in post-partum mares. DNA was sampled from 43 draft mares and their foals. Mares which failed to expel fetal membranes within three hours after foal expulsion were considered the RFM group (n = 14) and mares that expelled fetal membranes during the above period were the control group (n = 29). Nine MHC microsatellites of MHC I and MHC II were amplified for all mares and foals. MHC compatibility and MHC genetic similarity between mares and their foals was determined based on MHC microsatellites. The inbreeding coefficient was also calculated for all horses. The incidence of RFM in the studied population was 33%. Compatibility in MHC I and MHC II did not increase the risk of RFM in the studied population of draft mares (P>0.05). Differences in MHC similarity at the genetic level were not observed between mare-foal pairs in RFM and control group (P>0.05). We suspect that RFM in draft mares may not be associated with MHC similarity between a foal and its dam. Despite the above, draft horses could be genetically predisposed to the disease.

show abstract

MHC haplotype diversity in Icelandic horses determined by polymorphic microsatellites

Cited by 17 publications

References 56 publications

Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility

Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility

Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting

Is similarity in Major Histocompatibility Complex (MHC) associated with the incidence of retained fetal membranes in draft mares? A cross-sectional study

Contact Info

Product

Resources

About