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Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease.

Krystkowiak P, Gaura V, Labalette M, Rialland A, Remy P, Peschanski M, Bachoud-Lévi AC - PLoS ONE (2007)

Bottom Line: Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation.There had been, up to date, no report of documented cases that could have cast a doubt on those procedures.Our results underline the need for a reconsideration of the extent of the so-called immune privilege of the brain and of the follow-up protocols of patients with intracerebral grafts.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Movement Disorders, Equipe Associée 2683, Hospital R. Salengro, Regional University Hospital, Lille, France.

ABSTRACT

Background: The brain is deemed "immunologically privileged" due to sparse professional antigen-presenting cells and lymphatic drainage, and to the blood-brain barrier. Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation. This has led over the past fifteen years to the use of either short-term or even no immunosuppression in most clinical trials with foetal neural transplant in patients with Parkinson's and Huntington's disease.

Methodology/principal findings: We report biological demonstration of alloimmunisation without signs of rejection in four grafted patients out of 13 studied during the course of a clinical trial involving fetal neural transplantation in patients with Huntington's Disease. Biological, radiological and clinical demonstration of an ongoing rejection process was observed in a fifth transplanted patient. The rejection process was, however, fully reversible under immunosuppressive treatment and graft activity recovered within six months.

Conclusions/significance: There had been, up to date, no report of documented cases that could have cast a doubt on those procedures. Our results underline the need for a reconsideration of the extent of the so-called immune privilege of the brain and of the follow-up protocols of patients with intracerebral grafts. It also suggests that some of the results obtained in past studies with foetal neural transplants may have been biased by an unrecognized immune response to donor cells.

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Brain imaging of the rejection process in patient 3 and its reversion under treatment.Magnetic resonance imaging and metabolic activity using 18F-deoxyglucose before surgery (T0), during the rejection process (T1) and after 6 months of reinstated immunosuppressive treatment (T2) are shown separately (upper and middle panel, respectively), then co-registered (lower panel). The white arrow indicates the right striatum. The false colour scale shows levels of metabolic activities from lowest (min) to highest (max).
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pone-0000166-g001: Brain imaging of the rejection process in patient 3 and its reversion under treatment.Magnetic resonance imaging and metabolic activity using 18F-deoxyglucose before surgery (T0), during the rejection process (T1) and after 6 months of reinstated immunosuppressive treatment (T2) are shown separately (upper and middle panel, respectively), then co-registered (lower panel). The white arrow indicates the right striatum. The false colour scale shows levels of metabolic activities from lowest (min) to highest (max).

Mentions: Fourteen months after grafting, one patient (patient 3) started to exhibit general alteration of clinical status with weight loss of 22 kg over three months, worsened choreic movements lateralised to the left side, gait disorders and falls. Brain MRI showed an ongoing encephalitic process with vasogenic oedema, extending from the striatum to the frontal cortex mostly on the right side (Figure 1). Positron emission tomography with 18F-deoxyglucose revealed decreased metabolic activity in the same area of the right hemisphere (Figure 1), whereas striatal metabolism increased by about 50% on the left side, as commonly observed in the presence of functional grafts [3], [4].


Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease.

Krystkowiak P, Gaura V, Labalette M, Rialland A, Remy P, Peschanski M, Bachoud-Lévi AC - PLoS ONE (2007)

Brain imaging of the rejection process in patient 3 and its reversion under treatment.Magnetic resonance imaging and metabolic activity using 18F-deoxyglucose before surgery (T0), during the rejection process (T1) and after 6 months of reinstated immunosuppressive treatment (T2) are shown separately (upper and middle panel, respectively), then co-registered (lower panel). The white arrow indicates the right striatum. The false colour scale shows levels of metabolic activities from lowest (min) to highest (max).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1764859&req=5

pone-0000166-g001: Brain imaging of the rejection process in patient 3 and its reversion under treatment.Magnetic resonance imaging and metabolic activity using 18F-deoxyglucose before surgery (T0), during the rejection process (T1) and after 6 months of reinstated immunosuppressive treatment (T2) are shown separately (upper and middle panel, respectively), then co-registered (lower panel). The white arrow indicates the right striatum. The false colour scale shows levels of metabolic activities from lowest (min) to highest (max).
Mentions: Fourteen months after grafting, one patient (patient 3) started to exhibit general alteration of clinical status with weight loss of 22 kg over three months, worsened choreic movements lateralised to the left side, gait disorders and falls. Brain MRI showed an ongoing encephalitic process with vasogenic oedema, extending from the striatum to the frontal cortex mostly on the right side (Figure 1). Positron emission tomography with 18F-deoxyglucose revealed decreased metabolic activity in the same area of the right hemisphere (Figure 1), whereas striatal metabolism increased by about 50% on the left side, as commonly observed in the presence of functional grafts [3], [4].

Bottom Line: Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation.There had been, up to date, no report of documented cases that could have cast a doubt on those procedures.Our results underline the need for a reconsideration of the extent of the so-called immune privilege of the brain and of the follow-up protocols of patients with intracerebral grafts.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Movement Disorders, Equipe Associée 2683, Hospital R. Salengro, Regional University Hospital, Lille, France.

ABSTRACT

Background: The brain is deemed "immunologically privileged" due to sparse professional antigen-presenting cells and lymphatic drainage, and to the blood-brain barrier. Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation. This has led over the past fifteen years to the use of either short-term or even no immunosuppression in most clinical trials with foetal neural transplant in patients with Parkinson's and Huntington's disease.

Methodology/principal findings: We report biological demonstration of alloimmunisation without signs of rejection in four grafted patients out of 13 studied during the course of a clinical trial involving fetal neural transplantation in patients with Huntington's Disease. Biological, radiological and clinical demonstration of an ongoing rejection process was observed in a fifth transplanted patient. The rejection process was, however, fully reversible under immunosuppressive treatment and graft activity recovered within six months.

Conclusions/significance: There had been, up to date, no report of documented cases that could have cast a doubt on those procedures. Our results underline the need for a reconsideration of the extent of the so-called immune privilege of the brain and of the follow-up protocols of patients with intracerebral grafts. It also suggests that some of the results obtained in past studies with foetal neural transplants may have been biased by an unrecognized immune response to donor cells.

Show MeSH
Related in: MedlinePlus