scholarly journals Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 580-587 ◽  
Author(s):  
C Klein ◽  
M Cavazzana-Calvo ◽  
F Le Deist ◽  
N Jabado ◽  
M Benkerrou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Bone Marrow Transplantation ◽  
Mhc Class Ii ◽  
Marrow Transplantation ◽  
Class Ii ◽  
Combined Immunodeficiency ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Deficiency

Abstract Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome) is a rare inborn error of the immune system characterized by impaired antigen presentation and combined immunodeficiency. It causes severe and unremitting infections leading to progressive liver and lung dysfunctions and death during childhood. As in other combined immunodeficiency disorders, bone marrow transplantation (BMT) is considered the treatment of choice for MHC class II deficiency. We analyzed the files of 19 patients who have undergone BMT in our center. Of the 7 patients who underwent HLA- identical BMT, 3 died in the immediate posttransplant period of severe viral infections, whereas the remaining 4 were cured, with recovery of normal immune functions. Of the 12 patients who underwent HLA-haplo- identical BMT, 3 were cured, 1 was improved by partial engraftment, 7 died of infectious complications due to graft failure or rejection, and 1 is still immunodeficient because of engraftment failure. A favorable outcome in the HLA-non-identical BMT group was associated with an age of less than 2 years at the time of transplantation. All the patients with stable long-term engraftment had persistently low CD4 counts after transplantation (105 to 650/microL at last follow up), but no clear susceptibility to opportunistic infections despite persisting MHC class II deficiency on thymic epithelium and other nonhematopoietic cells. We conclude that HLA-identical and -haploidentical BMT can cure MHC class II deficiency, although the success rate of haploidentical BMT is lower than that in other combined immunodeficiency syndromes. HLA- haploidentical BMT should preferably be performed in the first 2 years of life, before the acquisition of chronic virus carriage and sequelae of infections.

scholarly journals Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 580-587
Author(s):  
C Klein ◽  
M Cavazzana-Calvo ◽  
F Le Deist ◽  
N Jabado ◽  
M Benkerrou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Bone Marrow Transplantation ◽  
Mhc Class Ii ◽  
Marrow Transplantation ◽  
Class Ii ◽  
Combined Immunodeficiency ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Deficiency

Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome) is a rare inborn error of the immune system characterized by impaired antigen presentation and combined immunodeficiency. It causes severe and unremitting infections leading to progressive liver and lung dysfunctions and death during childhood. As in other combined immunodeficiency disorders, bone marrow transplantation (BMT) is considered the treatment of choice for MHC class II deficiency. We analyzed the files of 19 patients who have undergone BMT in our center. Of the 7 patients who underwent HLA- identical BMT, 3 died in the immediate posttransplant period of severe viral infections, whereas the remaining 4 were cured, with recovery of normal immune functions. Of the 12 patients who underwent HLA-haplo- identical BMT, 3 were cured, 1 was improved by partial engraftment, 7 died of infectious complications due to graft failure or rejection, and 1 is still immunodeficient because of engraftment failure. A favorable outcome in the HLA-non-identical BMT group was associated with an age of less than 2 years at the time of transplantation. All the patients with stable long-term engraftment had persistently low CD4 counts after transplantation (105 to 650/microL at last follow up), but no clear susceptibility to opportunistic infections despite persisting MHC class II deficiency on thymic epithelium and other nonhematopoietic cells. We conclude that HLA-identical and -haploidentical BMT can cure MHC class II deficiency, although the success rate of haploidentical BMT is lower than that in other combined immunodeficiency syndromes. HLA- haploidentical BMT should preferably be performed in the first 2 years of life, before the acquisition of chronic virus carriage and sequelae of infections.

Incomplete T-Cell Immune Reconstitution in Two Major Histocompatibility Complex Class II–Deficiency/Bare Lymphocyte Syndrome Patients After HLA-Identical Sibling Bone Marrow Transplantation

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 348-358 ◽  
Author(s):  
Barbara C. Godthelp ◽  
Marja C.J.A. van Eggermond ◽  
Ad Peijnenburg ◽  
Ilhan Tezcan ◽  
Stefaan van Lierde ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Mhc Class Ii ◽  
Immune Reconstitution ◽  
Cd8 T Cell ◽  
Class Ii ◽  
Histocompatibility Complex

To study the effects of major histocompatibility complex (MHC) class II expression on T-cell development, we have investigated T-cell immune reconstitution in two MHC class II–deficiency patients after allogeneic bone marrow transplantation (allo-BMT). Our study showed that the induction of MHC class II antigen expression on BM graft-derived T cells in these allo-BMT recipients was hampered upon T-cell activation. This reduction was most striking in the CD8+ T-cell subset. Furthermore, the peripheral T-cell receptor (TCR) repertoire in these graft-derived MHC class II–expressing CD4+ and in the CD8+ T-cell fractions was found to be restricted on the basis of TCR complementarity determining region 3 (CDR3) size profiles. Interestingly, the T-cell immune response to tetanus toxoid (TT) was found to be comparable to that of the donor. However, when comparing recipient-derived TT-specific T cells with donor-derived T cells, differences were observed in TCR gene segment usage and in the hydropathicity index of the CDR3 regions. Together, these results reveal the impact of an environment lacking endogenous MHC class II on the development of the T-cell immune repertoire after allo-BMT.

scholarly journals Genetic evidence for a new type of major histocompatibility complex class II combined immunodeficiency characterized by a dyscoordinate regulation of HLA-D alpha and beta chains.

1996 ◽  
Vol 183 (3) ◽  
pp. 1063-1069 ◽  
Author(s):  
J Douhan ◽  
I Hauber ◽  
M M Eibl ◽  
L H Glimcher
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Lines ◽  
Mhc Class Ii ◽  
Genetic Disorder ◽  
Class Ii ◽  
Genetic Evidence ◽  
Combined Immunodeficiency ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Major histocompatibility complex (MHC) class II combined immunodeficiency (CID), also known as type II bare lymphocyte syndrome, is an autosomal recessive genetic disorder characterized by the complete lack of expression of MHC class II antigens. The defect results from a coordinated lack of transcription of all class II genes. Cell fusion studies using many patient- and experimentally derived class II-negative cell lines have identified four distinct genetic complementation groups. In this report, we present genetic evidence that cell lines derived from two newly described MHC class II-deficient patients, KER and KEN, represent a fifth complementation group. In addition, the KER and KEN cell lines display a unique pattern of dyscoordinate regulation of their MHC class II genes, which is reflected in a new phenotype of in vivo promoter occupancy as revealed by in vivo genomic footprinting. These data point to a new defect that can result in the MHC class II-deficient phenotype.

scholarly journals Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 542-547 ◽  
Author(s):  
P Mauch ◽  
JM Lipton ◽  
BL Hamilton ◽  
J Obbagy ◽  
D Nathan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Cultured Cells ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Host Disease ◽  
Murine Bone Marrow ◽  
Histocompatibility Complex

Abstract The murine bone marrow culture technique was used to prepare donor marrow for bone marrow transplantation across minor histocompatibility complex differences. Previous studies have shown that theta-positive cells are rapidly lost from such cultures and that transplantation of cultured marrow across major histocompatibility complex differences results in a delay in the development of lethal graft-v-host disease (GVHD). In this study, a total of 1 to 2 X 10(7) nonadherent cells (740 to 1560 CFUs [colony-forming units]) from three-day-old cultures were used as a source of donor marrow. Three strain combinations were evaluated; LP/J into C57BL/6; BIO.BR into CBA/J; and C57BL/6 into LP/J. Donor mice were immunized with recipient spleen cells prior to culture in order to increase the graft-v-host response. For LP/J marrow into C57BL/6 mice, 5 X 10(7) donor spleen cells transplanted along with the marrow were needed to induce lethal GVHD. However, lethal GVHD was seen without the addition of spleen cells for BIO.BR into CBA/J and C57BL/6 into LP/J strain combinations. Most animals receiving fresh marrow were dead of GVHD five weeks after transplantation. With the use of cultured marrow the three-month survival was 80%, 51%, and 93%, respectively, for LP/J into C57BL/6, BIO.BR into CBA/J, and C57BL/6 into LP/J strain combinations. Long-term donor engraftment in all recipient animals receiving cultured marrow was confirmed by analyzing hemoglobin polymorphisms between the strain combinations. These results demonstrate that in contrast to transplantation across major histocompatibility complex differences, the use of cultured cells for bone marrow transplantation across minor histocompatibility complex differences allows for engraftment while reducing the risk of lethal GVHD.

scholarly journals Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 542-547
Author(s):  
P Mauch ◽  
JM Lipton ◽  
BL Hamilton ◽  
J Obbagy ◽  
D Nathan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Cultured Cells ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Host Disease ◽  
Murine Bone Marrow ◽  
Histocompatibility Complex

The murine bone marrow culture technique was used to prepare donor marrow for bone marrow transplantation across minor histocompatibility complex differences. Previous studies have shown that theta-positive cells are rapidly lost from such cultures and that transplantation of cultured marrow across major histocompatibility complex differences results in a delay in the development of lethal graft-v-host disease (GVHD). In this study, a total of 1 to 2 X 10(7) nonadherent cells (740 to 1560 CFUs [colony-forming units]) from three-day-old cultures were used as a source of donor marrow. Three strain combinations were evaluated; LP/J into C57BL/6; BIO.BR into CBA/J; and C57BL/6 into LP/J. Donor mice were immunized with recipient spleen cells prior to culture in order to increase the graft-v-host response. For LP/J marrow into C57BL/6 mice, 5 X 10(7) donor spleen cells transplanted along with the marrow were needed to induce lethal GVHD. However, lethal GVHD was seen without the addition of spleen cells for BIO.BR into CBA/J and C57BL/6 into LP/J strain combinations. Most animals receiving fresh marrow were dead of GVHD five weeks after transplantation. With the use of cultured marrow the three-month survival was 80%, 51%, and 93%, respectively, for LP/J into C57BL/6, BIO.BR into CBA/J, and C57BL/6 into LP/J strain combinations. Long-term donor engraftment in all recipient animals receiving cultured marrow was confirmed by analyzing hemoglobin polymorphisms between the strain combinations. These results demonstrate that in contrast to transplantation across major histocompatibility complex differences, the use of cultured cells for bone marrow transplantation across minor histocompatibility complex differences allows for engraftment while reducing the risk of lethal GVHD.

Sign in / Sign up

Export Citation Format

Share Document