B-cell function in severe combined immunodeficiency after stem cell or gene therapy: A review

We retrospectively analyzed the B-cell function and leukocyte chimerism of 22 patients with severe combined immunodeficiency with B cells (B+ SCID) who survived more than 2 years after bone marrow transplantation (BMT) to determine the possible consequences of BMT procedures, leukocyte chimerism, and SCID molecular deficit on B-cell function outcome. Circulating T cells were of donor origin in all patients. In recipients of HLA-identical BMT (n = 5), monocytes were of host origin in 5 and B cells were of host origin in 4 and of mixed origin in 1. In recipients of HLA haploidentical T-cell–depleted BMT (n = 17), B cells and monocytes were of host origin in 14 and of donor origin in 3. Engraftment of B cells was found to be associated with normal B-cell function. In contrast, 10 of 18 patients with host B cells still require Ig substitution. Conditioning regimen (ie, 8 mg/kg busulfan and 200 mg/kg cyclophosphamide) was shown neither to promote B-cell and monocyte engraftment nor to affect B-cell function. Eight patients with B cells of host origin had normal B-cell function. Evidence for functional host B cells was further provided in 3 informative cases by Ig allotype determination and by the detection, in 5 studied cases, of host CD27+ memory B cells as in age-matched controls. These results strongly suggest that, in some transplanted patients, host B cells can cooperate with donor T cells to fully mature in Ig-producing cells.

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Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation

Blood ◽

10.1182/blood.v81.8.2021.2021 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2021-2030 ◽

Cited By ~ 80

Author(s):

Y Dror ◽

R Gallagher ◽

DW Wara ◽

BW Colombe ◽

A Merino ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

B Cell ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Cell Numbers ◽

B Cell Function ◽

Immunodeficiency Disease ◽

Severe Combined Immunodeficiency Disease

Abstract We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus- host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.

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270 B cell function in severe combined immunodeficiency (SCID) Following HLA-identical and haploidentical marrow transplantation

Journal of Allergy and Clinical Immunology ◽

10.1016/0091-6749(88)90504-0 ◽

1988 ◽

Vol 81 (1) ◽

pp. 235

Author(s):

R.H. Buckley ◽

S. Schiff ◽

R. Johnson ◽

S. Bigner ◽

H.D. Ochs

Keyword(s):

B Cell ◽

Marrow Transplantation ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

B Cell Function

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B-cell function in canine X-linked severe combined immunodeficiency

Veterinary Immunology and Immunopathology ◽

10.1016/s0165-2427(00)00193-8 ◽

2000 ◽

Vol 75 (1-2) ◽

pp. 121-134 ◽

Cited By ~ 11

Author(s):

Brian J Hartnett ◽

Richard L Somberg ◽

Steven Krakowka ◽

Hans D Ochs ◽

Harm HogenEsch ◽

...

Keyword(s):

B Cell ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

B Cell Function

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Reconstitution of T- and B-cell function after T-lymphocyte-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency due to adenosine deaminase deficiency

Clinical Immunology and Immunopathology ◽

10.1016/0090-1229(87)90075-4 ◽

1987 ◽

Vol 44 (3) ◽

pp. 317-320 ◽

Cited By ~ 10

Author(s):

Glenn M. Silber ◽

Jerry A. Winkelstein ◽

Robert C. Moen ◽

Sheldon D. Horowitz ◽

Michael Trigg ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

B Cell ◽

T Lymphocyte ◽

Marrow Transplantation ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Adenosine Deaminase Deficiency ◽

B Cell Function

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Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation

Blood ◽

10.1182/blood.v81.8.2021.bloodjournal8182021 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2021-2030 ◽

Cited By ~ 1

Author(s):

Y Dror ◽

R Gallagher ◽

DW Wara ◽

BW Colombe ◽

A Merino ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

B Cell ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Cell Numbers ◽

B Cell Function ◽

Immunodeficiency Disease ◽

Severe Combined Immunodeficiency Disease

We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus- host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.

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