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Severe Combined Immunodeficiency

Bone marrow transplantation for T−B− severe combined immunodeficiency disease in Athabascan-speaking native Americans

Bone Marrow Transplantation volume 27, pages 703–709 (2001)Cite this article

Abstract

A distinct form of autosomal recessive T−B− severe combined immunodeficiency disease occurs with a high frequency among Athabascan-speaking Native Americans (SCIDA), including Navajo and Apache Indians from the southwestern US and Dene Indians from the Canadian Northwest Territories. The SCIDA gene has been linked to markers on chromosome 10p although its identity and role in the pathogenesis of this disease are unknown. We report our experience in treating 18 Navajo and Dene children with SCIDA between 1984 and 1999; 16 underwent bone marrow transplants (BMT). All children were symptomatic within 2 months of birth, had the T−B−NK+SCID phenotype and 67% presented with oral and/or genital ulcers. Three children had evidence of maternal engraftment prior to transplant. Two children died shortly after diagnosis. Three children required more than one BMT and 12 are alive with T cell reconstitution at a median follow-up of 7 years. Three children developed normal B cell immunity, two of whom received ablative conditioning therapy with either radiation or busulfan. Three of the four children who died received therapy with either radiation or busulfan and two of eight long-term survivors who were also recipients of cytotoxic chemotherapy have failed to develop secondary teeth. These results demonstrate the efficacy of BMT in treating infants with this distinct form of SCID, although B cell reconstitution remains a problem even with HLA-matched donors. Without conditioning, T cell engraftment is likely when closely HLA-matched donors are used. With T cell depletion of haplocompatible marrow, conditioning with immunosuppressive therapy may be necessary; however, children with SCIDA who were treated with intensive immunosuppressive and myeloablative therapy had a poor outcome. Bone Marrow Transplantation (2001) 27, 703–709.

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References

  1. Murphy S, Hayward AR, Troup GM et al. Gene enrichment in an American Indian population: an excess of severe combined immunodeficiency disease Lancet 1980 2: 502–505

    Article  CAS  Google Scholar 

  2. Jones JF, Ritenbaugh CK, Spence MA, Hayward A . Severe combined immunodeficiency among the Navajo. I. Characterization of phenotypes, epidemiology, and population genetics Hum Biol 1991 63: 669–682

    CAS  PubMed  Google Scholar 

  3. Rotbart HA, Levin MJ, Jones JF et al. Noma in children with severe combined immunodeficiency J Pediatr 1986 109: 596–599

    Article  CAS  Google Scholar 

  4. Kwong PC, O'Marcaigh A, Howard R et al. Oral and genital ulceration: a unique presentation of immunodeficiency in Athabacan-speaking Native American children with severe combined immune deficiency Arch Dermatol 1999 135: 927–931

    Article  CAS  Google Scholar 

  5. Li L, Drayna D, Hu D et al. The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p Am J Hum Genet 1998 62: 136–144

    Article  CAS  Google Scholar 

  6. Moshous D, Li L, Chasseval R et al. A new gene involved in DNA double-strand break repair and V(D)J recombination is located on human chromosome 10p Hum Mol Genet 2000 9: 583–588

    Article  CAS  Google Scholar 

  7. Cowan MJ, Wara DW, Weintraub PS et al. Haploidentical bone marrow transplantation for severe combined immunodeficiency disease soybean agglutinin-negative, T-depleted marrow cells J Clin Immunol 1985 5: 370–376

    Article  CAS  Google Scholar 

  8. O'Reilly RJ, Keever CA, Small TN, Brochstein J . The use of HLA-non identical T-cell-depleted marrow transplants for correction of severe combined immunodeficiency disease Immunodef Rev 1990 1: 273–309

    Google Scholar 

  9. Fischer A, Landais P, Friedrich W et al. European experience of bone-marrow transplantation for severe combined immunodeficiency Lancet 1990 336: 850–854

    Article  CAS  Google Scholar 

  10. Buckley RH, Schiff SE, Schiff RI et al. Haploidentical bone marrow stem cell transplantation in human severe combined immunodeficiency Semin Hematol 1993 30: 92–101

    CAS  Google Scholar 

  11. Dror Y, Gallagher R, Wara DW et al. Immune reconstitution in severe combined immunodeficiency disease after lectin-treated T-cell depleted haplocompatible bone marrow transplantation Blood 1993 81: 2021–2030

    CAS  Google Scholar 

  12. Buckley RH, Schiff SE, Schiff RI et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency New Engl J Med 1999 340: 508–516

    Article  CAS  Google Scholar 

  13. Benkerrou M, Wara D, Elder M et al. B cell reconstitution after mismatched bone marrow transplantation (BMT) in vitro anti-tetanus toxoid antibody production J Clin Immunol 1994 14: 98–106

    Article  CAS  Google Scholar 

  14. Pross HF, Maroun JA . The standardization of NK cell assays for use in studies of biological response modifiers J Immunol Meth 1984 68: 235–249

    Article  CAS  Google Scholar 

  15. Halberg FE, Wara WM, Weaver KE et al. Total body irradiation and bone marrow transplantation for immunodeficiency disorders in young children J Radiother Oncol 1990 18: (Suppl. 1) 114–117

    Article  Google Scholar 

  16. Cowan M, Barley F, DeSantes K et al. Transplantation of CD34+, CD3− haplocompatible peripheral blood stem cells for children with severe combined immunodeficiency disease Blood 1997 90: 104 (Abstr.)

    Google Scholar 

  17. Horn B, Viele M, Mentzer W et al. Autoimmune hemolytic anemia in patients with SCID after T cell-depleted bonemarrow and peripheral blood stem cell transplantation Bone Marrow Transplant 1999 24: 1009–1013

    Article  CAS  Google Scholar 

  18. Kline RM, Stiehm ER, Cowan MJ . Bone marrow ‘boosts’ following T cell-depleted haploidentical bone marrow transplantation Bone Marrow Transplant 1996 17: 543–548

    CAS  PubMed  Google Scholar 

  19. Fischer A . Severe combined immunodeficiencies Immunodefic Rev 1992 3: 83–100

    CAS  PubMed  Google Scholar 

  20. Schwarz K, Gauss GH, Ludwig L et al. RAG mutations in human B cell-negative SCID Science 1996 274: 97–99

    Article  CAS  Google Scholar 

  21. Nicolas N, Moshous D, Cavazzana-Calvo M et al. A human severe combined immunodeficiency condition with increased sensitivity to ionizing radiations and impaired V(D)J rearrangements defines a new DNA recombination/repair deficiency J Exp Med 1998 188: 627–634

    Article  CAS  Google Scholar 

  22. Friedrich W . Marrow transplantation in primary immunodeficiency diseases Marrow Transplant Rev 1994 4: 71–79

    Google Scholar 

  23. Haddad E, Landais P, Friedrich W et al. Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients Blood 1998 91: 3646–3653

    CAS  PubMed  Google Scholar 

  24. Cole BO, Welbury RR, Bond E, Abinun M . Dental manifestations in severe combined immunodeficiency following bone marrow transplantation Bone Marrow Transplant 2000 25: 1007–1009

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank the physicians on the Navajo, and Dene reservations for the prompt diagnosis of SCID, the nurses and housestaff at UCSF for the care that these children received pre- and post BMT, and Helen Crouch for her administrative skills in facilitating the transfer of the patients to UCSF and coordinating their evaluations. This work was supported by grants NIH AI28339 and March of Dimes FY95–0954 and FY00-301.

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Author notes

  1. AS O'Marcaigh

    Present address: Hematology Department, Our Lady's Hospital for Sick Children, Dublin, Ireland

  2. K DeSantes

    Present address: Department of Pediatrics, University of Wisconsin, Madison, WI, USA

Authors and Affiliations

  1. Department of Pediatrics Bone Marrow Transplant Division, University of California, San Francisco, CA, USA

    AS O'Marcaigh, K DeSantes, B Horn, L Li & MJ Cowan

  2. Department of Pediatrics, Tuba City Indian Health Services, Tuba City, AZ, USA

    D Hu

  3. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

    H Pabst

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O'Marcaigh, A., DeSantes, K., Hu, D. et al. Bone marrow transplantation for T−B− severe combined immunodeficiency disease in Athabascan-speaking native Americans. Bone Marrow Transplant 27, 703–709 (2001). https://doi.org/10.1038/sj.bmt.1702831

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