Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases)

Jan Storek, Zhao Zhao, Eugene Lin, Thomas Berger, Peter A. McSweeney, Richard A. Nash, Yoshiki Akatsuka, Monja D. Metcalf, Hailing Lu, Tomas Kalina, Markus Reindl, Rainer Storb, John A. Hansen, Keith M. Sullivan, George H. Kraft, Daniel E. Furst, David G. Maloney

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells.

Original languageEnglish
Pages (from-to)285-298
Number of pages14
JournalClinical Immunology
Volume113
Issue number3
DOIs
Publication statusPublished - 01-12-2004
Externally publishedYes

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Lymphopenia
Autoimmune Diseases
T-Lymphocytes
Cell Count
Antibodies
Systemic Scleroderma
Cell Transplantation
Leukopenia
CD4 Lymphocyte Count
Infection
Plasma Cells
Natural Killer Cells
Autoantibodies
Dendritic Cells
Multiple Sclerosis
Monocytes
Immunity
Neutrophils
B-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Storek, J., Zhao, Z., Lin, E., Berger, T., McSweeney, P. A., Nash, R. A., ... Maloney, D. G. (2004). Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). Clinical Immunology, 113(3), 285-298. https://doi.org/10.1016/j.clim.2004.07.006
Storek, Jan ; Zhao, Zhao ; Lin, Eugene ; Berger, Thomas ; McSweeney, Peter A. ; Nash, Richard A. ; Akatsuka, Yoshiki ; Metcalf, Monja D. ; Lu, Hailing ; Kalina, Tomas ; Reindl, Markus ; Storb, Rainer ; Hansen, John A. ; Sullivan, Keith M. ; Kraft, George H. ; Furst, Daniel E. ; Maloney, David G. / Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). In: Clinical Immunology. 2004 ; Vol. 113, No. 3. pp. 285-298.
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Storek, J, Zhao, Z, Lin, E, Berger, T, McSweeney, PA, Nash, RA, Akatsuka, Y, Metcalf, MD, Lu, H, Kalina, T, Reindl, M, Storb, R, Hansen, JA, Sullivan, KM, Kraft, GH, Furst, DE & Maloney, DG 2004, 'Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases)', Clinical Immunology, vol. 113, no. 3, pp. 285-298. https://doi.org/10.1016/j.clim.2004.07.006

Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). / Storek, Jan; Zhao, Zhao; Lin, Eugene; Berger, Thomas; McSweeney, Peter A.; Nash, Richard A.; Akatsuka, Yoshiki; Metcalf, Monja D.; Lu, Hailing; Kalina, Tomas; Reindl, Markus; Storb, Rainer; Hansen, John A.; Sullivan, Keith M.; Kraft, George H.; Furst, Daniel E.; Maloney, David G.

In: Clinical Immunology, Vol. 113, No. 3, 01.12.2004, p. 285-298.

Research output: Contribution to journalArticle

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T1 - Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases)

AU - Storek, Jan

AU - Zhao, Zhao

AU - Lin, Eugene

AU - Berger, Thomas

AU - McSweeney, Peter A.

AU - Nash, Richard A.

AU - Akatsuka, Yoshiki

AU - Metcalf, Monja D.

AU - Lu, Hailing

AU - Kalina, Tomas

AU - Reindl, Markus

AU - Storb, Rainer

AU - Hansen, John A.

AU - Sullivan, Keith M.

AU - Kraft, George H.

AU - Furst, Daniel E.

AU - Maloney, David G.

PY - 2004/12/1

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N2 - To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years posttransplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months posttransplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pretransplant plasma cells.

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