PMID- 11986222
OWN - NLM
STAT- MEDLINE
DCOM- 20020610
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 10
DP  - 2002 May 15
TI  - Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different 
      immunosuppressive regimens.
PG  - 3668-75
AB  - We studied the degree and the pattern of skewing of the variable region of 
      beta-chain (VB) T-cell receptor (TCR) repertoire in aplastic anemia (AA) at 
      initial presentation and after immunosuppression using a high-resolution analysis 
      of the TCR VB complementarity-determining region 3 (CDR3). Age-matched healthy 
      individuals and multitransfused patients with non-immune-mediated hematologic 
      diseases were used as controls. In newly diagnosed AA, the average frequency of 
      CDR3 size distribution deviation indicative of oligoclonal T-cell proliferation 
      was increased (44% +/- 33% vs 9% +/- 9%; P =.0001); AA patients with human 
      leukocyte antigen (HLA)-DR2 and those with expanded paroxysmal nocturnal 
      hemoglobinuria clones showed more skewed VB repertoires. Nonrandom oligoclonal 
      patterns were found for VB6, VB14-16, VB21, VB23, and VB24 subfamilies in more 
      than 50%, and for VB15, VB21, and VB24 in more than 70% of AA patients with 
      HLA-DR2. Patients received immunosuppression with antithymocyte globulin 
      (ATG)/cyclosporine (CsA) or cyclophosphamide (CTX) with CsA in combination, and 
      their VB repertoire was reanalyzed after treatment. Whereas no significant change 
      in the degree of VB skewing in patients who had received ATG was seen, patients 
      treated with CTX showed a much higher extent of oligoclonality within all VB 
      families, consistent with a profound and long-lasting contraction of the T-cell 
      repertoire. VB analysis did not correlate with the lymphocyte count prior to 
      lymphocytotoxic therapy; however, after therapy the degree of VB skewing was 
      highly reflective of the decrease in lymphocyte numbers, suggesting iatrogenic 
      gaps in the VB repertoire rather than the emergence of clonal dominance. Our data 
      indicate that multiple specific clones mediate the immune process in AA.
FAU - Kook, Hoon
AU  - Kook H
AD  - Hematology Branch of the National Heart, Lung, and Blood Institute, National 
      Institutes of Health, Bethesda, MD, USA.
FAU - Risitano, Antonio M
AU  - Risitano AM
FAU - Zeng, Weihua
AU  - Zeng W
FAU - Wlodarski, Marcin
AU  - Wlodarski M
FAU - Lottemann, Craig
AU  - Lottemann C
FAU - Nakamura, Ryotaro
AU  - Nakamura R
FAU - Barrett, John
AU  - Barrett J
FAU - Young, Neal S
AU  - Young NS
FAU - Maciejewski, Jaroslaw P
AU  - Maciejewski JP
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anemia, Aplastic/diagnosis/drug therapy/*genetics
MH  - Antilymphocyte Serum/therapeutic use
MH  - Child
MH  - Complementarity Determining Regions/genetics
MH  - Cyclophosphamide/therapeutic use
MH  - Cyclosporine/therapeutic use
MH  - *Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Lymphocyte Count
MH  - Middle Aged
MH  - Receptors, Antigen, T-Cell, alpha-beta/*genetics
EDAT- 2002/05/03 10:00
MHDA- 2002/06/11 10:01
CRDT- 2002/05/03 10:00
PHST- 2002/05/03 10:00 [pubmed]
PHST- 2002/06/11 10:01 [medline]
PHST- 2002/05/03 10:00 [entrez]
AID - S0006-4971(20)60846-1 [pii]
AID - 10.1182/blood.v99.10.3668 [doi]
PST - ppublish
SO  - Blood. 2002 May 15;99(10):3668-75. doi: 10.1182/blood.v99.10.3668.