Autologous stem cell transplantation for paediatric-onset polyarteritis nodosa: changes in autoimmune phenotype in the context of reduced diversity of the T- and B-cell repertoires, and evidence for reversion from the CD45RO(+) to RA(+) phenotype.
We have studied immune reconstitution in a patient with paediatric-onset polyarteritis nodosa treated with high-dose immunosuppressive agents followed by stem cell rescue. The patient developed several new autoimmune phenomena over the 18 months after immunosuppression and stem cell rescue. Flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) heteroduplex and isotype-specific RT-PCR analysis of immunoglobulin expression showed that the T- and B-cell repertoires were highly restricted in the first few months after treatment. The dominant T-cell clones seen after reconstitution were persistently expanded, were different from those which could be demonstrated before autologous stem cell transplantation, and were in the CD8(+) population. Our data also show that 12 months after treatment these expanded T-cell clones were within the CD45RA(+) population, suggesting that reversion from the CD45RO(+) to the CD45RA(+) phenotype had occurred in vivo.
Wedderburn
L R
LR
Paediatric Rheumatology Unit, Institute of Child Health and Department of Molecular Pathology, University College London, London, UK.
Jeffery
R
R
White
H
H
Patel
A
A
Varsani
H
H
Linch
D
D
Murray
K
K
Woo
P
P
D000328:Adult; D017668:Age of Onset; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D015415:Biomarkers; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D020180:Heteroduplex Analysis; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007165:Immunosuppression Therapy; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D010488:Polyarteritis Nodosa / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014182:Transplantation, Autologous
D015415:Biomarkers; D017493:Leukocyte Common Antigens