Study of thymic size and function in children and adolescents with treatment refractory systemic sclerosis eligible for immunoablative therapy.
Following hematopoietic stem cell transplantation (HSCT), thymic reconstitution of peripheral T lymphocytes is essential to avoid a chronically immunodeficient state and disease recurrence. The purpose of this study was to determine if children and adolescents with treatment refractory SSc, awaiting HSCT, have sufficient thymic function to reconstitute T lymphocyte function after transplantation. Thirteen children with systemic scleroderma were enrolled and assessed by physical exam, chest MRI, measurement of autoantibodies, B and T cell immuno-phenotyping, and quantization of T cell receptor rearrangement excision circles (TREC) as a marker of thymopoiesis. MRI detected thymic tissue in 9/13 children. TREC levels were detectable in all but one child but were significantly reduced (p<0.001) when compared to a control population. SSc patients also had a reduced percentage of naïve (CD45RA+CD31+) CD4+ T lymphocytes, further indicating diminished thymopoiesis. Our data suggest that thymic function in children with SSc might be insufficient for an adequate immunoreconstitution following transplantation in some patients. A thorough evaluation of immune and thymic functions to identify those patients prior to HSCT is recommended.
Reiff
A
A
Divisions of Rheumatology, Radiology and Bone Marrow Transplantation, Department of Pediatrics, University of Southern California, Keck School of Medicine, Children's Hospital Los Angeles, CA 90027, USA. reiff@hsc.usc.edu
Krogstad
P
P
Moore
S
S
Shaham
B
B
Parkman
R
R
Kitchen
C
C
Weinberg
K
K
D000293:Adolescent; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood / Q000276:immunology; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000276:immunology*; D055815:Young Adult
D000974:Antibodies, Antinuclear; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens