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.
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
A
A
Reiff
P
P
Krogstad
S
S
Moore
B
B
Shaham
R
R
Parkman
C
C
Kitchen
K
K
Weinberg
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