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Kawasaki disease and the T-cell antigen receptor
J Jason1, E Montana, J F Donald
1Department of Health and Human Services, Public Health Service, Atlanta, GA, USA.
We investigated the evidence for an infectious etiology of Kawasaki disease (KD), an acute vasculitis of unknown etiology, by assessing the effects of KD on the T cell antigen receptor variable beta region families (V beta). Using 3-color flow cytometry, we studied KD patients pre- and post-intravenous gamma globulin (IVIG) therapy and at > 40 days post therapy, additionally comparing them to matched pediatric control patients (PCC) and their own healthy parents (one parent/KD child). Of all the V beta families examined, only V beta 2 exhibited statistically significant differences, between the pre- and post-IVIG samples and preIVIG and parent samples. No associations were found between V beta 2 findings and T cell memory, activation, or adhesion markers. For 2 KD patients, 4 parents, and 1 PCC participant, > 15% of resting CD8+ lymphocytes and > 15% of blastic CD8+ lymphocytes expressed a single V beta family, which varied by individual, without similar expansions in the CD4+ cell populations. One of the participants with this abnormality was the only one with significant cardiac abnormalities. For all participants with the V beta abnormality, other T-cell abnormalities were extensive and involved both CD4+ and CD8+ cells. We suggest that V beta 2 changes do occur in KD, as previously reported. However, these may not be involved in disease pathogenesis. Other V beta changes also occur. Those occurring in parents may reflect asymptomatic reinfection with an infectious agent causing KD. Further, some KD patients may have restricted cytotoxic T-cell responses to that as yet unidentified agent; this restricted response may be associated with more severe cardiac involvement.
We investigated the evidence for an infectious etiology of Kawasaki disease (KD), an acute vasculitis of unknown etiology, by assessing the effects of KD on the T cell antigen receptor variable beta region families (V beta). Using 3-color flow cytometry, we studied KD patients pre- and post-intravenous gamma globulin (IVIG) therapy and at > 40 days post therapy, additionally comparing them to matched pediatric control patients (PCC) and their own healthy parents (one parent/KD child). Of all the V beta families examined, only V beta 2 exhibited statistically significant differences, between the pre- and post-IVIG samples and preIVIG and parent samples. No associations were found between V beta 2 findings and T cell memory, activation, or adhesion markers. For 2 KD patients, 4 parents, and 1 PCC participant, > 15% of resting CD8+ lymphocytes and > 15% of blastic CD8+ lymphocytes expressed a single V beta family, which varied by individual, without similar expansions in the CD4+ cell populations. One of the participants with this abnormality was the only one with significant cardiac abnormalities. For all participants with the V beta abnormality, other T-cell abnormalities were extensive and involved both CD4+ and CD8+ cells. We suggest that V beta 2 changes do occur in KD, as previously reported. However, these may not be involved in disease pathogenesis. Other V beta changes also occur. Those occurring in parents may reflect asymptomatic reinfection with an infectious agent causing KD. Further, some KD patients may have restricted cytotoxic T-cell responses to that as yet unidentified agent; this restricted response may be associated with more severe cardiac involvement.