Birgitta Versluijs

57 Association between respiratory virus and alloimmune lung syndromes influence on alloreactive T cells of immunosuppressive agents used to treat aGVHD grade II-IV. None of our patients had lung involvement at the onset of aGVHD. This may be because the lungs are less susceptible to acute alloreactivity than the classic tar- get organs of gut, liver, and skin. This is also reflected by the fact that the median time to allo-LS was longer (8 weeks) than the median time to aGVHD (4 weeks). All patients who developed allo-LS did so during tapering of immunosuppressive therapy or after this therapy had been stopped. All of the patients with aGVHD where on prolonged im- munosuppressive therapy (including steroids) and thus likely had less chance to develop alloimmunity in the lungs. In other words, the RV-positive patients who did not develop allo-LS had significantly greater immune suppression than the RV-positive patients who did develop allo-LS (data not shown). This effect of immunosuppressive therapy on the development of allo-LS is in line with previous findings. 31 Regarding cGVHD, in contrast to other studies, in our cohort, only 1 of 12 patients (11%) with BOS had signs of cGVHD in other organs. Our finding of no association between cGVHD and BOS/BOOP might be because of the generally low incidence of cGVHD in the pediatric HSCT population. This, together with the fact that viral infections are more frequent in childhood, might make the respiratory epithelium a preferential target for chronic allo-reactivity, at least in this pediatric cohort. No protective effect of cGVHD on the development of allo-LS was noted, most likely because cGVHD (mainly the limited form) was not treated with systemic immunosuppressive agents (eg, steroids). A similar association between RV infection and allo-LS has been reported after lung transplantation. A recent prospective cohort study in 100 lung transplant recipients clearly showed had significantly more acute or chronic rejection episodes in patients with an RV infection occurring within 100 days post-transplantation. 18 BOS occurring af- ter lung transplantation is considered a manifestation of allograft rejection 32,33 because of an alloimmune process. Some animal models of lung transplantation have demonstra- ted an association between the presence of RV and the development of BOS exclusively in the allogeneic transplantation setting. 34 These results are in line with the association between RV infection and allo-LS seen in our HSCT population, and strongly support the hypothesis that airway damage from an RV infection alone does not lead to severe pro- blems, but triggers alloimmunity. Because of this strong association, the current practice in lung transplantation is to increase immunosuppression by adding steroids in the pre- sence of an RV infection posttransplantation, to avoid rejection (personal communica- tion Lung transplantation programme UMC Groningen and UMC Utrecht, 2007). This practice has led to a decreased graft rejection rate. Increasing immunosuppression solely because of the presence of a RV may sound pa- radoxical, possibly predisposing the patient to other potentially life-threatening compli- cations, but it is supported by our observation that patients with RV infection early after HSCT were less vulnerable to allo-LS when receiving immunosuppression for aGVHD. 3