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Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as "composite" (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P = .013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P = .047) and the composite outcome (P = .017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.

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OBJECTIVE To review the outcome of patients with pathogenic variants in FLNA and progressive lung disease requiring lung transplantation. STUDY DESIGN We conducted a retrospective chart review of six female infants with heterozygous presumed loss of function pathogenic variants in FLNA whose initial presentation was early and progressive respiratory failure. RESULTS Each patient received lung transplantation at an average age of 11 months (range: 5 to 15 months). All patients had pulmonary arterial hypertension and chronic respiratory failure requiring tracheostomy and escalating levels of ventilator support prior to transplantation. All six patients survived initial lung transplantation; however, one patient died after a subsequent heart-lung transplant. The remaining five patients are living unrestricted lives on chronic immunosuppression at most recent follow-up (range: 19 months to 11.3 years post-transplantation). However, in all patients, severe ascending aortic dilation has been observed with aortic regurgitation. CONCLUSIONS Respiratory failure secondary to progressive obstructive lung disease during infancy may be the presenting phenotype of FLNA-associated periventricular nodular heterotopia. We describe the largest cohort of patients with progressive respiratory failure related to a pathogenic variant in FLNA and present lung transplantation as a viable therapeutic option for this group of patients.