Introduction: Hypogammaglobulinemia (HG) is associated with poor outcomes in adult heart transplant recipients but is not well studied in pediatric recipients. We therefore investigated longitudinal immunoglobulin (Ig) levels in 15 pediatric heart transplant cases. Methods: Sera were collected from 15 recipients at a median of 3.2 mo (visit 1), 8.5 mo (visit 2), and 22.3 mo (visit 3) post transplant and from 9/15 candidates pre transplant. IgG subclasses 1-4, IgM, and IgA were quantified by bead-based multiplex immunoassay. Total IgG was calculated by summation of subclasses, using scoreable values or the assay's lower limit of detection. HG was defined as Ig level below the lower limit of the 95% CI for age. Results: Median age at transplant was 12.9 yrs (1.4-21yrs); 5/15 required ECMO or LVAD pre transplant. Induction consisted of ATG and solumedrol, followed by maintenance tacrolimus and MMF. No participant received anti-CD20 mAb or IVIG. All 9 transplant candidates had HG pre transplant (mean IgG 306 ±144 mg/dL), which was attributed primarily to low IgG1 (8, 1, 4, and 6 candidates had IgG1, IgG2, IgG3, and IgG4 <95%CI for age, respectively). HG persisted post transplant, with mean IgG levels of 332 ± 142 at visit 1, 324 ± 133 at visit 2, and 390 ± 162 at visit 3. Low IgG again reflected primarily low IgG1; 11, 3, 3, and 8 participants had IgG1, IgG2, IgG3 and IgG4 <95% CI for age, respectively. In addition, at least 50% of participants had low IgM and/or IgA at visits 1-3. Only 1 child with pre transplant HG had normal levels of all isotypes by visit 3. 2 candidates had bacteremia, and 1 had fungemia pre transplant. 6 children had opportunistic infection post transplant (4 CMV, 1 EBV, 1 adenovirus). Conclusions: Studies in adult solid organ transplant recipients suggest that HG is medication-induced. However we found that HG began prior to transplant and persisted until at least 2 years post transplant. HG reflected low levels of IgG1, which may result in recurrent infections and impaired vaccine responses. The mechanisms contributing to both pre transplant HG and persistent HG beyond the early post transplant period require further investigation. If confirmed in larger studies, these data may provide a rationale for randomized trials of IVIG replacement in pediatric SOT recipients.

CITATION INFORMATION: Madan R, Penkert R, Dara J, Lamour J, Herold B, Hurwitz J. Hypogammaglobulinemia in Pediatric Heart Transplant Candidates Is Not Corrected by Transplantation. Am J Transplant. 2017;17 (suppl 3).

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