Alexandra Y. Kreins, United Kingdom
Great Ormond Street Hospital Immunology and BMTPresenter of 1 Presentation
CLEARANCE OF CYTOMEGALOVIRUS INFECTION AFTER THYMUS TRANSPLANTATION IN A FOXN1-DEFICIENT PATIENT
Abstract
Background and Aims
Thymus transplantation (TT) can correct athymia with severe T-cell immunodeficiency secondary to FOXN1 deficiency. In presence of CMV infection, TT has previously never achieved thymopoeisis.
Methods
We describe the first patient with thymopoeisis and CMV clearance after TT.
Results
The patient displayed alopecia totalis at birth and at two months developed a desquamating erythematous rash followed by pneumonitis with CMV viraemia (viral load: 12xE6 copies/ml), which responded to anti-viral treatment. Additionally she suffered from BCGitis, improving after quadruple anti-mycobacterial treatment. Immunological assessment revealed lymphopaenia with oligoclonal T-cells, impaired mitogen proliferation, few naïve T-cells and low TREC levels. A homozygous FOXN1 mutation was identified, resulting in a premature stop codon (R114X). Upon referral to London, CMV viral load (VL) was low in serum (25xE3 copies/ml, CT33), but high in the CSF (CT26) with minimally raised protein, but no leukocytes. Except for a bulging fontanelle, she was neurologically asymptomatic. She underwent TT without anti-thymocyte globulin, but with cyclosporine to control Omenn-like features. With continuing anti-viral treatment, whole blood VL remained relatively low (maximum 34x10E3 copies/ml). At four months post-transplantation, she deteriorated neurologically, displaying features of mild encephalopathy and absence-like seizures after reduction in anti-viral treatment. After re-introduction of full treatment, her neurological status improved. At six months VL became undetectable in whole blood and CSF. Thymopoiesis was confirmed on transplant biopsy with simultaneous appearance of circulating naïve CD4 T-cells and recent thymic emigrants.
Conclusions
TT can be successful despite CMV disease, possibly because of low viraemia in our patient. Antiviral treatment did not impair thymopoeisis.