Use of Rituximab in Late Onset Leaky SCID
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Diana X. Nichols-Vinueza, MD, Hung S Luu, MD, Norberto Rodriguez Baez, MD, Yadira Rivera-Sanchez, MD, Kenneth S Chen, MD, Lee-Jun Wong, Ph.D, Hui Yu, Ph.D, M. Teresa De La Morena, MD
Rationale: At 9 years, a female with hypogammaglobulinemia, was diagnosed with EBV-encoded RNA (EBER) positive interstitial granulomatous lymphocytic lung disease in the setting of generalized lymphadenopathy and hepatosplenomegaly. Clinical improvement was noted after rituximab.

Methods: Severe-Combined-Immunodeficiency (SCID) comprehensive panel by Massively Parallel Sequencing was performed by Baylor Miraca Genetic Laboratories, Houston, TX.

Results: The patient had been diagnosed with common variable immunodeficiency after recurrent sinopulmonary infections and one episode of septic arthritis at 4 years and treated intermittently with intravenous immunoglobulin. At 9 years of age, she was noted to have failure to thrive, transaminitis, cholangitis, lymphadenopathy, hepatosplenomegaly, bronchiectasis and pulmonary nodules. IgG <140mg/dl, IgA<25mg/dl, IgM 130mg/dl; CD3 74 %/2831cells/mL, CD4 43%/1658cells/mL, CD8 22%/837cells/mL; NK 8%/309 cells/mL and CD19 17%/667 cells/mL; Normal response to phytohemagglutinin, pokeweed mitogen and tetanus. No mutation in activation-induced cytidine deaminase was detected.  Lung biopsy demonstrated granulomatous lymphocytic interstitial lung disease with scattered EBER+ cells; lymph node biopsy showed an atypical lymphoid hyperplasia but rare EBER+ cells and liver biopsy showed portal and lobular hepatitis with granulomas and few EBER+ cells. Blood EBV PCR detected at 29038 copies /ml. She received Rituximab and azathioprine. Pulmonary nodules and HSM markedly improved. 1 year later B cells had not recovered. At age 11 years genetic testing revealed a novel homozygous variant in RAG1 (c.1514T>G; p.L154R).

Conclusions: As previously described, children with hypogammaglobulinemia and granulomatous lesions merits genetic testing for leaky SCID, independent of age. Rituximab therapy may provide clinical benefit in patients with leaky SCID in the setting of lymphoproliferation and EBV.