[CIS PIDD] [cis-pidd] Puzzling X-linked SCID case

[CIS-PIDD]

Hi Angie,

I agree with your first thought about somatic reversion.  If your test was only looking for a switch back to wt sequence at the original mutation site, you could be missing a dowstream second mutation that might allow re-initiation.  I would suggest sequencing the full gene.  I'm wondering if you may need to do sorted sequencing to see enough of a signal.    Another possibility would be to look at transcripts of cd132, as I'm betting you will see a slightly shortened transcript in revertant cells.

Best
Mike

On Jan 21, 2017, at 12:05 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Hi all

I have an interesting post transplant X-linked SCID case and I’d like to see if others have thoughts about what is going on or have had similar cases.

The patient is a now 2 year old male with X-linked SCID (c.269+1G>A mutation). He was diagnosed based on NBS and family history. He had a matched sibling (2 year old healthy sister, not a carrier) who served as his bone marrow donor for his unconditioned transplant on 1/8/15. He had no transplant related complications and no infections. By day +28 after transplant he had >500 CD3 T cells, all of which were donor in origin. By 6 months post transplant, he was off immune globulin replacement, had normal lymphocyte numbers, proliferation, TRECs and RTE. T cells remained 100% donor.

At 1.5 years post transplant T cell donor chimerism had dropped to 20%. However, he continued to have normal lymphocyte numbers and B/T cell function. Now at 2 years out, his T cell chimerism is 9% donor. Lymphocyte numbers, immune globulin levels, proliferation, TREC, RTE all remain normal. Clinically doing fantastic — growing, developing normally, no infections.

Somatic reversion was considered and our molecular diagnostics lab designed a real time quantitative PCR specific for his mutation to investigate this. They did not find any evidence of somatic reversion.

He has never had myeloid donor chimerism. B cell donor chimerism has ranged from 5-10% and is stable. NK cell donor chimerism has ranged from 75-85% and is stable.

I’m stumped. Thanks in advance for any thoughts on why we are seeing a significant drop in T cell chimerism, but normal immune reconstitution.

Angie

----
Angela Smith, MD, MS
Assistant Professor
Pediatric Blood and Marrow Transplant
University of Minnesota
420 Delaware Street SE
MMC 484
Minneapolis, MN 55455
Phone 612 625 7253
Fax 612 626 2815


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