[CIS PIDD] [cis-pidd] Heterozygous RAG1 mutation, isolated CD4 lymphopenia, warts and bone marrow hypoplasia

[CIS-PIDD]

Dear all,

We are evaluating a 23yo male with idiopathic CD4 lymphopenia (~150-200 T
CD4) clinically he presented with:
- generalized verrucosis (since age 16)
- slowly progressive signs of bone marrow hypoplasia: macrocytic anemia (Hb
~11, MCV 100), thrombocytopenia (Plt ~100.000), normal neutrophils.
Hypoplastic bone marrow, with lymphoid infiltrates. No molecular
abnormalities in the BM.
- autoimmune thyroiditis
- vitiligo (as Koebner phenomenon around the warts)
- otherwise healthy, without history of infections in spite of the
lymphopenia

Normal Ig, with slightly elevated IgE
IgM 0.6 g/L
IgA 1.05 g/L
IgG 10.2 g/L
IgE 394

Lymphopenia, mainly CD4 with reduced naive compartment, inverted CD4/8
ratio and elevated T g/d lymphocytes.
Lymphocytes 820
T CD4 170
T CD8 326
T GD 159
B 60
NK 28
T CD4 Naive (CD45RA+/CCR7+) 4.9%
T CD4 TEM (CD45RA-/CCR7-) 67.5 %
T CD4 TCM (CD45RA-/CCR7+) 24 %
T CD4 TEMRA (CD45RA+/CCR7-) 3.50%

Reduced TREC, normal KREC

High titer ANA antibodies (>1:640, SP pattern), + anti-Pm/Scl antibodies
Anti-TPO antibodies and anti-TG antibodies

WES found an unreported heterozygous RAG1 mutation, in an highly conserved
area of the Zn binding domain, predicted to be damaging.

My questions:

1) How to manage the warts? They are resistant to topical therapies and
relapse after surgical excision. Furthermore an high risk HPV strain was
isolated, rising serious concerns about cancerous evolution. Interferon was
proposed as an option, but we are worried about autoimmune manifestations.
Does anyone have any experiences?

2) Have you ever seen this bone marrow picture with RAG mutations?

3) Is there someone (possibly in Italy or Europe) who can evaluate the
recombinase activity, to confirm the mutation relevance?

Sorry for the lenghty email, and thanks in advance,
Kind regards,

Dr. Boaz Palterer
Dept. of Clinical and Experimental Medicine
Allergology and Clinical Immunology
University of Florence, Italy
cell. +39 3927169114 <+39%20392%20716%209114>
email. boaz.palterer at gmail.com

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