[CIS PIDD] [cis-pidd] Late onset profound CD4 lymphopenia and absent thymopoeisis

[CIS-PIDD]

Dear All,

I’d greatly appreciate advice on the diagnosis and further management of a 47 year-old male that I have been consulted on, but not yet seen. Over the past five years he has lost 5 kg in weight. He has had recurrent painful ulcers and  abdominal pain. He has seen many doctors and undergone extensive investigations.  Endoscopy was apparently negative 2 years ago. Leukopenia is documented periodically, with consistent lymphopenia. Since 2015 absolute CD4 count has ranged from 6-17, CD4% 1-5.8%. Repeated HIV ELIZA and PCR are all negative. In 2014 he was treated for TB larynx for 6 months but other than that haven’t been any documented infections. At the age of 15 he underwent surgery for congenital ureter stenosis.
Family history: his father died of lymphoma at age of 46.
Immune Results
He has normal serum levels IgG, IgA, IgM & IgE but on SPEP they documented paraprotein of 2-3 g/L – immune fixation Lamda.
Hepatitis B surface AG & AB – both negative. Hep C AB – negative.
CD4/8 on 17 October 2017:  TLC 558 cells/ul, total CD3 – 252,  CD4 % - 3%, abs CD4 – 15 cells/ul. Abs CD8 – 215, CD8 % - 39, CD4/8 ratio = 0.07 (here the absolute CD4 count was  determined by negative dating, by positive labelling of CD8 within CD3, in order to exclude OKT4 epitope deficiency).
On 2 October 2017: Abs lymphocyte was 0.74 (1-4 normal range), CD3+ abs 260 cells/ul, CD3% was low at 39.8, CD4% - 3, CD4 abs – 21. Total B-cells abs 56 cells/ul, Total NK abs – 260 cells/ul
Recent Thymic emigrants – 1 (50-2400)
Total naïve helper – 0 (11 -824)
Central memory helper – 9 (58 - 413)
Effector memory helper – 13.1 (7-99)
Total naïve cytotoxic  -  1 (4 - 475)
Central memory cytotoxic -  6.1 (6 -135)
Effector memory cytotoxic – 83.5 ( 0 -36)
Alpha  Beta TCR – 69 %
Gamma Delta TCR – 6 %
TREC – absent
KREC – present
TCR PCR – positive for the detection of clonal TCR gamma chain and beta gene rearrangements consistent with the presence of a clonal  cell population,  i.e. a haematological malignancy.
Lymphocyte proliferation:  Reduced LPT to PHA, PMA, PMA & ionomycin, anti-CD3, but normal proliferation to anti-CD3 plus IL-2.
                                                     Absent Ag response to Candida, Tetanus, Pokeweed mitogen.
                                                     Reduced LPT to varicella Zoster.

Bone marrow aspirate and trephine biopsy 2015: Cellular marrow, ~ 1% plasma cells, compatible with MGUS. Currently CRAB tests normal

CT chest, Abdomen & Pelvis 11 October 2017:  Nil overtly suspicious lesions, multiple subcentimeter pre-tracheal nodes.

I’m clearly worried about haematological malignancy/lymphoma but haematology oncologists with whom his case was discussed apparently said  that no lymphoma presents like this.
Idiopathic CD4+ lymphopenia is a heterogenous condition but TRECS and RTI are apparently normal there, unlike the reduced values shown here. Could this be a late onset PID/combined immune deficiency?
It’s remarkable how apparently well he is and works full time. I recommended Bactrim prophylaxis, I’m also concerned about MAC and cryptosporidium but he has no diarrhea.

I’d really value suggestions for further tests (? genetic panel) and treatment.

Many thanks.

Stanley Ress

Emeritus Associate Professor of Medicine, UCT
Specialist physician & Clinical Immunologist,
UCT Private Academic hospital, Anzio Road, Observatory,

Cape Town, 7925
South Africa
TEL:INTERN<tel:INTERN>. + 2721-4421966 or 4421816
FAX:   "    + 2721-(0)865173095

Cell: 0833115482
email: stan.ress at uct.ac.za<mailto:stan.ress at uct.ac.za>



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