[CIS PIDD] [cis-pidd] TACI and autoimmunity

[CIS-PIDD]

Dear Peter,

Eric Meffre and I published a paper last year in JACI (PMID: 26100089) on the immunologic consequences of TACI hemizygosity. We studied CVID patients with TACI null mutations (similar to your patient’s mutation) and patients who lost one TACI allele to a chromosomal deletion. Unlike CVID patients with classic TACI missense mutations who have lots of autoimmune diseases, our subjects had none. We’ve now studied nearly 80 of these patients and found a very low incidence of autoimmune disease.

Accordingly, I don’t think you can attribute your patient’s autoimmune features to her TACI mutation.

I hope this helps,

Neil


Neil Romberg, MD
Jeffrey Modell Chair of Pediatric Immunology Research
Attending Physician, Children’s Hospital of Philadelphia
Assistant Professor of Pediatrics, University of Pennsylvania
Abramson Suite 1216C
3615 Civic Center Blvd.
Philadelphia, PA 19104
(p) 267-426-8195
(f) 267-426-0363
www.romberglab.org



From: CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net>
Date: Wednesday, December 21, 2016 at 4:36 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net>
Subject: [cis-pidd] TACI and autoimmunity

Dear all,

We would appreciate your advice regarding a 28 year old woman with several autoimmune features: dactylitis, celiac disease, autoimmune thyroiditis and multiple sclerosis. No remarkable infections so far. She is currently under the care of our adult rheumatologist and more or less controlled with intermittent corticosteroids and teriflunomide.

Her most recent immunological data:
Normal number of T and B cells
Lowish NK cell numbers
Normal IgG (including subclasses), IgA and IgM levels, normal vaccine response (only total IgG2 levels for Pneumococcus available)

- 15,64% Tregs: CD4+/CD25+ of T CD4+, 0,79% with FoxP3 expression
- 9,85% TH17 CD4+/CD161+/CD196 of T CD4+ (and 2,04% of total lymphocytes)

- B cell panel:
   - 44,43%  (CD19+/IgD+/CD27-),
   - 47,00% (CD19+/CD27+)
   - 12,81%  (CD19+/IgD+/CD27+),
   - 34,19% (CD19+/IgD-/CD27+)
   - 8,56% (CD19+/IgD-/CD27-)
Transitional B cells: 6,47% d
CD21 low: 5,54%
Plasmablasts: 2,18% (2660 células/ml)

 CD4+/CD45RA+/CD45RO-: 39,91%
 CD4+/CD45RA-/CD45RO+: 40,39%
 CD4+/CD45RA+/CD45RO+: 18,31%
 CD8+/CD45RA+/CD45RO-: 61,41%
 CD8+/CD45RA-/CD45RO+: 19,77%
 CD8+/CD45RA+/CD45RO+: 15,81%
 CD4+/CD38+: 38,99%
 CD4+/HLA-DR+: 6,09%
 CD4+/CD38+/HLA-DR+: 1,64%
 CD4+/CD38-/HLA-DR-: 34,51%
 CD8+/CD38+: 61,14%
 CD8+/HLA-DR+: 14,00%
 CD8+/CD38+/HLA-DR+: 7,23%
 CD8+/CD38-/HLA-DR-: 32,09%

We included her in our in-house PID chip (IonTorrent platform) and found a heterozygous mutation in TACI with a stop codon just in the beginning of the gene (p.Arg9Ter), later confirmed by Sanger. No mutations were identified in other "candidate genes" such as CTLA4, LRBA, PIK3, STAT1, STAT3,..

Her father also carries the same mutation but he is completely asymptomatic. All other tested family members are asymptomatic and tested negative for the mutation.

We would appreciate your opinion regarding this "finding" and wonder if someone has been involved in the care of TACI patients with similar clinical/lab features (progressive autoimmune manifestations, low Tregs but apparently normal antibody production).

Many thanks in advance for your thoughts!

Peter Olbrich
FEA Pediatría
Infectologia Pediátrica e Inmunopatologias
H.U. Virgen del Rocío Sevilla
SPAIN


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