[CIS-PAGID] Transplantation for APECED ?

[Elie Haddad]

You should ask to Jean-Laurent Casanova.
Elie


Elie Haddad, MD, PhD;
Professor of Pediatrics, University of Montreal,
Head, Pediatric Immunology and Rheumatology Division,
CHU Sainte-Justine, 3175 Cote Sainte-Catherine
Montreal, QC, H3T 1C5, Canada
Ph: 1 514 345 4713
fax: 1 514 345 4897
e-mail: elie.haddad at umontreal.ca




Le 2011-07-13 à 23:29, Kimberly Risma a écrit :


> Colleagues,  Somewhat related to the subject of APECED, is anyone offering screening for anti-IL-17 antibodies or defects in IL-17 signaling, either for research purposes or clinical testing in patients with mucocutaneous candidiasis? Thanks, Kim

> 

>  

> Kimberly Risma MD, PhD

> Assistant Professor

> Allergy Immunology

> Childrens Hospital Medical Center

> 3333 Burnet Ave, mlc 2000

> Cincinnati, OH 45229

> Kimberly.Risma at cchmc.org >>> "Notarangelo, Luigi" <Luigi.Notarangelo at childrens.harvard.edu> 7/13/2011 2:08 PM >>>

> Dear Elie:

> 

> As you pointed out, HCT should not work for APECED because Aire is mostly expressed by mTECs. However, it is interesting to know that conflicting results have been obtained with HCT in aire KO mice, with two groups reporting either complete failure or successful correction of autoimmunity. I do not think that anybody has looked carefully into this, and I wonder whether: a) “resetting” of the immune system could be explanation for success 9at least in some cases); or b) aire expression by donor-derived myeloid cells might partially compensate for the defect. In any case, I think there is insufficient evidence (if any) that HCT would work, unless you bet specifically on resetting of the immune system (but even so, attempts with autologous HCT for autoimmunity are less popular now than they were until few years ago, I guess?)

> 

> Gigi

> 

> 

> Luigi D. Notarangelo, M.D.

> Jeffrey Modell Chair of Pediatric Immunology Research in Boston

> Director, Research and Molecular Diagnosis Program on Primary Immunodeficiencies

> Division of Immunology, Children's Hospital

> Professor of Pediatrics and Pathology, Harvard Medical School

> Karp Building, 9th floor, Rm 09210

> 1 Blackfan Circle

> Boston, MA 02115

> USA

> 

> (tel) (617)-919-2276

> (fax) (617)-730-0709

> 

> 

> Secretary: Luisa Raleza

> email: luisa.raleza at childrens.harvard.edu

> 

> 

> 

> 

> On 7/13/11 12:04 PM, "Elie Haddad" <elie.haddad at umontreal.ca> wrote:

> 

> Dear all,

> I follow a 22 years old girl with APECED (proven AIRE mutation) with very severe autoimmunity.

> The only treatment that was considered efficient was Rituximab for many years (since 2005) and she was treated by one injection every 6 months. I informed the patient about the risks of repeating Rituximab but she said that her endocrinologic autoimmunity was very uncomfortable and the only treatment that worked was Rituximab and she did not want to stop.

> 18 months ago, she presented with extensive pulmonary embolism related with deep venous thrombosis (we did not understand why she did this) that could be efficiently treated. During the hospitalization, we noticed a very severe anemia that did not resolve and that was eventually considered as autoimmune central anemia. Indeed, the anemia was central, Epo was normal, there was no anti-Epo antibodies, and marrow specimen showed plenty of T cells infiltrating the marrow and surrounding reticulocytes (I could not see the slides, this is what said the haematologist). To treat this autoimmune central anemia, we stopped Rituximab and tried ATG + FK506 and then MMF in accordance with haematologist advise. This treatment was unsuccessful and she is presently transfused with red cells every 3 weeks with ferritin dangerously growing up (even if somewhat stabilized by oral iron chelation)…

> We are therefore facing a very severe autoimmune central anemia that is resistant to Rituximab (that has been restarted recently to control her endocrinologic autoimmunity), MMF, anti-Calcineurine, ATG. She is under sub-cu IG for immunoglobulin replacement because of repeated rituximab. Given the T cell infiltrate in marrow (that is not a leukemic infiltrate), we consider that we are facing a T cell autoimmunity and we don’t feel that plasmapheresis could work.

> The question is regarding bone marrow transplantation. I know it may be a strange idea but our haematologist colleagues propose to perform an allogenic HSCT. I would like to have your opinion. Given that AIRE deficiency is a thymic disorder, allogenic HSCT should not work. The only way it could work would be that thymus function in older patients is not perfect and that the new immune system may not be miseducated. However, if this theory works, then an autologous HSCT after « radical » immunosuppression to “reset” the immune system should work also and would be less dangerous than an allo-HSCT.

> What do you think ? Allo ? Auto ? Has anyone already done an HSCT for APECED ? HSCT (auto or allo) doesn’t make any sense ? Other proposition to treat this autoimmunity?

> Thank you for your feedback.

> Elie

> 

> PS: sorry for the long text (it’s a complicated story), and sorry for the possible English mistakes from a “French” Canadian.

> 

> 

> Elie Haddad, MD, PhD;

> Professor of Pediatrics, University of Montreal,

> Head, Pediatric Immunology and Rheumatology Division,

> CHU Sainte-Justine, 3175 Cote Sainte-Catherine

> Montreal, QC, H3T 1C5, Canada

> Ph: 1 514 345 4713

> fax: 1 514 345 4897

> e-mail: elie.haddad at umontreal.ca

> 

> 

> 

> 


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