Presentation: Are Scleroderma Patients Less Microchimeric after Autologous Stem Cell Transplantation? (2007)

29 Are Scleroderma Patients Less Microchimeric after Autologous Stem Cell Transplantation?



PURPOSE- Fetal and maternal cells, so-called microchimerism (Mc), arising from bi-directional traffic of cells during pregnancy, has been found decades after delivery in healthy individuals and patients with Systemic Sclerosis or scleroderma (SSc) (1, 2). Patients had more frequent and/or quantitatively greater amounts of fetal and/or maternal Mc than healthy matched controls. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) trials have been tested in patients with severe diffuse SSc (3, 4). Subsequent immune reconstitution leads to change in full blood picture, and supposedly trigger to disease improvement.
The aim of our study was to examine whether fetal and/or maternal DNA prevalence was different in PBMC obtained from patients with diffuse SSc under AHSCT or not.
METHODS- Forty-five women and four men with diffuse disease were recruited in 5 french hospitals. Thirteen patients (12 females and 1 male) were under AHSCT protocol (0,5 -5 years post-transplant). All female patients were tested for male DNA, presumably fetal in origin by real-time PCR specific for a Y chromosome sequence (5). Detailed information on pregnancy and transfusion history was obtained. Six patients (4 males and 2 females) were tested for maternal Mc by HLA specific Quantitative PCR for the non inherited maternal HLA allele (2). Two patients (1 male and 1 female) were under AHSCT protocol.
RESULTS- Male DNA, presumably fetal in origin, was detected in PBMC from 13 out of 33 (39%) women with diffuse SSc who did not receive AHSCT treatment. On the contrary, none of the 10 women with diffuse SSc treated by ASCT protocol was found positive for Mc.
Maternal Mc was detected in PBMC from 1 out of 4 patients who did not receive AHSCT and not detected in the 2 patients after AHSCT protocol.
CONCLUSION- Fetal and maternal Mc have been commonly reported in patients with SSc. The absence of male DNA and or maternal DNA in PBMC after treatment by high dose chemotherapy plus ASCT in diffuse SSc patients is an intriguing observation. Although result is very preliminary, it merits further investigation to understand Mc depletion and its possible role in SSc remission observed after ASCT.
REFERENCES-
1. Nelson, J. L et al. 1998, Lancet 351:559.
2. Lambert, N. C et al. 2004, Arthritis Rheum 50:906.
3. Farge, D. et al. 2005, Arthritis Rheum 52:1555.
4. van Laar, J. M. et al. 2005, Ann Rheum Dis 64:1515.
5. Lambert, N. C et al. 2002, Blood 100:2845.

 J.M. Rak, None; D. Farge, None; F. Verrecchia, None; C. Deligny, None; J. Larguero, None; N.C. Lambert, None.