Abstract
A defective switching off of the immune response is involved in several autoimmune diseases. This switching off involves Fas-mediated apoptosis, perforin-mediated fratricide of activated lymphocytes, and the suppressive activity of regulatory T (Treg) cells. These mechanisms are altered in autoimmune lymphoproliferative syndrome that often displays autoimmune thrombocytopenia. The aim of this research was to evaluate these mechanisms in adult patients with primary immune thrombocytopenia (ITP), compared with healthy controls. The results show that a substantial subgroup of the ITP patients displayed a defective Fas function; most of them displayed decreased Fas expression in T cells activated in vitro. Moreover, ITP patients displayed an increased frequency of rare missense variations of the PRF1 gene and decreased levels of Treg. Immunological analysis showed that levels of Interleukin (IL)10 and IL17 were decreased and marginal zone B cells were increased. Moreover, myeloid and plasmacytoid dendritic cells were decreased in ITP patients. In conclusion, in adult ITP patients, several mechanisms involved in shutting off the immune response are defective and several immunological parameters are dysregulated; these alterations may play a role in the clinical heterogeneity of the disease.
| Original language | English |
|---|---|
| Journal | British Journal of Haematology |
| DOIs | |
| Publication status | Accepted/In press - 2016 |
Fingerprint
Keywords
- Cytokine secretion
- Fas function
- Immune thrombocytopenia
- PRF1 variations
- Treg
ASJC Scopus subject areas
- Hematology
Cite this
Decreased function of Fas and variations of the perforin gene in adult patients with primary immune thrombocytopenia. / Boggio, Elena; Gigliotti, Casimiro L.; Rossi, Davide; Toffoletti, Eleonora; Cappellano, Giuseppe; Clemente, Nausicaa; Puglisi, Simona; Lunghi, Monia; Cerri, Michaela; Vianelli, Nicola; Cantoni, Silvia; Tieghi, Alessia; Beggiato, Eloise; Gaidano, Gianluca; Comi, Cristoforo; Chiocchetti, Annalisa; Fanin, Renato; Dianzani, Umberto; Zaja, Francesco.
In: British Journal of Haematology, 2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Decreased function of Fas and variations of the perforin gene in adult patients with primary immune thrombocytopenia
AU - Boggio, Elena
AU - Gigliotti, Casimiro L.
AU - Rossi, Davide
AU - Toffoletti, Eleonora
AU - Cappellano, Giuseppe
AU - Clemente, Nausicaa
AU - Puglisi, Simona
AU - Lunghi, Monia
AU - Cerri, Michaela
AU - Vianelli, Nicola
AU - Cantoni, Silvia
AU - Tieghi, Alessia
AU - Beggiato, Eloise
AU - Gaidano, Gianluca
AU - Comi, Cristoforo
AU - Chiocchetti, Annalisa
AU - Fanin, Renato
AU - Dianzani, Umberto
AU - Zaja, Francesco
PY - 2016
Y1 - 2016
N2 - A defective switching off of the immune response is involved in several autoimmune diseases. This switching off involves Fas-mediated apoptosis, perforin-mediated fratricide of activated lymphocytes, and the suppressive activity of regulatory T (Treg) cells. These mechanisms are altered in autoimmune lymphoproliferative syndrome that often displays autoimmune thrombocytopenia. The aim of this research was to evaluate these mechanisms in adult patients with primary immune thrombocytopenia (ITP), compared with healthy controls. The results show that a substantial subgroup of the ITP patients displayed a defective Fas function; most of them displayed decreased Fas expression in T cells activated in vitro. Moreover, ITP patients displayed an increased frequency of rare missense variations of the PRF1 gene and decreased levels of Treg. Immunological analysis showed that levels of Interleukin (IL)10 and IL17 were decreased and marginal zone B cells were increased. Moreover, myeloid and plasmacytoid dendritic cells were decreased in ITP patients. In conclusion, in adult ITP patients, several mechanisms involved in shutting off the immune response are defective and several immunological parameters are dysregulated; these alterations may play a role in the clinical heterogeneity of the disease.
AB - A defective switching off of the immune response is involved in several autoimmune diseases. This switching off involves Fas-mediated apoptosis, perforin-mediated fratricide of activated lymphocytes, and the suppressive activity of regulatory T (Treg) cells. These mechanisms are altered in autoimmune lymphoproliferative syndrome that often displays autoimmune thrombocytopenia. The aim of this research was to evaluate these mechanisms in adult patients with primary immune thrombocytopenia (ITP), compared with healthy controls. The results show that a substantial subgroup of the ITP patients displayed a defective Fas function; most of them displayed decreased Fas expression in T cells activated in vitro. Moreover, ITP patients displayed an increased frequency of rare missense variations of the PRF1 gene and decreased levels of Treg. Immunological analysis showed that levels of Interleukin (IL)10 and IL17 were decreased and marginal zone B cells were increased. Moreover, myeloid and plasmacytoid dendritic cells were decreased in ITP patients. In conclusion, in adult ITP patients, several mechanisms involved in shutting off the immune response are defective and several immunological parameters are dysregulated; these alterations may play a role in the clinical heterogeneity of the disease.
KW - Cytokine secretion
KW - Fas function
KW - Immune thrombocytopenia
KW - PRF1 variations
KW - Treg
UR - http://www.scopus.com/inward/record.url?scp=84994083608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994083608&partnerID=8YFLogxK
U2 - 10.1111/bjh.14248
DO - 10.1111/bjh.14248
M3 - Article
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
ER -