Abstract
The human immune system depends on the activity of cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of familial hemophagocytic lymphohistiocytosis (FHL). Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL. The diagnosis, once based on a clinical constellation of abnormalities, is now strongly supported by the results of a functional flow-cytometry screening, which directs the genetic study. A few additional congenital immune deficiencies can also cause a resembling or even identical clinical picture to FHL. As in many other rare human disorders, the collection and analysis of a relatively large number of cases in registries is crucial to draw a complete picture of the disease. The conduction of prospective therapeutic trials allows investigators to increase the awareness of the disease and to speed up the diagnostic process, but also provides important functional and genetic confirmations. Children with confirmed diagnosis may undergo hematopoietic stem cell transplantation, which is the only cure known to date. Moreover, detailed characterization of these rare patients helped to understand the function of individual proteins within the exocytic machinery of CTL, NK, and NKT cells. Moreover, identification of these genotypes also provides valuable information on variant phenotypes, other than FHL, associated with biallelic and monoallelic mutations in the FHL-related genes. In this review, we describe how detailed characterization of patients with genetic hemophagocytic lymphohistiocytosis has resulted in improvement in knowledge regarding contribution of individual proteins to the functional machinery of cytotoxic T- and NK-cells. The review also details how identification of these genotypes has provided valuable information on variant phenotypes.
| Original language | English |
|---|---|
| Article number | Article 167 |
| Journal | Frontiers in Immunology |
| Volume | 5 |
| Issue number | APR |
| DOIs | |
| Publication status | Published - 2014 |
Fingerprint
Keywords
- Cellular cytotoxicity
- Hemophagocytosis
- Mutation analysis
- Natural killer
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Familial hemophagocytic lymphohistiocytosis : When rare diseases shed light on immune system functioning. / Sieni, Elena; Cetica, Valentina; Hackmann, Yvonne; Coniglio, Maria Luisa; Da Ros, Martina; Ciambotti, Benedetta; Pende, Daniela; Griffiths, Gillian; Aricò, Maurizio.
In: Frontiers in Immunology, Vol. 5, No. APR, Article 167, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Familial hemophagocytic lymphohistiocytosis
T2 - When rare diseases shed light on immune system functioning
AU - Sieni, Elena
AU - Cetica, Valentina
AU - Hackmann, Yvonne
AU - Coniglio, Maria Luisa
AU - Da Ros, Martina
AU - Ciambotti, Benedetta
AU - Pende, Daniela
AU - Griffiths, Gillian
AU - Aricò, Maurizio
PY - 2014
Y1 - 2014
N2 - The human immune system depends on the activity of cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of familial hemophagocytic lymphohistiocytosis (FHL). Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL. The diagnosis, once based on a clinical constellation of abnormalities, is now strongly supported by the results of a functional flow-cytometry screening, which directs the genetic study. A few additional congenital immune deficiencies can also cause a resembling or even identical clinical picture to FHL. As in many other rare human disorders, the collection and analysis of a relatively large number of cases in registries is crucial to draw a complete picture of the disease. The conduction of prospective therapeutic trials allows investigators to increase the awareness of the disease and to speed up the diagnostic process, but also provides important functional and genetic confirmations. Children with confirmed diagnosis may undergo hematopoietic stem cell transplantation, which is the only cure known to date. Moreover, detailed characterization of these rare patients helped to understand the function of individual proteins within the exocytic machinery of CTL, NK, and NKT cells. Moreover, identification of these genotypes also provides valuable information on variant phenotypes, other than FHL, associated with biallelic and monoallelic mutations in the FHL-related genes. In this review, we describe how detailed characterization of patients with genetic hemophagocytic lymphohistiocytosis has resulted in improvement in knowledge regarding contribution of individual proteins to the functional machinery of cytotoxic T- and NK-cells. The review also details how identification of these genotypes has provided valuable information on variant phenotypes.
AB - The human immune system depends on the activity of cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of familial hemophagocytic lymphohistiocytosis (FHL). Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL. The diagnosis, once based on a clinical constellation of abnormalities, is now strongly supported by the results of a functional flow-cytometry screening, which directs the genetic study. A few additional congenital immune deficiencies can also cause a resembling or even identical clinical picture to FHL. As in many other rare human disorders, the collection and analysis of a relatively large number of cases in registries is crucial to draw a complete picture of the disease. The conduction of prospective therapeutic trials allows investigators to increase the awareness of the disease and to speed up the diagnostic process, but also provides important functional and genetic confirmations. Children with confirmed diagnosis may undergo hematopoietic stem cell transplantation, which is the only cure known to date. Moreover, detailed characterization of these rare patients helped to understand the function of individual proteins within the exocytic machinery of CTL, NK, and NKT cells. Moreover, identification of these genotypes also provides valuable information on variant phenotypes, other than FHL, associated with biallelic and monoallelic mutations in the FHL-related genes. In this review, we describe how detailed characterization of patients with genetic hemophagocytic lymphohistiocytosis has resulted in improvement in knowledge regarding contribution of individual proteins to the functional machinery of cytotoxic T- and NK-cells. The review also details how identification of these genotypes has provided valuable information on variant phenotypes.
KW - Cellular cytotoxicity
KW - Hemophagocytosis
KW - Mutation analysis
KW - Natural killer
UR - http://www.scopus.com/inward/record.url?scp=84900860054&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84900860054&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2014.00167
DO - 10.3389/fimmu.2014.00167
M3 - Article
AN - SCOPUS:84900860054
VL - 5
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - APR
M1 - Article 167
ER -