| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Abolhassani, H, et al.
(författare)
-
Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency
- 2017
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:1, s. 91-106
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three patients presented with EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8+ T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro–generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8+ T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70–CD27 interactions therefore play a nonredundant role in T and B cell–mediated immunity, especially for protection against EBV and humoral immunity.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Rezaei, N, et al.
(författare)
-
Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia
- 2008
-
Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 147:3, s. 255-259
-
Tidskriftsartikel (refereegranskat)abstract
- Severe congenital neutropenia (SCN) and CD40 ligand deficiency (CD40LD) are two primary immunodeficiency diseases caused by different underlying genetic defects. In this report, we present a case who clinically presented as a SCN patient, but subsequent mutation analysis of this patient was compatible with CD40LD. The patient is a 3-year-old boy, who was referred to our center because of pneumonia, oral and anal ulcers, and periodontitis. As severe consistent neutropenia and maturation arrest in the myeloid series were observed in the bone marrow, a diagnosis of SCN was made. However, no mutations were found in the <i>ELA2</i> and <i>HAX1</i> genes. As functional T cell defects were observed, we suspected CD40LD. DNA sequencing showed a 17-base pair deletion in the <i>CD40L</i> gene. Although the patient did not have a decreased serum level of IgA, and his serum IgM level was within the normal range, the diagnosis of CD40LD was confirmed, suggesting that CD40LD should be suspected in any male patient with recurrent infections and neutropenia.
|
|
