Table 1.
Human diseases involving defects in CD46-mediated signals or required co-signals
| Disease | Pathology | Aetiology | CD46-related functional defect | References |
|---|---|---|---|---|
| aHUS (atypical haemolytic uraemic syndrome) | Triad of haemolytic anaemia, thrombocytopenia, and acute renal failure | CD46 gene mutations | Defective complement regulation specifically on endothelium | Richards, 2003; Maga, 2010 |
| Multiple sclerosis | Chronic autoimmune disorder leading to cognitive disabilities due to demyelination of axons in the brain and spinal cord | Unknown | Defective regulation of autoreactive effector T cells: | Astier, 2006; Martinez-Forero et al., 2008; Yao, 2010; Vaknin-Dembinsky, 2008 |
| • reduced IL-10 production (lack of Th1 regulation) | ||||
| • excessive Th17 expansion | ||||
| • increased IL-23p19 production by DCs (further amplifying Th17 activation) | ||||
| Rheumatoid arthritis | Chronic and systemic disorder principally leading to the destruction of articular cartilage and ankylosis of the joints | Unknown | Defective regulation of autoreactive effector T cells: | Cardone, Le Friec, 2010 |
| • defective IFN-γ‘shut-down’ | ||||
| • (lack of Th1 regulation) | ||||
| Asthma | Chronic inflammatory disease of the airways characterized by airway obstruction and bronchospasm | Unknown | Defective effector T cell regulation: | Xu et al., 2010 |
| reduced IL-10 production | ||||
| IPEX-like syndrome | Severe immune dysregulation, polyendocrinopathy and enteropathy | †CD25 deficiency – absence of IL-2-mediated signals required for CD46-induced cytokine production | Defective effector T cell induction and regulation: | Caudy, 2007 |
| • ‡absence of regulatory Th1/Tr1 cells | ||||
| Primary C3 deficiency | Recurrent and severe infections due to compromised functions of vital immune cells (including DCs, B cells and T cells) | C3 gene mutation (lack of CD46 ligand expression?) | Defective effector T cell induction and regulation: | Ghannam, 2008 |
| • no IL-10 production and reduced IFN-γ production upon CD46 activation | ||||
| • defective B cell memory compartment |
†
The cause of CD25 deficiency in this patient is unknown.
‡
The production of IFN-γ after CD3/CD46/IL-2 activation of CD4+ T cells from this patient was not analysed in this study. IL: interleukin; IPEX: immunodysregulation polyendocrinopathy enteropathy X-linked syndrome; Th: T helper; DCs: dendritic cells; IFN: interferon.