|
| Characteristics of the gene | Genes/loci | Immunological effects |
|
| Genes related to innate immune response | IRF5
TNFAIP3
IRAK1
STAT4
TREX1 | (i) IRF5 is the most consistent non-MHC gene in SLE and is important for transactivation of type 1 IFN and production of proinflammatory cytokines (IL6, IL12, TNF α, IL10). |
| (ii) Other genes also involved in pathways of type 1 IFN production. |
|
| Genes related to adaptive immune response (T-cell signaling) | HLA-DR
PTPN22
STAT4
PDCD1
IRAK1
TNFSF4 | (i) HLA region at 6p21.3 has shown strongest association with SLE. MHC class II genes influence antigen presentation by interacting with T cell receptor (TCR), and susceptible HLA haplotype contributes to abnormal response to self antigens. |
| (ii) Other genes are involved in hyperactivity of T cells and failure of multiple immunoregulatory circuits to down-regulate those responses. |
|
| Genes related to adaptive immune response (B-cell signaling) | HLA-DR
BLK
BANK1
LYN | These genes are involved in hyperactivity of B cells and failure of multiple immunoregulatory circuits to downregulate those responses. |
|
| Genes related to immune complex clearing | Complements
(C1q, C2, C4)
FCGR2A
FCGR3A
CRP
ITGAM | (i) These genes are associated with dysregulated and inadequate immune complex clearance in SLE. |
| (ii) ITGAM encodes integrin α M (complement receptor type 3) and is involved in immune complex clearance, leukocyte activation, phagocytosis, and adhesion to endothelia through interaction with multiple ligands, for examples, ICAM-1, C3bi, fibrinogen, glycoprotein Iba. ITGAM gene plays a key role in SLE pathogenesis, especially through endothelial injury. |
| (iii) FCGR2A and FCGR3A genes code the IgG Fc receptor IIA and IIIA. The lupus predisposing polymorphisms in these genes relate to poor binding to IgG and phagocytosis of immune complexes. |
|
| Other genes in SLE pathogenesis | MECP2
ATG5 | (i) MECP2 is involved in DNA methylation. |
| (ii) ATG5 is involved in apoptosis. |
|
