Immunogenetic mechanism of lupus disease
1. Tolerance to self-antigens is called self-tolerance, which is a
feature of the natural and acquired immune system, the defect of which
leads to immune reactions against insiders and autoimmune diseases,
tolerance in both central and peripheral forms. And genes such as AIRE
have an effect on this mechanism (14, 15)
2. CTLA-4 receptor binds to the B7 receptor on APCs, preventing it from
binding to the CD28 stimulatory receptor and causing T lymphocyte
energy. Studies show that CTLA4 is impaired in lupus patients. (14)
3. Th2 cells play an important role in the production of antibodies by
acting on B lymphocytes. On the other hand, Th1 and Th2 cells have
inhibitory and controlling effects on each other through the cytokines
produced. Deviation and tendency towards (Th2 Skewing) has been observed
in lupus patients which has increased the level of immunoglobulin and
autoantibodies (16)
4. Any genetic disorder in the pathway of proteins of the internal and
external pathways of apoptosis, such as a disorder in the Fas-FasL
receptor that appears in the external pathway of apoptosis on T
lymphocytes and B lymphocytes, causes autoimmune diseases. (17)
5. BAFF (activating factor of B lymphocytes belonging to TNF family) is
one of the effective factors in the preservation and survival of B
lymphocytes and acts as a stimulator of B lymphocytes (BLYS) and can
stimulate the BAFF receptor, causing more activity. B lymphocytes. In
some patients with lupus, the level of BLYS is increased and its level
is associated with an increase in Anti-ds DNA titer (18)
6. Regulation of hemoral immune responses using specific FcγIIB receptor
on B lymphocytes as antibody feedback. Polymorphisms of this inhibitory
receptor are associated with autoimmune diseases such as SLE. (19)
7. Genetic defects of several complement proteins such as C1q, C2, C4
cause autoimmune diseases such as SLE due to lack of clearance of immune
complexes of circulating nuclear components and apoptotic components and
their deposition in tissues and the development of type allergies II and
III and tissue destruction (20)