Pathophysiology Pathophysiology

Environmental factors serve as triggering agents for Lupus in genetically and hormonally susceptible individuals. They induce a state of immune dysregulation, and lead to hyperactive T-helper type 2 lymphocyte and Blymphocyte function.

Hyperactive B lymphocytes leads to excessive autoantibody production, and Immune regulatory mechanisms whose function is to downregulate autoantibody formation and suppress T-lymphocyte function, fail, which leads to excessive cytokine production and no suppression of autoantibody production.

The autoantibodies formed become pathogenic and form immune complexes that damage host tissue.

Multiple mechanisms to B-cell hyperactivity take place:

Loss of immune “self” tolerance

High antigenic load; environmental and self-antigens presented to B cells by other B cells or specific APC

Defective T-helper cells that increase B-cell antibody production and decrease defective B-cell clearance

Impairment of other immune regulatory processes including suppressor T cells function, cytokines (interleukins, interferon-γ, TNF-α, transforming growth factor-β)

Autoantibodies are directed against nuclear constituents of the cell and are thus called antinuclear antibodies. Lupus patients may have more than one antigenspecific antinuclear antibody: dsDNA and ssDNA: Antibodies to dsDNA are highly specific for Lupus and are present in 70% to 80% of patients.

RNA-associated antigens: Four RNA-associated antigens exist; the Smith (Sm) antigen, the small nuclear ribonucleoprotein (snRNP), the Ro (SS-A) antigen and the La (SS-B) antigen.

Histone: A basic component of chromatin and nucleosomes.

Lupus anticoagulant: The phospholipid moiety of the prothrombin activator complex.

Cardiolipin