Figure 1.

Immunogenetic mechanisms of dual autoimmunity. Coexistence of two autoimmune disorders in the same patient may occur due to multiple mechanisms. Schematic representation of the potential pathways leading to the induction of PV and MCTD is shown on the three panels. Based on the assumption that production of autoantibodies is triggered by T cells interacting with the autoantigenic epitopes bound to the susceptible HLA alleles, the following scenarios are described: 1 (left panel, Single HLA recognition). In this case, each T cell epitope specific for a single disease may associate with its susceptible HLA protein, leading to T cell activation and subsequent stimulation of B cells to produce autoantibodies, which would result in dual autoimmunity. 2 (central panel, Dual HLA Recognition). Here, each of the disease-specific autoantigens may bind to either HLA protein, leading to the induction of both diseases by cross-presentation. 3 (right panel, Dual HLA Recognition). According to this scenario, two distinct epitopes of the same autoantigen may be able to bind two disease-associated HLA molecules. Similar pathways would apply to the situation when MCTD and MMP are presented in the same patient.