What do you propose are the major factors involved with the loss of tolerance?

loss of tolerance has been observed in STAT5A/5B deficient mice. STATs are signal transducers and activators of transcription.

Abnormal immune homeostasis (i.e. mechanisms of apoptosis, chronic inflammation etc.)

For genetically susceptible individuals it is most likely a combination of ag-specific and non-specific triggering events. Ag-specific events could be release of sequestered ag, presentation of cryptic epitopes or molecular mimicry. Non-specific (bystander) events may include infection by pathogens or exposure to other other environmental factors such as xenobiotics. Virus infections (single or sequential, heterologous) are prime candidates because they provide both, strong inflammation and ag-specific factors (i.e molecular mimicry as inducers or more likely as accelerators of a preexisting autoimmune condition).