Systemic lupus erythematosus in the elderly

Aging modifies the clinical presentation and course of autoimmune disorders, although the mechanisms by which this occurs remain to be determined. Current evidence cited above supports the general concept that there is a natural senescence of the immune system. This evidence would suggest that somehow senescence directly affects gene expression, resulting in biochemical abnormalities that culminate in T-cell immunodysfunctions. This may be a principal factor that attenuates the autoimmune response to self-antigen and, therefore, the disease course. The authors speculate that there is a disorder primary to the T cell in SLE that is expressed as abnormal immunologic responses to self-antigens, resulting in autoimmunity. Although understanding of this primary T cell disorder is still limited, clinicians now know that the T cell harbors abnormal signaling pathways that reflect defective biochemical functions and seem to be genetically regulated. This aberrant signaling would be anticipated to affect both principal T cell subsets. It may hinder the capacity of cells, such as CD8 T cells, to effectively down-regulate the response of autoreactive CD4 helper T cells to autoantigens. Loss of self-regulation would manifest itself as loss of tolerance, a fundamental component of autoimmunity. The future challenge is to understand how aberrant signaling leads to loss of tolerance. Given this underlying genetic susceptibility in an aged individual whose T cells also are undergoing natural senescence, the authors suggest that it is conceivable that a stress factor may tip the balance in the favor of clinical disease. One such factor may be unspecified environmental stimuli. Yet another consideration is an intercurrent illness, such as an infection. It remains to be determined, however, what these environmental stimuli are and how they impact on the immune system to trigger disease.