Autoimmunity is a biological betrayal. Your immune system is there to defend you against outsiders (to wit: viral, bacterial, fungal or protozoan pathogens) and to weed out cancer cells before they become tumors. Yet in rheumatoid arthritis, type-1 diabetes and multiple sclerosis, to name a few of the most well known autoimmune diseases, immune soldiers called T cells turn on one or another of your own tissues and launch increasingly vicious aberrant assaults on it.
Nobody’s sure exactly what causes any of these disparate disorders, although combinations of inherited susceptibility and environmental triggers surely loom large as contributors.
In a new study in the Journal of Experimental Medicine, Stanford rheumatologists Connie Weyand, MD, and Jorg Goronzy, MD, and their colleagues have fingered a particular metabolic defect that appears to be specific to rheumatoid arthritis. T cells have an odd job description, which calls for them to mostly sit around and spend their lives loafing but, as soon as they recognize – or get a bit trigger-happy and think they recognize – a foreign intruder, to spring into action, multiplying and morphing as they do.
Both of those activities take a lot more energy than a T cell in its lazy laid-back-little-loafer lifestyle would have ever dreamed of expending. Nature doth provide, of course, and over the eons our T-cells have evolved (along with other fast-dividing cells) a special metabolic procedure that lets them ramp up their conversion of glucose to energy or to raw materials for making important biomolecules they’ll need in order to work much harder and replicate more rapidly than ordinary cells under ordinary conditions.
Weyand, Goronzy and their team found, in T cells taken from rheumatoid arthritis patients, an apparently intrinsic deficiency in that alternate glucose-conversion operation. As a result, attempts on the part of T cells in the patients’ bodies to cope with environmental insults can cause these cells to burn out and collapse in a fit of exhaustion.
Somewhat paradoxically, it may be the demise of these cellular spent forces that trips off the symptom-generating aspect of rheumatoid arthritis. Weyand suspects that immune tries to counter the chronic loss and growing dearth of relevant T cells by producing ever new batches of them – until, in its haste, it mistakenly produces some that are reactive to joint tissue.
Examination of T cells drawn from patients with another autoimmune disease, lupus, revealed no signs of this defect, which may turn out to be a uniquely predisposing factor for rheumatoid arthritis. (A prematurely aged immune system is one of this disease’s hallmark features.) Because the defect is present long before symptoms develop, it could turn out to be a biomarker for rheumatoid arthritis, giving physicians a leg up on diagnosing people at risk for developing the syndrome.