Protecting us from the hazards of an infectious onslaught are our two formidable pillars of resistance, the innate and adaptive immune systems—complex networks both, whose continuous surveillance of our bodies’ inner workings would fill a National Security Agency analyst with envy. We can only look with wonder at the agility and elaborate plasticity of the human immune response.
But even this wonderful system can be prone to an occasional error, leading to the development of an infectious or an autoimmune disease. Sometimes, it may be due to a hardware issue, as in cases of immune deficiency where key components, such as serum immunoglobulins, may be lacking, or a selective complement component deficiency may predispose the bearer to lupus. In other situations, there may be a software glitch resulting in a misinterpretation of immune and infectious signals. One might consider the development of chronic fatigue following the supposedly successful treatment of B. Burgdorferi infection to be such an example. And in other cases, our immune defenses may have completely misunderstood the sequence of events, misinterpreting an infectious disease for an autoimmune disorder.
Mistaken Identity
A prime example of this sort of misunderstanding is the disease formerly known as essential mixed cryoglobulinemia (EMC). Aside from its chill-inspiring name that over the years has confused many well-intentioned medical house staff and students into believing that a patient’s freshly drawn blood sample needed to be cryopreserved immediately rather than spun and separated first, there was a long-held belief that this condition arose from some form of immune perturbation. Hence the appellation, essential, an oft-used medical term employed when we are clueless about the cause of a disease.
It had long been understood that cryoglobulin deposition spelled trouble because the inflammation caused by the plugging of vascular lumina often led to tissue ischemia downstream. Affected individuals developed an illness with overlapping features of lupus, vasculitis and rheumatoid arthritis (RA). Coupled with the observation that cryoglobulins often demonstrated the binding capabilities of rheumatoid factors (RFs), it was assumed that EMC was, at its core, an autoimmune disorder.
The innovative investigations of the late Ed Franklin, MD, formerly of New York University in New York City, along with his colleague, the late Henry Kunkel, MD, formerly of the Rockefeller University in New York City, established our core understanding of EMC. Their seminal research led to the characterization of EMC being associated with polyclonal IgG targeting RF-containing cryoglobulins (type II cryoglobulinemia).4 Although they suspected that a viral agent, such as hepatitis B virus, might be the driver of all this RF activity, there was scant evidence to support this view.
