Infection, mimics, and autoimmune disease.

observation that infection can precipitate an autoimmune disease dates back more than a century. The first human autoimmune disease described, paroxysmal cold hemoglobulinuria, was thought of as a late consequence of syphilis, and rheumatic fever is still associated with preceding streptococcal infection. In modern times, these associations have been attributed to molecular mimicry. In its simplest form, the concept of molecular mimicry states that antigenic determinants of infectious microorganisms resemble structures in the tissues of the host but differ enough to be recognized as foreign by the host's immune system. It is now clear that mimicry on the molecular level is a common phenomenon; that is, many sequential and structural determinants of infectious agents simulate epitopes of host tissues (1). But, as Mackay and I remarked recently, " There are, as yet, no firm instances of molecular mimicry by microorganisms serving as initiating agents of human autoim-mune disease… " (2). There is probably no better candidate for investigating mimicry than the car-diomyopathy of chronic Chagas' disease. It afflicts about 30% of the 20 million individuals infected with the protozoan Trypanosoma cruzi in the Americas. The presence of a cardiac inflammatory infiltrate in apparent absence of parasites suggests that the trypanosome initiates an autoimmune response. Indeed, a number of cross-reactive human antigens have been implicated by their reaction with sera of Chagas patients. They include, for example, a 23 kDa ribosomal protein (3), a functional epitope on the β 1 adren-ergic receptor (4), a 48 kDa protein found in neuronal axons (5), and a hep-tapeptide of cardiac myosin heavy chain (6). In this issue of the JCI, Gironès and colleagues have identified another cross-reactive antigen (Cha), a novel peptide from human cells (7). This peptide, which reacts with the sera of patients with chronic Chagas' disease and of mice infected with T. cruzi, was found in abundance in human and mouse hearts. Cross-reaction between the mammalian and trypanosomal peptides was documented for both T and B cells. The finding that this peptide bears both Band T-cell epitopes makes it a leading candidate for the induction of the car-diomegaly of Chagas' disease through molecular mimicry, since it would facilitate T/B-cell cooperation (8). This work leaves critical questions unanswered. Some patients with Cha-gas' disease develop megacolon and megaesophagus due to destruction of parasympathetic ganglia, but Cha is not found in nervous tissue. No functional changes were associated with Cha-specific antibodies. On the other …