**2. Autoantibodies in viral disease**

It is well established that there is often an association of transient, low-titer, polyspecific autoantibodies with common viral infections [6]. Autoantibodies may be detected in a variety of viral illnesses including hepatitis A, B, and C, parvovirus B19, enteroviruses, cytomegalovirus (CMV), and Epstein-Barr viruses (EBV) [1, 7–11]. Infectious agents have been implicated as an initial environmental trigger of AD in general, and in the induction of autoantibodies specifically [12–17]. It has been suggested that transient autoimmune responses are induced by acute viral infections in children and adults. Such responses may include generation of transient autoantibodies of typically low titer. The progression of such an immune state to an established autoimmune disease is rare [6, 18] as usually virally induced autoantibodies typically resolve with time. Hence, it may be difficult to differentiate autoimmune disease and self-limited illness.

Some of the commonly tested autoantibodies in viral infections include antinuclear antibodies (ANAs), antibodies directed against DNA, antibodies against proteins that bind to nucleic acids i.e. extractable nuclear antibodies (ENA), those directed against phospholipids, and antineutrophil cytoplasmic antibodies (ANCAs). In addition to these, the immune system may produce antibodies specific to certain tissues or organs (e.g., against hepatic, renal, gastric, intestinal, thyroid, pancreatic, muscular, testicular, dermatological, or neurological tissues). Also, the tendency of some viral infections to induce inflammatory responses in a variety of organ systems may also result in the development of autoimmune conditions. Hepatitis C and B virus, human immunodeficiency virus, parvovirus B19, cytomegalovirus, and Epstein-Barr virus appear to be associated with autoantibodies more commonly than other viruses.

### **2.1. Mechanism**

The mechanisms responsible for the generation of autoantibodies as a result of viral infections remain unclear. A few proposed mechanisms include cross-reactivity between viral proteins and autoantigens [19], molecular mimicry [16, 17, 20], and the induction of apoptosis of virusinfected cells [21], all leading to the production of autoantibodies. Another theory suggests that autoantibodies are anti-idiotypic antibodies to antiviral antibodies [22]. However, molecular or antigenic mimicry between microbial proteins and self-components (i.e., proteins, carbohydrates, or DNA epitopes) remains the most likely mechanism of autoimmunity post viral infection [20, 23].
