Whither smooth muscle antibodies in the third millennium?

Whither smooth muscle antibodies in the third millennium? Lupoid hepatitis (now known as autoimmune hepatitis type I) was defined as an autoimmune disease by Mackay and colleagues in 1965. 1 An immunological marker of the disease was identified by Johnson et al in 1965 in the form of an " antismooth muscle antibody ". 2 3 Over the following 30 years, smooth muscle antibody (SMA) has been used in the evaluation of patients with raised transaminases and has been given a defining role among diagnostic criteria for autoimmune hepatitis by the International Autoimmune Hepatitis Group. 4 Testing of these criteria on defined patient cohorts showed the criteria to be robust in defining autoimmune hepatitis. 5 Yet now, in the first year of the third millennium, SMA appears to have " fallen from grace ". Hepatologists are dismissing the test as useless (numerous personal communications), whereas others assert in an influential publication that they " do not recommend its routine use for the diagnosis of autoimmune hepatitis ". 6 As immunopathologists, we may well ask " what has hap-pened? ". The original description by Johnson et al of SMA in eight of 10 cases of " lupoid hepatitis " and in none of the 16 cases of systemic lupus erythematosus (SLE) provided a distinguishing marker between these two diseases, which shared the features of a positive lupus erythematosus (LE) test and a high concentration of serum globulin. 2 Whittingham et al then extended these observations to a larger number of individuals with lupoid hepatitis, of whom 26 of 32 were SMA positive, and demonstrated specificity by showing that this antibody was not detected in the serum of patients with SLE, other liver diseases, or healthy controls. 7 However, further studies indicated that SMA, albeit in low titre, could be detected in sera from normal individuals 8 and patients with a range of clinical problems including infections, 9 10 systemic autoimmune disease, 11 and cancer, 12 thus raising the issue of the specificity of SMA for autoim-mune hepatitis. The SMA reaction is now known to detect a range of cellular autoantigens in the cytoskeleton of smooth muscle and other cells. The cellular cytoskeleton consists of a family of filaments that are broadly classified by size into microfilaments (including actin and vinculin), intermediate filaments (including vimentin and desmin), and micro-tubules (tubulin). Autoantibodies to many of these proteins have been described but the SMA …