Easy recognition and high autoimmune hepatitis specificity of smooth muscle antibodies giving an actin microfilament immunofluorescent pattern on embryonal vascular smooth muscle cells.

Smooth muscle antibodies (SMA) with anti-microfilament actin (MF-SMA) specificity are regarded as highly specific markers of type 1 autoimmune hepatitis (AIH-1) but their recognition relying on immunofluorescence of vessel, glomeruli, and tubules (SMA-VGT pattern) in rodent kidney-tissue, is restricted by operator-dependent interpretation.A gold standard method for their identification is not available. We assessed and compared the diagnostic accuracy for AIH-1 of an embryonal-aorta vascular-smooth-muscle(VSM) cell line-based assay with those of the rodent-tissue based assay for the detection of MF-SMA pattern in AIH-1 patients and controls. Sera from 138 AIH-1 patients and 295 controls (105 primary biliary cholangitis,40 primary sclerosing cholangitis,50 chronic viral hepatitis,20 alcohol-related liver disease,40 steatotic liver disease,and 40 healthy controls) were assayed for MF-SMA and for SMA-VGT using VSM-based and rodent tissue-based assays, respectively. MF-SMA and SMA-VGT were found in 96(70%) and 87(63%) AIH-1 patients, and 2 controls (p<0.0001).Compared with SMA-VGT, MF-SMA showed similar specificity (99%), higher sensitivity (70% vs 63%,p=ns) and likelihood ratio for a positive test (70 vs 65). Nine (7%) AIH-1 patients were MF-SMA positive despite being SMA-VGT negative. Overall agreement between SMA-VGT and MF-SMA was 87% (kappa coefficient 0.870,[0.789-0.952]). MF-SMA were associated with higher serum γ-globulin [26(12-55) vs 20 g/l(13-34),p<0.005] and immunoglobulin G (IgG) levels [3155(1296-7344) vs 2050 mg/dl(1377-3357), p<0.002]. The easily recognizable IFL MF-SMA pattern on VSM cells strongly correlated with SMA-VGT and has an equally high specificity for AIH-1. Confirmation of these results in other laboratories would support the clinical application of the VSM cell-based assay for reliable detection of AIH-specific SMA.