G.P.79: An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies

Abstract

Although there have been several previous reports of immunohistochemical staining for MHC antigens in muscle biopsies, there appears to be a lack of consensus about its routine use in the diagnostic evaluation of patients with suspected inflammatory myopathy (IM). Positive MHC-I staining is non-specific but is widely used as a marker for IM, while the role of MHC-II staining is not clearly defined. We investigated the sensitivity and specificity of MHC-I and II for the diagnosis of IIM in 432 biopsies from a single reference laboratory (186 cases of IIM and 246 cases of non-inflammatory myopathies (NIM) and other neuromuscular disorders). MHC-I showed a very high sensitivity (0.984) in patients with IM and very low specificity (0.071). On the other hand, MHC-II showed a high specificity (0.908) and moderate sensitivity (0.605) in all major subgroups of IM especially inclusion body myositis. When only MHC-I was taken into consideration, the area under the ROC curve was 0.53 and increased to 0.762 (SE: 0.024; <i>p</i><0.001) when MHC-II staining was added. In the IM group there was a significant association between MHC-II positivity and infiltrates (<i>p</i>=0.014). The findings indicate that the combination of MHC-I and MHC-II staining results in a higher degree of specificity for the diagnosis of IM and that in biopsies with inflammation, positive MHC-II staining strongly supports the diagnosis of an immune-mediated myopathy. We recommend that immunohistochemical staining for both MHC-I and MHC-II should be included routinely in the evaluation of muscle biopsies from patients with suspected IM. However, as the interpretation of MHC staining is very dependent on the technique used, further studies are needed to compare procedures in different centres and develop standardised protocols.