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

MURDOCH RESEARCH REPOSITORYThis is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Abstract 1 Abstract 3 AbstractAlthough 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 biopsies from patients with suspected inflammatory myopathy. Positive MHC-I staining is nonspecific but is widely used as a marker for inflammatory myopathy, while the role of MHC-II staining is not clearly defined. We investigated the sensitivity and specificity of MHC-I and II immunostaining for the diagnosis of inflammatory myopathy in a large group of biopsies from a single reference laboratory. Positive staining for MHC-I was found to have a high sensitivity in biopsies from patients with inflammatory myopathy but a very low specificity, as it was also common in other non-inflammatory myopathies and neurogenic disorders.On the other hand, MHC-II positivity had a much higher specificity in all major subgroups of inflammatory myopathy, especially inclusion body myositis. The findings indicate that the combination of MHC-I and MHC-II staining results in a higher degree of specificity for the diagnosis of inflammatory myopathy and that in biopsies with inflammation, positive MHC-II staining strongly supports the diagnosis of an immunemediated myopathy. We recommend that immunohistochemical staining for both MHC-I and MHC-II should be included routinely in the diagnostic evaluation of muscle biopsies from patients with suspected inflammatory myopathy. However, as the sensitivity and interpretation of MHC staining may depend on the technique used, further studies are needed to compare procedures in different centres and develop standardised protocols.Abstract 4

Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies

“…Immunohistochemistry for MHC-1 and -2 has been known to be a useful pathological marker for IIM [16]. Especially MHC-1 is highly sensitive, albeit of low specificity.…”

Diagnostic criteria for inclusion body myositis

“…However, although sensitive, upregulation of MHC I lacks specificity and may be seen, presumably as a secondary phenomenon, in a wide range of noninflammatory myopathies. Possibly, MHC II may have greater specificity .…”

Sporadic inclusion body myositis: A review of recent clinical advances and current approaches to diagnosis and treatment

“…In an Australian study, in which home-based overnight polysomnography was performed, obstructive sleep apnoea was present in all 15 patients tested, even in patients without daytime respiratory symptoms, and was not correlated with the degree of limb muscle weakness (Rodriguez Cruz et al, 2014). Subclinical impairment of daytime ventilatory function, as shown by reduced vital capacity and nasal inspiratory pressures, was found in 75% of the cases.…”

“…Of these, p62 and TDP-43 are currently considered to be the most sensitive, although neither is specific for IBM. Upregulated expression of MHC-II antigens, in combination with MHC-I, has been shown to have a high specificity for IBM compared to MHC-I alone, and it has been recommended that both should be included routinely in the workup of biopsies from patients with a suspected inflammatory myopathy (Rodriguez Cruz et al, 2014). …”