Autoantibody profiles in two patients with non-autoimmune muscle disease implicate a role for gliadin autoreactivity

Abstract

The objective of this case study was to characterize autoreactivity in two patients with non-autoimmune forms of muscle disease who had positivity for antinuclear antibodies (ANA) and Ro (SSA) autoantibodies. Serum samples from these two patients were applied to an autoantigen protein array with more than 70 specificities and were compared to samples from healthy controls and patients with systemic lupus erythematosus. Both myopathy patients had high levels of gliadin autoreactivity in serum and one patient had an overall autoantibody profile with lupus-like features. The findings suggest that some disorders of muscle that are considered non-autoimmune, may in fact have autoimmune features. Further examination of the role of subclinical gluten autoreactivity in the pathogenesis of myopathy syndromes has the potential to suggest improved approaches to diagnosis and treatment of these conditions.

Figure 1

Quadriceps muscle biopsy from Patient 1. The H&E stain (panel A, left) reveals abnormal fiber size variability, accompanied by a spectrum of chronic myopathic changes including occasional degenerating and regenerating fibers and mildly increased numbers of internalized nuclei. Increased adipose tissue also was noted. No inflammatory infiltrates were present. Immunohistochemical staining for dysferlin (panel B, right) reveals attenuated and/or discontinuous sarcolemmal reactivity in a significant number of myofibers (arrows) (Dysferlin, Novocastra, Newcastle Upon Tyne, UK). Magnification 200x.

Figure 2

Quadriceps muscle biopsy from Patient 2. The H&E stain (panel A, top left) shows fiber size variability, accompanied by the presence of well-developed sarcoplasmic hyaline inclusions in a significant minority of myofibers (arrows). The inclusions stain dark blue in the Gomori trichrome stain (panel B, top right, arrows), and are desmin-reactive (panel C, lower left, arrows) (Desmin, Dako, Carpenteria, CA, USA). Many of the hyaline deposits are associated with a peripheral rim of dystrophin reactivity (panel D, lower right, arrows) (Dystrophin rod domain, Novocastra, Newcastle Upon Tyne, UK). Magnification 200x.

Figure 3

Clustering analysis of IgG autoantibody profiles measured on the autoantigen array in 7 healthy controls (HC), 7 SLE patients and 2 muscle disease (MD) patients (left panel). Each row represents one autoantibody specificity and each column represents an individual sample. The top row indicates mean IgG expression for all specificities in each individual subject. The normalized signal intensity of each antibody was analyzed using Cluster/Treeview software and the two clusters generated are outlined in blue and the two MD patients are indicated by yellow ovals. Red represents expression values higher than the row median, green represents expression values lower than the row median and black represents values close to the row median. The left cluster contains 5 of the HC and MD Patient 2. The right cluster contains all of the SLE patients as well as 2 HC and MD Patient 1. Expression levels of autoantibodies in the three subject groups (Right panel). Gliadin IgG and IgA levels are higher than in all but one of the 7 SLE patients (top row) and similar results are observed for IgG and IgM C1q antibodies (middle row). RoSSA L(60Kd) IgG was increased in MD patients compared to HC (bottom left) while IgG myosin antibodies were generally lower in the MD patients (bottom right). For each group, horizontal line indicates mean values; for HC and SLE groups, error bars indicating SEM values are also shown.