PMC2841214_01
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.
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F1
She was subsequently hospitalized with pneumonia, and a third muscle biopsy performed during this hospitalization revealed chronic myopathic alterations associated with attenuated sarcolemmal dysferlin reactivity, consistent with limb girdle muscular dystrophy 2B (dysferlinopathy; Figure 1A).
PMC2841214_02
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.
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F2
A quadriceps muscle biopsy showed desmin-reactive hyaline bodies in the sarcoplasm of multiple myofibers, compatible with myofibrillar myopathy (Figure 2).
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.
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F3
The two MD patients clustered separately, suggesting different relatedness to SLE, with Patient 1 who had been thought to have had MCTD being more SLE-like (Figure 3). This analysis showed that IgG and IgA anti-gliadin were higher in both MD patients than in all but one of the 7 SLE patients (Figure 3).