ABSTRACT
The descriptions of muscle pathology in dysferlinopathy patients have classically included an inflammatory infiltrate that can mimic inflammatory myopathies. Based on over 20 years of institutional experience in evaluating dystrophic and inflammatory myopathy muscle biopsies at the University of Iowa, we hypothesized the inflammatory histopathology of dysferlinopathy is more similar to limb-girdle pattern muscular dystrophies such as calpainopathy and Becker muscular dystrophy, and distinct from true inflammatory myopathies. Muscle biopsies from 32 dysferlinopathy, 30 calpainopathy, 30 Becker muscular dystrophy, and 30 inflammatory myopathies (15 each of dermatomyositis and inclusion body myositis) were analyzed through digital quantitation of CD3, CD4, CD8, CD20, and PU.1 immunostaining. The expression of MHC class I and deposition of complement C5b-9 was also evaluated. Dysferlinopathy, calpainopathy, and Becker muscular dystrophy muscle biopsies had similar numbers of inflammatory cell infiltrates and significantly fewer CD3+ T-lymphocytes than dermatomyositis (p = 0.05) and inclusion body myositis (p < 0.0001) biopsies. There was no statistically significant difference in the number of PU.1+ macrophages identified in any diagnostic group. MHC class I expression was significantly lower in the limb-girdle pattern muscular dystrophies compared to the inflammatory myopathies (p < 0.0001). In contrast, complement C5b-9 deposition was similar among dysferlinopathy, dermatomyositis, and inclusion body myositis biopsies but significantly greater than calpainopathy and Becker muscular dystrophy biopsies (p = 0.05). Compared to calpainopathy, Becker muscular dystrophy, and inflammatory myopathies, the unique profile of minimal inflammatory cell infiltrates, absent to focal MHC class I, and diffuse myofiber complement C5b-9 deposition is the pathologic signature of dysferlinopathy muscle biopsies.
Subject(s)
Inflammation/pathology , Muscular Dystrophies, Limb-Girdle/pathology , Muscular Dystrophy, Duchenne/pathology , Myositis/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
Chronic cardiopathy (CC) in Chagas disease is a fibrotic myocarditis with C5b-9 complement deposition. Mycoplasma and Chlamydia may interfere with the complement response. Proteolytic enzymes and archaeal genes that have been described in Trypanosoma cruzi may increase its virulence. Here we tested the hypothesis that different ratios of Mycoplasma, Chlamydia and archaeal organisms, which are frequent symbionts, may be associated with chagasic clinical forms. MATERIALS AND METHODS: eight indeterminate form (IF) and 20 CC chagasic endomyocardial biopsies were submitted to in situ hybridization, electron and immunoelectron microscopy and PCR techniques for detection of Mycoplasma pneumoniae (MP), Chlamydia pneumoniae(CP), C5b-9 and archaeal-like bodies. RESULTS: MP and CP-DNA were always present at lower levels in CC than in IF (p < 0.001) and were correlated with each other only in CC. Electron microscopy revealed Mycoplasma, Chlamydia and two types of archaeal-like bodies. One had electron dense lipid content (EDL) and was mainly present in IF. The other had electron lucent content (ELC) and was mainly present in CC. In this group, ELC correlated negatively with the other microbes and EDL and positively with C5b-9. The CC group was positive for Archaea and T. cruzi DNA. In conclusion, different amounts of Mycoplasma, Chlamydia and archaeal organisms may be implicated in complement activation and may have a role in Chagas disease outcome.
Subject(s)
Humans , Archaea/isolation & purification , Chagas Cardiomyopathy/microbiology , Chlamydophila pneumoniae/isolation & purification , Complement Membrane Attack Complex/analysis , Mycoplasma pneumoniae/isolation & purification , Antigens, Bacterial/analysis , Biopsy , Chronic Disease , Chagas Cardiomyopathy/pathology , In Situ Hybridization , Microscopy, Electron , Polymerase Chain ReactionABSTRACT
AIM: To explore the significance of measuring urinary complement C5b-9 complex in various types of immune complex (IC) nephritis models of rats. METHODS: The four models of rats, namely, passive Heymann nephritis (PHN), anti-thymocyte serum nephritis(ATSN), anti-glomerular basement membrane nephritis (AGBMN) and chronic serum disease nephritis (CSDN) were reproduced. Then, the contents of complement C5b-9 complex in plasma and urine of the rats were detected with sandwich ELISA. And the deposits of C5b-9 complex in glomeruli of the rats were examined by ABC immunohistochemistry staining. RESULTS: The contents of rat plasma C5b-9 were elevated and deposits of C5b-9 in glomeruli could be detected in the four model rats. But the increased urinary excretion of C5b-9 was observed only in PHN rats. Moreover, the time of urinary C5b-9 complex excretion was earlier than that of urinary protein in the rats with PHN. CONCLUSION: Urinary C5b-9 complex excretion could be taken as one of several sensitive immunologic parameters in diagnosing of PHN and in distinguishing PHN from other type of nephritis.