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PubMed2000

Mitochondrial DNA variants in inclusion body myositis.

Mitochondrial DNA variants have been shown to be associated with many diseases. Mutations at mitochondrial DNA nucleotide positions 3192, 3196, 3397 and 4336 have been described in association with late-onset Alzheimer's disease. The pathological similarities between inclusion body myositis and Alzheimer's disease prompted an analysis of the relationship between the reported mutations and sporadic inclusion body myositis. The 4336G variant was not significantly increased in patients with inclusion body myositis or Alzheimer's disease when compared to controls. None of the patients with inclusion body myositis carried mutations at nucleotide positions 3192, 3196 and 3397. A transition at nucleotide position 4580 was detected in some patients with inclusion body myositis and Alzheimer's disease but was not significantly higher in frequency when compared to controls. Phylogenetic analysis showed that the 4336G and 4580A variants clustered together in their respective group. A group of patients with inclusion body myositis also clustered together on a separate branch of the phylogenetic tree. Closer investigation of this group revealed a common polymorphism at nucleotide position 16311. The frequency of the 16311C variant was higher in inclusion body myositis than in Alzheimer's disease and controls, although when only caucasian patients were considered the increased frequency was not statistically significant. Further studies will be required to determine whether this variant plays a role in the pathogenesis of inclusion body myositis.

Adult↗
PubMed1993

Autoantibodies in myositis.

Several autoantibodies are found specifically in myositis. Mostly this is myositis in the context of a connective tissue disease with associated features such as Raynaud's phenomenon, arthralgias, pulmonary fibrosis or scleroderma. The patterns of disease amount to overlap syndromes or subsets in which one can often predict the presence of a particular type of autoantibody. There are HLA associations, particularly with DQ alleles, related more closely to the antibody than to myositis overall. There is also a suggestion of seasonal and geographical variation within the United States distinguishing the advent of particular autoantibodies with the myositis. The myositis antigens are mainly ribonucleoprotein particles (RNA-protein complexes) functioning in RNA processing, protein translation and protein translocation into the endoplasmic reticulum. Within the cell the antigens are not accessible to antibody, with the possible exception that antibody to U(1)RNP may enter cells. If antibodies are to have a role in pathogenesis it is more likely to be through binding to cell membranes (there to activate complement or mediate T lymphocyte activity) or through immune complex mechanisms. The myositis antigen Ku has been detected on cell membranes, but generally in myositis there is scant deposition of immunoglobulin or complement in muscle except within small blood vessels. If autoantibodies really have little part to play in the pathogenesis of myositis their existence must relate to the earlier events of aetiology, like fingerprints on fragments of a terrorist's bomb.

Autoantibodies↗
PubMed1996

Dermatomyositis sine myositis: association with malignancy.

OBJECTIVE: To describe dermatomyositis (DM) sine myositis as a distinct diagnostic subclass of DM and the association with malignancy. METHODS: This case series includes all patients presenting to our primary and tertiary care outpatient dermatology department with DM and DM sine myositis between 1986 and 1993. Seven patients were diagnosed with classic DM and 12 with DM sine myositis. We analyzed average age of onset, duration of followup, clinical course, and incidence of associated malignancy in the patients with classic DM and DM sine myositis. RESULTS: No statistically significant differences were found in these 2 groups on examining age at onset and frequency of associated malignancy. Malignancy was diagnosed in 4 of 12 (25%) patients with DM sine myositis followed for a total of 50.8 patient-years (average followup 51 months) and in 2 of 7 (28%) patients with classic DM followed for a total of 20.6 patient-years (average followup 35 months). CONCLUSION: Although these patients with DM are select and few, they demonstrate that DM sine myositis may be quite similar to classic DM. It may be said that like DM, DM sine myositis may represent a paraneoplastic syndrome. DM sine myositis should be added to the currently accepted polymyositis/dermatomyositis classification system, with appropriate emphasis on the potential association with malignancy.

Adult↗
PubMed2003

Orbital myositis in scleritis.

AIMS: To investigate the association between scleritis and myositis. METHODS: Retrospective, non-comparative case series. Records and ultrasonograms were examined of 132 patients, with a diagnosis of episcleritis or scleritis, who attended the ophthalmology department at Leiden University Medical Center between 1997 and 2000. 103 were eligible for comprehensive examination. Medical records were evaluated. Ultrasonography was performed in all patients diagnosed with episcleritis or scleritis. Clinical features, precipitating factors, systemic associations, ocular complications, treatment, and outcome of each patient were assessed. RESULTS: Of the 103 patients, 27 (26.2%) had episcleritis and 76 (73.8%) had scleritis. Myositis was found to be present in 11 patients. It was present in 14.5% of all patients with scleritis and 30.5% of those in whom the posterior sclera was affected. The presence of the associated myositis did not worsen the visual prognosis and the presence of myositis was not associated with other systemic diseases. There were no cases of unilateral scleritis with bilateral orbital myositis. During an attack ocular complications were more common in patients with scleritis and myositis (64%) than in patients with scleritis alone (30.4%), indicating a more diffuse and potentially dangerous inflammation. There was no evidence that the inflammatory changes in the orbit had spread to involve the sclera, so it is assumed that the muscle changes are an extension of a generalised response to intense inflammation of the episclera and sclera. CONCLUSION: This study found a frequent association between myositis and scleritis. Prognosis for vision was not affected by coexistence of myositis.

Adult↗
PubMed2000

Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia.

BACKGROUND: About 50% of patients with thymoma have paraneoplastic myasthenia gravis (MG). Myositis and myocarditis or neuromyotonia (NMT) will also develop in some. Patients with thymoma-associated MG produce autoantibodies to a variety of neuromuscular antigens, particularly acetylcholine receptor (AChR), titin, skeletal muscle calcium release channel (ryanodine receptor [RyR]), and voltage-gated potassium channels (VGKC). OBJECTIVE: To examine whether neuromuscular autoantibodies in patients with thymoma correlate with specific clinical syndromes. METHODS: Serum and plasma samples from 19 patients with thymoma-associated MG, of whom 5 had myositis and 6 had NMT, underwent testing for antibodies to AChR, titin, RyR, and VGKC. RESULTS: Antibodies to AChR and titin were found in 19 and 17 patients, respectively. Antibodies to RyR correlated with the presence of myositis (P = .03); they were found in all 5 patients with myositis and in only 1 patient with NMT, but also in 4 of 8 patients with neither disease. Antibodies to VGKC were found in 4 patients with NMT, 1 of 3 patients undergoing testing for myositis, and 2 of 7 patients undergoing testing with neither comorbidity. Presence of RyR antibodies correlated with high levels of titin antibodies. CONCLUSIONS: The results appear to distinguish partially between 3 groups of patients with thymoma-associated MG: the first with RyR antibodies and myositis or myocarditis, the second with NMT without RyR antibodies, and the third without RyR antibodies, myositis, or NMT. Differences in the thymoma may underlie these pathologic associations.

Adult↗
PubMed2005

Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction.

OBJECTIVE: The etiology and pathogenesis of human inflammatory myopathies remain unclear. Findings of several studies suggest that the degree of inflammation does not correlate consistently with the severity of clinical disease or of structural changes in the muscle fibers, indicating that nonimmune pathways may contribute to the pathogenesis of myositis. This study was undertaken to investigate these pathways in myositis patients and in a class I major histocompatibility complex (MHC)-transgenic mouse model of myositis. METHODS: We examined muscle tissue from human myositis patients and from class I MHC-transgenic mice for nonimmune pathways, using biochemical, immunohistochemical, and gene expression profiling assays. RESULTS: Up-regulation of class I MHC in skeletal muscle fibers was an early and consistent feature of human inflammatory myopathies. Class I MHC staining in muscle fibers of myositis patients showed both cell surface and a reticular pattern of internal reactivity. The pathways of endoplasmic reticulum (ER) stress response, the unfolded protein response (glucose-regulated protein 78 pathway), and the ER overload response (NF-kappaB pathway) were significantly activated in muscle tissue of human myositis patients and in the mouse model. Ectopic expression of wild-type mouse class I MHC (H-2K(b)) but not degradable glycosylation mutants of H-2K(b) induced ER stress response in C(2)C(12) skeletal muscle cells. CONCLUSION: These results indicate that the ER stress response may be a major nonimmune mechanism responsible for skeletal muscle damage and dysfunction in autoimmune myositis. Strategies to interfere with this pathway may have therapeutic value in patients with this disease.

Animals↗
PubMed2005

Role of major histocompatibility complex class I molecules in autoimmune myositis.

PURPOSE OF REVIEW: Recent work has continued to clarify the role of major histocompatibility complex class I in the pathogenesis of autoimmune myositis. In the past year, several new observations have been made in this area. This review describes these findings and discusses their relevance to the pathogenesis of autoimmune myositis. RECENT FINDINGS: Recent studies have confirmed earlier observations of the up-regulation of major histocompatibility complex class I antigens in myositis. In particular, a recent study has strengthened the conclusion that major histocompatibility complex class I expression is highly specific to inflammatory myopathies and may be of diagnostic value. Two new studies have indicated that endoplasmic reticulum stress response pathway (the endoplasmic reticulum overload [NF-kB] and unfolded protein response [GRP78]) are highly activated in patients with myositis. One study using transgenic mice has further indicated that abnormal accumulation of major histocompatibility complex class I in the endoplasmic reticulum of muscle may be responsible for the initiation of this endoplasmic reticulum stress response. Furthermore, studies of normal muscle cells have shown that endoplasmic reticulum stress also plays an important role in skeletal muscle development. Investigations of autoantigen expression in myositis biopsies have revealed that regenerating muscle cells express high levels of autoantigens and major histocompatibility complex class I, indicating that these cells are the targets of cytotoxic T-cell attack and may participate in the initiation of a myositis-specific autoimmune response. SUMMARY: Defining the role of major histocompatibility complex class I in autoimmune myositis may be useful not only for diagnosis of this group of diseases but also for therapeutic opportunities for these difficult disorders.

Animals↗
PubMedDate not supplied

A comparative study of outcome in myositis and other musculoskeletal disorders assessed using the Nottingham health profile.

OBJECTIVE: This study evaluated the comparative impact of myositis and other musculoskeletal disorders on general health using the Nottingham health profile (NHP) as a generic measure of health status. METHODS: A prospective observational study of 113 females with myositis, 142 females with rheumatoid arthritis, 45 females with spinal osteoporosis and 96 females with knee osteoarthritis. RESULTS: All mean NHP section scores were higher in myositis and other musculoskeletal disorders compared to population mean values. Section scores for energy and social isolation were high in myositis compared to all other disorders. Scores for physical disability in myositis were similar to RA. Pain scores were higher in RA and OA compared to myositis. Backwards linear regression models explained 26-42% of the variation in energy and social isolation scores. Emotion and physical section scores were the major determinants and the pattern was similar in all disorders. Disease duration and age had little effect. CONCLUSIONS: Myositis is not simply a disease with physical problems but has wide ranging effects on social and emotional well being. Until disease-specific instruments are available, a generic measure like the NHP can be used to assess problems other than muscle pain and loss of strength.

Activities of Daily Living↗
PubMed2004

Muscle and brain changes of calcitonin gene-related peptide in experimentally induced unilateral rat masseter myositis.

AIMS: To investigate changes in calcitonin gene-related peptide (CGRP)-like immunoreactivity (CGRP-LI) in the rat masseter muscle and brain after the unilateral experimental induction of masseter myositis. METHODS: Ipsilateral and contralateral changes of the CGRP were examined in rat masseter muscle after the induction of unilateral myositis on the right side with an intramuscular injection of 0.01 mL Freund's adjuvant. The left masseter, and left and right masseters of control rats, were injected with 0.01 mL saline (0.9%). After 21 days, tissue samples from the masseter muscles and the hypothalamic-pituitary-adrenal (HPA) axis were analyzed for the presence of CGRP by immunohistochemistry, radioactive immunoassay, and high performance liquid chromatography. Hematoxylin-eosin staining was used to confirm inflammation in the masseter muscles. RESULTS: Elevated CGRP-LI was detected bilaterally in the masseter muscles (P < .001) in the myositis group. CGRP-immunoreactive nerve fibers were mainly detected in close proximity to muscle cells and in the walls of the blood vessels. Compared to the control rats, a significant difference in scratching behavior was seen in the myositis group from day 9 until day 21. In the myositis group, CGRP-LI was increased in the pituitary gland concomitant with the increase in CGRP-LI in the masseter muscles but was decreased in the hypothalamus. A possible explanation for these changes could be that rats with chronic myositis develop an abnormal function of the HPA axis triggered by masseter muscle inflammation. CONCLUSION: The results of this study demonstrate that CGRP may play an important role both peripherally and centrally in masseter muscle myositis in association with presumed nociceptive behavior.

Animals↗
PubMed2004

Myositis specific autoantibodies: changing insights in pathophysiology and clinical associations.

PURPOSE OF REVIEW: Defined autoantibodies are found in about half of the patients with myositis. Traditionally, these autoantibodies have been divided into myositis specific autoantibodies (MSAs) and myositis associated autoantibodies. Several studies have shown that MSAs are associated with specific clinical characteristics and can aid our understanding of the pathophysiology of myositis. RECENT FINDINGS: Recent studies suggest that some MSAs are markers of specific inflammatory muscle diseases (e.g., anti-SRP for an immune-mediated necrotizing myopathy) and not just of myositis in general. Furthermore, new insights are emerging about the pathophysiology of MSAs, in particular anti-Jo-1. Based on these new insights, an alternative hypothesis of the formation of anti-Jo-1 autoantibodies is presented in which the immune system itself rather than muscle is the site of antigen presentation. SUMMARY: The recognition that some MSAs are markers of specific disease entities that were once commonly referred to as (poly)myositis, aids the development of better disease definitions. The changing insights in the function of the Jo-1 antigen and the emergence of new hypotheses on the formation of the Jo-1 antibody, open new avenues for future research aimed at unraveling the mystery of myositis.

Antibody Specificity↗
PubMed2005

Pathologic skeletal muscle perfusion in patients with myositis: detection with quantitative contrast-enhanced US--initial results.

PURPOSE: To prospectively determine whether contrast material-enhanced ultrasonography (US) can depict inflammation-induced changes in muscle perfusion for patients suspected of having dermatomyositis or polymyositis and to compare these findings with those of magnetic resonance (MR) imaging and muscle biopsy. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Perfusion in skeletal muscles was quantified with contrast-enhanced intermittent power Doppler US by applying a modified model that analyzed the replenishment kinetics of microbubbles. In 22 patients (16 women, six men; mean age, 52 years +/- 17) who were suspected of having myositis and in 10 healthy volunteers (two women, eight men; mean age, 28 years +/- 4), contrast-enhanced US of the clinically affected right biceps muscle was performed to measure blood flow, blood volume, and blood flow velocity. Additionally, the right upper arm was examined with a 1.5-T unit by using three different MR imaging techniques. Findings were compared with the results of clinical examinations and muscle biopsy. Data for perfusion-related parameters obtained at contrast-enhanced US were analyzed by using a nonparametric Mann-Whitney U test. RESULTS: Eight patients had histologically confirmed myositis and showed significantly higher blood flow velocity (P = .01), blood flow (P = .001), and blood volume (P = .002) at contrast-enhanced US than did patients who did not have myositis. Blood flow velocity (P = .001) and blood flow (P = .002) were significantly higher in patients with myositis than in volunteers. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis, while contrast material enhancement on fat-suppressed T1-weighted MR images was found in only four of seven patients with myositis. CONCLUSION: Initial results show that contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups in patients with myositis.

Biopsy↗
PubMed2004

International consensus on preliminary definitions of improvement in adult and juvenile myositis.

OBJECTIVE: To use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials. METHODS: Twenty-nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty-seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data-mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top-performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were >/=75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation. RESULTS: The definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by >/=20%, with no more than 2 worse by >/=25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials. CONCLUSION: Consensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials.

Adult↗
PubMed2004

Immunogenetic differences between Caucasian women with and those without silicone implants in whom myositis develops.

OBJECTIVE: To determine whether patients in whom myositis develops after they receive silicone breast implants have distinct clinical, serologic, and/or immunogenetic features compared with patients with myositis who do not have silicone implants. METHODS: A preliminary case series study was followed by a larger, independent, matched case-control study to evaluate women in whom myositis developed after they received silicone implants (MASI patients) compared with healthy women with silicone implants and women with myositis but without silicone implants (idiopathic inflammatory myopathy; IIM patients). RESULTS: In a preliminary study, 11 MASI patients differed from 76 IIM patients in having an increased frequency of HLA-DQA1*0102 (odds ratio [OR] 9.8, 95% confidence interval [95% CI] 1.77-96.79) and decreased frequencies of the myositis-associated risk factor DRB1*0301 (OR 0.1 [95% CI 0.002-0.63]) and its linked allele DQA1*0501 (OR 0.2 [95% CI 0.02-0.87]). A subsequent independent, matched case-control study revealed that although clinical features and autoantibodies did not differ significantly between the MASI and IIM groups, MASI patients again had decreased frequencies of DRB1*0301 (OR 0.2 [95% CI 0.07-0.72]) and DQA1*0501 (OR 0.2 [95% CI 0.08-0.84]) compared with IIM patients. Additional comparisons between MASI patients from both studies combined (n = 37) and a larger population of IIM patients (n = 453) suggested that HLA-DQA1*0102 may be uniquely associated with MASI (OR 2.6 [95% CI 1.25-5.46]). CONCLUSION: Women in whom inflammatory myopathy develops after they receive silicone implants constitute an immunogenetically distinct group of patients with myositis. These and other data suggest that autoimmune diseases as now defined may consist of multiple distinct entities, each of which is characterized by different genes and environmental exposures.

Adult↗
PubMed2005

[Inflammatory muscle diseases: dermatomyositis, polymyositis, and inclusion body myositis].

Dermatomyositis, polymyositis, inclusion body myositis and myositis overlap syndromes are systemic immune disorders of unknown origin with muscle weakness and elevated values of creatinkinase in the serum. Muscle biopsy is pivotal for a proper clinical diagnosis. Extramuscular findings at the skin, the joints or internal organs (lung, heart) are characteristic for the different clinical presentations of dermato- or polymyositis and are usually absent in inclusion body myositis. With the exception of inclusion body myositis myositis-associated autoantibodies are frequently present and associated with distinct clinical manifestations (e. g. antisynthetase syndrome). The rate of malignancy is elevated for several years after onset of myositis. Especially in polymyositis an appropriate differential diagnosis of infectious, endocrine, metabolic or neuromuscular causes of muscle disease is necessary. Glucocorticosteroids are the first choice of treatment in dermato- or polymyositis. Methotraxate, azathioprine, cyclophosphamamide, i.v. immunoglobulins and other drugs are used in diseases courses with continuous high dose requirement of corticosteroids.

Adrenal Cortex Hormones↗
PubMed2003

Defining Clinical Improvement in Adult and Juvenile Myositis.

The lack of consensus regarding outcome measures and trial design issues in the idiopathic inflammatory myopathies (IIM) is inhibiting the conduct and interpretation of clinical trials. To begin to address these problems, a multispecialty group of over 70 adult and pediatric neurologists, rheumatologists, rehabilitation medicine physicians, statisticians, and patient support group leaders, called the International Myositis Outcome Assessment Collaborative Study Group (IMACS), is engaged in developing consensus on the assessment of disease activity and damage for myositis clinical trials. As part of this ongoing international effort, members of this group met in November 2001 at a work-shop entitled "Defining Clinical Improvement in Adult and Juvenile Myositis." A goal of the work-shop was to review current data on the validity and responsiveness of the recently published proposed preliminary core set measures for disease outcome assessment in clinical trials for myositis and to define the degree of change in each core set measure that is clinically meaningful. Despite differences in the clinical presentations, natural history and responses to therapy between adult onset and juvenile onset myositis, expert specialists in these diseases came to a consensus that the amount of improvement that is clinically meaningful in each core measure is the same for adult and juvenile myositis. For the domains of muscle strength and physical function, a minimum of 15% improvement is clinically significant, whereas for the physician and patient global assessments, as well as the extramuscular assessment, a minimum of 20% improvement is considered clinically meaningful, and for serum levels of muscle associated enzymes, at least 30% improvement is needed to be clinically important. This workshop is the first of several planned to develop multidisciplinary, international consensus on the conduct and reporting of IIM clinical trials.

Adult↗
PubMed2001

The DNA mismatch repair enzyme PMS1 is a myositis-specific autoantigen.

OBJECTIVE: The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue- and event-specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype-specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis. METHODS: We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1-positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases. RESULTS: PMS1, a DNA mismatch repair enzyme, was identified as a myositis-specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP-ribose) polymerase, DNA-dependent protein kinase, and Mi-2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death. CONCLUSION: PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue- and event-specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority.

Adult↗
PubMed1995

Common variable immunodeficiency and inclusion body myositis: a distinct myopathy mediated by natural killer cells.

Inclusion body myositis developed in two men, 36 and 48 years old with long-standing common variable immunodeficiency. Immunophenotypic analysis of the endomysial cells showed an increased number of natural killer (NK) cells (defined as CD57+, CD56+, CD3-, CD8-, CD68-) accounting for 8.5 to 9.5% of the total cells, compared with a mean of 1% in sporadic inclusion body myositis. The remaining cells were CD8+, macrophages, and CD4+ T cells. NK cells were positive for intercellular cell adhesion molecule-1 and invaded muscle fibers negative for major histocompatibility complex (MHC) class I. In contrast to ubiquitous endomysial expression of MHC class I antigen in sporadic inclusion body myositis, the MHC class I in common variable immunodeficiency and inclusion body myositis was absent or weakly expressed in only some of the muscle fibers surrounded by CD8+ cells. Enteroviral or retroviral RNA sequences were not amplified. Treatment with intravenous immunoglobulin improved strength in 1 patient whose repeated muscle biopsy specimen showed normal NK cells. We conclude that inclusion body myositis can develop in patients with common variable immunodeficiency. Common variable immunodeficiency with inclusion body myositis is an immune myopathy mediated by NK cells in a non-MHC class I-restricted cytotoxicity, and by CD8+ cells in an MHC class I-restricted process. This is the first description of an inflammatory myopathy in which NK cells participate in the myocytotoxic process.

Adult↗
PubMed1996

Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a study of 56 patients.

Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-red fibers are common in patients with sporadic inclusion body myositis, and multiple [correction of mutiple] mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.

Adult↗