Epileptic syndrome in systemic lupus erythematosus and neuronal autoantibody associations.

We investigated systemic lupus erythematosus (SLE) patients with epilepsy, a major and organic neurological symptom. Our aim was to test patients for the autoimmune epilepsy-associated antibodies anti-GAD, anti-NMDAR, anti-AMPAR1/2, anti-GABABR and anti-VGKC. We tested sera from ten SLE patients with current or previous episodes of epileptic seizures. In addition, sera were tested for staining on primary hippocampal neurons. The patients' clinical and neuroimaging profile, disease activity and accumulated damage scores and therapeutic regimens administered were recorded, and correlations were evaluated. Patients were negative for all anti-neuronal autoantibodies tested, and showed no staining on primary hippocampal cells, which suggests the absence of autoantibodies against neuronal cell surface antigens. Epileptic seizures were all tonic-clonic, and all patients had high disease activity (mean SLE Damage Acticity Index score 19.3 ± 7.3). Six patients had minor or no brain magnetic resonance imaging findings, and three had major findings. 9/10 patients received immunosuppression for 5 ± 4 months, while anti-convulsive treatment was administered to all patients (4.2 ± 3 years). Our results suggest that the majority of SLE-related epileptic seizures cannot be attributed to the action of a single antibody against neuronal antigens. Studies with larger neuropsychiatric SLE populations and stricter inclusion criteria are necessary to verify these findings.

GAD65 epitope mapping and search for novel autoantibodies in GAD-associated neurological disorders.

Antibodies against Glutamic-acid-decarboxylase (GAD65) are seen in various CNS excitability disorders including stiff-person syndrome, cerebellar ataxia, encephalitis and epilepsy. To explore pathogenicity, we examined whether distinct epitope specificities or other co-existing antibodies may account for each disorder. The epitope recognized by all 27 tested patients, irrespective of clinical phenotype, corresponded to the catalytic core of GAD. No autoantibodies against known GABAergic antigens were found. In a screen for novel specificities using live hippocampal neurons, three epilepsy patients, but no other, were positive. We conclude that no GAD-specific epitope defines any neurological syndrome but other antibody specificities may account for certain phenotypes.

7th International Immunoglobulin Conference: Interlaken Leadership Awards.

The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy.

7th International Immunoglobulin Conference: Interlaken Leadership Awards.

The research presented in this section explores novel applications of immunoglobulin (Ig) therapy in neurological disorders. The results from the upcoming and ongoing trials of Drs Honnorat and Gamez are expected to provide meaningful insights into the treatment of two serious and disabling diseases. The results already being reported from the work of Drs Schmidt and Geis in animal models seem promising, but further proof-of-concept research is warranted to translate their significance to human diseases. Dr Goebel's work in developing animal models of complex regional pain syndrome (CRPS) may provide new insights into predicting which CRPS patients could respond to Ig therapy or other immunotherapies. The work being made possible by a number of the Interlaken Leadership Awards may provide fundamental insights in understanding neurological disorders and improving quality of life for the patients who suffer from them.

Reactivity to AQP4 epitopes in relapsing-remitting multiple sclerosis.

Autoantibodies against the water channel AQP4, expressed predominately in central nervous system astrocytes, are markers and pathogenic factors in Devic's disease. In this study we examined whether Multiple Sclerosis (MS) patients recognize antigenic epitopes on AQP4 that may define distinct disease subsets. We screened sera from 45 patients with relapsing-remitting MS (RRMS) and 13 patients with primary progressive MS (PMS). 23 Neuromyelitis Optica (NMO) patients previously characterized were used as assay positive/negative controls. Sera from 23 patients with Systemic Lupus Erythematosus, 23 with primary Sjogren syndrome without neurological involvement and from 28 healthy individuals were also used as controls. NMO-positive sera exhibited reactivity against the intracellular epitope AQPaa252-275, confirming previous observations. All RRMS sera tested negative for anti-AQP4 antibodies using a cell-based assay, but surprisingly, 13% of them reacted with the epitope AQPaa252-275. PMS, healthy and disease controls showed no specific reactivity. Whether these antibodies define distinct MS subsets and have a pathogenic potential pointing to convergent pathogenetic mechanism with NMO, or are simply markers of astrocytic damage, remains to be determined.

Vigorimeter grip strength in CIDP: a responsive tool that rapidly measures the effect of IVIG--the ICE study.

BACKGROUND AND PURPOSE: In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV-C) intravenously than in those receiving placebo. METHODS: We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP. RESULTS: A randomized double-blind trial was undertaken in 117 CIDP patients who received IGIV-C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut-off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV-C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV-C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV-C group (37.5%-50.9%) than in the placebo group (21.1%-25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1-point deterioration) findings. CONCLUSIONS: Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.

Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and pathogenetic mechanisms.

Sjögren's syndrome is a systemic autoimmune disease that, apart from exocrine glands, may affect every organ or system. Involvement of different sections of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Based on distinct clinical, electrophysiological and histological criteria, the types of neuropathies seen in Sjögren's syndrome include: a) pure sensory which presents with distal symmetric sensory loss due to axonal degeneration of sensory fibers; sensory ataxia due to loss of proprioceptive large fibers (ganglionopathy); or with painful dysethesias (small fiber sensory neuropathy) due to degeneration of cutaneous axons. The latter appears to be the most common neuropathy in Sjögren's syndrome and requires skin biopsy for diagnosis to document loss or reduction of nerve fiber density; b) sensorimotor polyneuropathy affecting sensory and motor axons, often associated with severe systemic or pro-lymhomatous manifestations, such as palpable purpura and cryoglobulinemia, and c) rare types that include autoimmune demyelinating neuropathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. In this review, the frequency, prevalence and diagnostic criteria for each neuropathy subset are discussed and possible pathogenetic mechanisms are outlined.

Fine specificity of antibodies against AQP4: epitope mapping reveals intracellular epitopes.

The autoantibody to aquaporin-4 (AQP4) is a marker and a pathogenetic factor in Neuromyelitis Optica (NMO) (Devic's syndrome). Our aim was to identify B-cell antigenic linear epitopes of the AQP4 protein and investigate similarities with other molecules. To this end, we screened sera from 21 patients positive for anti-AQP4 antibodies (study group), from 23 SLE and 23 pSS patients without neurologic involvement (disease controls) and from 28 healthy individuals (normal controls). Eleven peptides, spanning the entire intracellular and extracellular domains of the AQP4 molecule, were synthesized, and all sera were screened for anti-peptide antibodies by ELISA. Specificity was evaluated by homologous inhibition assays. NMO positive sera exhibited reactivity against 3 different peptides spanning the sequences aa1-22 (AQPpep1) (42.9% of patients), aa88-113 (AQPpep4) (33%) and aa252-275 (AQPpep8) (23.8%). All epitopes were localized in the intracellular domains of AQP4. Homologous inhibition rates were ranging from 71.1% to 84.3%. A 73% sequence homology was observed between AQPpep8' aa257-271, a 15-mer peptide part of the AQPpep8 aa252-275, and the aa219-233 domain of the Tax1-HTLV-1 binding protein (TAX1BP1), a host protein associated with replication of the Human T-Lymphotropic Virus 1 (HTLV-1). Antibodies against the AQP4 and the TAX1BP1 15-mer peptides were detected in 26.3% (N = 5) and 31.6% (N = 6) of NMO positive sera (r(s) = 0.81, P < 0.0001). Healthy controls did not react with these peptides, while homologous and cross-inhibition assays confirmed binding specificity. This first epitope mapping for AQP4 reveals that a significant proportion of anti-AQP4 antibodies target linear epitopes localized in the intracellular domains of the channel. One of the epitopes displays high similarity with a portion of TAX1BP1 protein.

Review: An update on inflammatory and autoimmune myopathies.

The review provides an update on the diagnosis of the main subtypes of inflammatory myopathies including dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). The fundamental aspects on muscle pathology and the unique pathomechanisms of each subset are outlined and the diagnostic dilemmas concerning the distinction of PM from sIBM and NAM are addressed. Dermatomyositis is a complement-mediated microangiopathy leading to destruction of capillaries, hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM, is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmuity with macrophages as the final effector cells causing fibre injury. In PM and sIBM cytotoxic CD8-positive T cells clonally expand in situ and invade major histocompatibility-I-expressing muscle fibres. The pathology of sporadic inclusion body myositis is complex because, in addition to the inflammatory mechanisms, there are degenerative features characterized by vacuolization and the accumulation of stressor and amyloid-related misfolded proteins. Inducible pro-inflammatory molecules, such as interleukin 1-ß, may enhance the accumulation of stressor proteins. The principles for more effective treatment strategies are discussed.

Clinical applications of intravenous immunoglobulins in neurology.

Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.

Toxic and drug-induced myopathies.

Drugs used for therapeutic interventions either alone or in combination may sometimes cause unexpected toxicity to the muscles, resulting in a varying degree of symptomatology, from mild discomfort and inconvenience to permanent damage and disability. The clinician should suspect a toxic myopathy when a patient without a pre-existing muscle disease develops myalgia, fatigue, weakness or myoglobinuria, temporally connected to the administration of a drug or exposure to a myotoxic substance. This review provides an update on the drugs with well-documented myocytoxicity and cautions the clinicians to be alert for the potential toxicity of newly marketed drugs; highlights the clinical features and pathomechanisms of the induced muscle disease; and offers guidance on how best to treat and distinguish toxic myopathies from other acquired or hereditary muscle disorders. Practical issues regarding the diagnosis and management of statin-induced myopathies are emphasized. Myotoxicity resulting from direct insertion of transgenes to the muscle, an exciting new tool currently tested for treatment of muscular dystrophies, is also discussed.

Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of alphaB-crystallin is associated with amyloid precursor protein and accumulation of beta-amyloid.

BACKGROUND: In the pathology of sporadic inclusion body myositis (sIBM), the relevance of cell stress molecules such as the heat shock protein alphaB-crystallin, particularly in healthy appearing muscle fibres, has remained elusive. METHODS: 10 muscle biopsies from sIBM patients were serially stained for haematoxylin-eosin, trichrome and multi-immunohistochemistry for neural cell adhesion molecule (NCAM), alphaB-crystallin, amyloid precursor protein (APP), desmin, major histocompatibility complex I, beta-amyloid and ubiquitin. Corresponding areas of all biopsies were quantitatively analysed for all markers. Primary myotube cultures were exposed to the proinflammatory cytokines interleukin (IL)-1beta and interferon (IFN)-gamma. RESULTS: In human myotubes exposed to IL-1beta+IFN-gamma, overexpression of APP was accompanied by upregulation of alphaB-crystallin. In sIBM muscle biopsies, over 20% of all fibres displayed accumulation of beta-amyloid or vacuoles/inclusions. A clearly larger fraction of the fibres were positive for alphaB-crystallin or APP. In contrast with the accumulation of beta-amyloid in atrophic fibres, a major part of fibres positive for APP or alphaB-crystallin showed no morphological abnormalities. Expression of APP and alphaB-crystallin significantly correlated with each other and most double positive fibres displayed accumulation of beta-amyloid, vacuoles or an atrophic morphology. In almost all of these fibres, other markers of degeneration/regeneration such as NCAM and desmin were evident as additional indicators of a cell stress response. Some fibres double positive for APP and alphaB-crystallin displayed infiltration by inflammatory cells. CONCLUSION: Our results suggest that alphaB-crystallin is associated with overexpression of APP in sIBM muscle and that upregulation of alphaB-crystallin precedes accumulation of beta-amyloid. The data help to better understand early pathological changes and underscore the fact that a network of cell stress, inflammation and degeneration is relevant to sIBM.

Health-related quality-of-life improvements in CIDP with immune globulin IV 10%: the ICE Study.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy trials have demonstrated the efficacy of IV immunoglobulin vs placebo. However, these trails have not addressed the long-term impact on health-related quality of life (HRQoL). METHODS: One hundred seventeen patients in a randomized, double-blind, response-conditional crossover trial received immune globulin IV, 10% caprylate/chromatography purified (IGIV-C [Gamunex(R)]), or placebo every 3 weeks for up to 24 weeks in the first period (FP). Participants whose inflammatory neuropathy cause and treatment disability score did not improve by >/=1 point received alternate treatment in a 24-week crossover period (CP). In either period, participants who improved and completed treatment were eligible to be randomly reassigned to a blinded 24-week extension phase (EP). HRQoL analyses were conducted using the Short Form-36(R) (SF-36) and the Rotterdam Handicap Scale (RHS). RESULTS: In the FP, greater improvements in both SF-36 physical and mental component scores were observed with IGIV-C vs placebo, with a significant improvement in the physical component score (difference 4.4 points; 95% confidence interval [CI] 0.7-8.0). Improvements in all SF-36 domains favored IGIV-C vs placebo, with physical functioning, role-physical, social functioning, and mental health reaching significance. Participants receiving IGIV-C experienced a larger improvement in RHS vs those receiving placebo (difference 3.4 points; 95% CI 1.4-5.5; p = 0.001). In the CP, similar general trends were observed. In the EP, mean SF-36 improvements were generally improved or maintained in participants who continued IGIV-C therapy; however, worsening was observed in participants re-randomized to placebo. CONCLUSIONS: Long-term therapy with immune globulin IV, 10% caprylate/chromatography purified, improves and maintains health-related quality of life in chronic inflammatory demyelinating polyradiculoneuropathy.

[Targeting B cells in multiple sclerosis. Current concepts and strategies]. / B-Zell-gerichtete Multiple-Sklerose-Therapie. Aktueller Stand.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease of the CNS and a leading cause of lasting neurological disability in younger adults. In the last decade our knowledge of its immunopathogenesis expanded vastly. It is now widely appreciated that B cells are key players in the autoreactive immune network. They exert far more functions than merely being the precursors of antibody-producing plasma cells. B cells act as efficient antigen-presenting cells and may stimulate an autoreactive immune response through secretion of proinflammatory cytokines. It is thus only logical to test therapeutic strategies targeting B cells in MS. Rituximab is a depleting chimeric monoclonal antibody directed against CD20 and expressed on developing, naïve, and memory B cells but not stem or plasma cells. Several smaller studies have been conducted that led to a placebo controlled, double blind phase II study on efficacy which was reported recently. The results are very promising, meeting not only the primary endpoint of reduction of the surrogate MRI marker of contrast-enhancing lesions but also showing a reduction in clinical relapse rate of patients treated with rituximab. This review discusses the role of autoreactive B cells in the context of MS, analyzes the B-cell-depleting treatment studies reported, and provides information on planned and future B-cell-directed therapeutic strategies in MS.

Induction of experimental ataxic sensory neuronopathy in cats by immunization with purified SGPG.

IgM paraproteins in about 50% of the patients with neuropathy associated with IgM gammopathy react with carbohydrate moieties in myelin-associated glycoprotein (MAG) and in sulfated glucuronic glycolipids (SGGLs) in human peripheral nerves. However, the role of anti-MAG/SGGL antibodies in the pathogenesis of neuropathy remains unclear. In order to induce an animal model of neuropathy associated with anti-MAG/SGGL antibodies, cats were immunized with sulfoglucuronyl paragloboside (SGPG). All four cats immunized with SGPG developed clinical signs of sensory neuronopathy within 11 months after initial immunization, characterized by unsteadiness, falling, hind limb weakness and ataxia. In two cats the ataxia and hind limb paralysis were so severe that the animals had to be euthanized. Pathological examination revealed sensory ganglionitis with inflammatory infiltrates in the dorsal root ganglia. No overt signs of pathology were noted in the examined roots or nerves. High titer anti-SGPG/MAG antibodies were detected in all 4 cats immunized with SGPG but not in 3 control cats. Our data demonstrate that immunization of cats with SGPG induced anti-SGPG antibodies and sensory neuronopathy clinically resembling the sensory ataxia of patients with monoclonal IgM anti-MAG/SGPG antibodies. This study suggests that these anti-MAG/SGPG antibodies play a role in the pathogenesis of this neuropathy.

T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis.

BACKGROUND: Sporadic IBM (sIBM) is characterized by invasion of non-necrotic MHC-I class-expressing muscle fibers by clonally expanded CD8+ cells. Whether the endomysial cells expand in situ or are recruited from the circulation is unclear. METHODS: We used CDR3 spectratyping of the T cell receptor (TCR) V beta chains to determine clonal expansion of T cells in simultaneously obtained muscle and peripheral blood lymphocytes (PBL) from 12 patients with sIBM, and compared the difference between the two compartments. To determine whether the identified clones belonged to autoinvasive T cells, we performed immunohistochemistry on the same muscle specimens. Spectratyping was repeated in four muscle biopsies 1 year after the first. RESULTS: In control PBL, all 24 TCR V beta subfamilies had a polyclonal or Gaussian distribution. In sIBM PBL, 5% of the V beta subfamilies demonstrated a single and 16% up to three peaks. In contrast, in their corresponding muscles, 27% (p = 0.0003) of the V beta subfamilies demonstrated a single and 71% (p < 0.0001) up to three peaks. Among the amplified subfamilies, V beta 9, 10, 11, 16, 18, 23, and 24 showed the highest degree of restriction within muscle. Immunohistochemistry demonstrated that the clonally expanded CD8+ cells were autoinvasive. In follow-up biopsies the clonality persisted with an unchanged degree of restriction, but not always of the same subfamilies, suggesting epitope spreading. CONCLUSION: In sporadic inclusion body myositis, the endomysial T cells are specifically recruited to the muscle or expand in situ. The restriction of multiple V beta subfamilies and their change over time suggests recognition of various local antigens and epitope spreading.

Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial.

OBJECTIVE: To determine if modafinil can improve fatigue in patients with post-polio syndrome. METHODS: We used a randomized, placebo-controlled crossover trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale as the main outcome measure. Other measures included the Visual Analog Scale for Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality of life) was assessed using the 36-Item Short-Form. Analysis of variance for repeated measures was applied to assess treatment, period, and carryover effects. RESULTS: Thirty-six patients were randomized, 33 of whom (mean age: 61 years) completed required interventions. Treatment with modafinil was safe and well-tolerated. After adjusting for periods and order effects, no difference was observed between treatments. CONCLUSION: Based on the utilized measures of outcome modafinil was not superior to placebo in alleviating fatigue or improving quality of life in the studied post-polio syndrome population.

Update on idiopathic inflammatory myopathies.

The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies.

Skin involvement and outcome measures in systemic autoimmune diseases.

This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sjögren syndrome (SS), dermatomyositis (DM) and Behçet syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis.

Autoimmune muscular pathologies.

The T cell-mediated mechanism responsible for Polymyositis and inclusion Body Myositis and the complement-mediated microangiopathy associated with Dermatomyositis are reviewed. The management of autoimmune myopathies with the presently available immunotherapeutic agents as well as new therapies and ongoing trials are discussed.