Diagnosis and classification of idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively termed myositis, sharing symptoms of muscle weakness, fatigue and inflammation. Other organs are frequently involved, supporting the notion that these are systemic inflammatory diseases. The IIMs can be subgrouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis-specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the antisynthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease and anti-SRP and anti-HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as interstitial lung disease. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude noninflammatory myopathies. Treatment effect and prognosis vary by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical. The lack of such criteria was the main rationale for the development of new classification criteria for IIMs, which are summarized in this review; the historical background regarding previous diagnostic and classification criteria is also reviewed. As the IIMs are rare diseases with a prevalence of 10 in 100 000 individuals, an international collaboration was essential, as was the interdisciplinary effort including experts in adult and paediatric rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1500 patients from 47 centres worldwide and are based on clinically easily available variables.

Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies.

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.

Immunoglobulin A and CD8 T-cell mucosal immune defenses protect against intranasal infection with Chlamydia pneumoniae.

Chlamydia pneumoniae initiates infection in humans via the mucosal epithelia of the respiratory tract; therefore, immunity at this mucosal site is believed to be important to control infection with this pathogen. We compared the protective capacity of immunization in mice with two C. pneumoniae antigens, namely the major outer membrane protein (MOMP) and the heat shock protein 60 (HSP-60), against intranasal (i.n.) infection with the bacteria when given as protein or DNA and when administered by i.n. or intraperitoneal (i.p.) routes. Our data showed that i.n. immunizations with both antigens delivered as DNA were protective against C. pneumoniae infection, probably due to induction of cell-mediated immune responses. Our study also revealed that i.n. immunizations with MOMP, but not with HSP-60, given as protein induced protective local immune responses in the respiratory tract against C. pneumoniae infection. Moreover, no protection was induced by either antigen when the i.p. route of immunization was used. We further investigated in immunoglobulin (Ig)A-deficient mice whether the reduction in the bacterial loads observed when MOMP was administered intranasally was related to the strong local IgA responses induced by this route of immunization. Our data showed that IgA-deficient mice were more susceptible to infection than wild-type mice, suggesting that the induction of local IgA responses may play a role in the protection of the respiratory tract against C. pneumoniae infections.