An Italian Multicenter Study on Anti-NXP2 Antibodies: Clinical and Serological Associations.

The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p < 0.0001). As for clinical features, NXP2+ more frequently develop specific skin manifestations and less frequently features related with overlap myositis and anti-synthetase syndrome. IP confirmed NXP2 positivity in 31 of 52 available sera (62%). Most clinical associations were confirmed comparing NXP2 LB+/IP+ versus NXP2-negative myositis, with the following exceptions: inclusion-body myositis diagnosis was not detected, whilst dysphagia and myositis were found more frequently in NXP2 LB+/IP+ patients. The 21 LB+ /IP-myositis patients did not show differences in clinical features when compared with the NXP2-myositis patients and more frequently displayed multiple positivity at LB. Risk of developing cancer-associated myositis was similar between NXP2-positive and NXP2-negative myositis patients, either when detected by LB or IP. Protein-IP confirmed NXP2 antibodies in nearly 60% of sera positive for the same specificity with commercial assay. Double-positive cases rarely occurred in myositis patients with a clinical diagnosis other than dermatomyositis. Patients only positive by LB (LB+/IP-) did not display clinical features typical of NXP2. NXP2 positivity by LB should be confirmed by other methods in order to correctly diagnose and characterize patients affected by idiopathic inflammatory myositis.

Diagnostics of myasthenic syndromes: detection of anti-AChR and anti-MuSK antibodies.

This paper presents the Italian guidelines for autoantibody testing in myasthenia gravis that have been developed following a consensus process built on questionnaire-based surveys, internet contacts and discussions during dedicated workshops of the sponsoring Italian Association of Neuroimmunology (AINI). Essential clinical information on myasthenic syndromes, indications and limits of antibody testing, instructions for result interpretation and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Association between "sarcoidosis-like" disease and common variable immunodeficiency (CVI): a new CVI variant showing an activation of the immune system.

BACKGROUND: Particular interest has been recently addressed to the association between a Granulomatous Sarcoidosis-like Disease (GSa-LD) and Common Variable Immunodeficiency (CVI). METHODS: The present paper discusses the clinical and immunopathological findings of the association between CVI and GSa-LD, based on four patients, whose clinical course was followed for about seven years. The lung involvement was studied by high resolution chest computed tomography scansion, classical parameters of lung function and diffusion lung carbon monoxide. All patients underwent bronchoalveolar lavage in order to exclude tuberculosis infection by culture analysis and polymerase chain reaction as well as to investigate the presence of active alveolitis. RESULTS: The clinical progression of patients were consistent with that reported in the literature confirming some distinct features in comparison with patients with CVI. In particular, patients with CVI/GSa-LD exhibited a reduced rate of respiratory infectious diseases, despite low levels of circulating immunoglobulins, and displayed a lower ability to develop bronchiectasies. Accordingly, the absolute number of circulating CD8+DR+, but not of CD4+DR+ T cells in CVI-GSa-LD patients were significantly lower than in the group of patients suffering from CVI alone. Moreover, patients with CVI/GSa-LD did not develop lung fibrosis (at least for the period of our follow-up) even though they show an active lymphocytic alveolitis in the bronchoalveolar lavage and displayed an higher degree of monocyte-macrophage activation. CONCLUSIONS: A better definition of the molecular and cellular mechanisms involved in the development of systemic macrophage and T cell activation in immunodeficiency patients is required, in order to clarify the pathogenesis of sarcoidosis-like disease in CVI.