Auto-Immunity Highlights最新文献

IgG4-related disease (IgG4-RD) is relatively a new growing entity of immune-mediated origin, characterized by a mass-forming lesion, the infiltration of IgG4-positive plasma cells and occasionally elevated serum IgG4. It is considered to be both a systemic inflammation and sclerosing disease. The most common manifestations are parotid and lacrimal swelling, lymphadenopathy and autoimmune pancreatitis. Sclerosing cholangitis and retroperitoneal fibrosis are among the other mentioned frequent manifestations. The diagnosis should be approved histo-pathologically but other conditions such as lymphoma should be carefully excluded. Patients with IgG4-RD respond beneficially to glucocorticoid therapy especially when given at early onset stages. In some cases, the combination of immunosuppressive agents is required.

Over the past two decades, we have witnessed an extraordinary change in autoimmune diagnostics, characterized by the progressive evolution of analytical technologies, the availability of new tests, and the explosive growth of molecular biology and proteomics. Aside from these huge improvements, organizational changes have also occurred which brought about a more modern vision of the autoimmune laboratory. The introduction of automation (for harmonization of testing, reduction of human error, reduction of handling steps, increase of productivity, decrease of turnaround time, improvement of safety), consolidation (combining different analytical technologies or strategies on one instrument or on one group of connected instruments) and integration (linking analytical instruments or group of instruments with pre- and post-analytical devices) opened a new era in immunodiagnostics. In this article, we review the most important changes that have occurred in autoimmune diagnostics and present some models related to the introduction of automation in the autoimmunology laboratory, such as automated indirect immunofluorescence and changes in the two-step strategy for detection of autoantibodies; automated monoplex immunoassays and reduction of turnaround time; and automated multiplex immunoassays for autoantibody profiling.

Purpose: Recent studies have demonstrated that serum/plasma DNA and RNA molecules in addition to proteins can serve as biomarkers. Elevated levels of these nucleic acids have been found not only in acute, but also in chronic conditions, including autoimmune diseases. The aim of this study was to assess cell-free DNA (cfDNA) levels in sera of rheumatoid arthritis (RA) patients compared to controls.

Methods: cfDNA was extracted from sera of patients with early and established RA, relapsing-remitting multiple sclerosis patients (RRMS) and healthy subjects, and its concentration was determined by quantitative PCR using two amplicons, Alu115 and β-actin205, corresponding to Alu repetitive elements and the β-actin single-copy gene, respectively. Serum DNase activity was measured by a single radial enzyme diffusion method.

Results: Reduced levels of cfDNA were observed in patients with established RA in comparison with healthy controls, early RA patients and RRMS patients. There were no significant differences in cfDNA concentration between healthy controls, early RA and RRMS patients. Total DNase activity appeared to be similar in the sera of all tested groups.

Conclusions: Our results demonstrate that cfDNA levels are strongly reduced in the sera of established RA patients, which is not caused by changes in DNase activity. Measurement of cfDNA can distinguish established RA patients from early RA patients. Thus, cfDNA may serve as a biomarker in RA.

Idiopathic inflammatory myopathies (IIM) are a rare disease; so far standardized therapy has not been adequately defined by national or international guidelines or recommendations. Corticosteroids are the mainstay of treatment, but these drugs are burdened by several side effects. Thus, additional treatment based on immunosuppressive agents, especially azathioprine, methotrexate, mycophenolate mofetil and cyclosporine, is often needed. This combinate approach both improves the disease response and allows reduction of the dosage of corticosteroids, decreasing the risk of steroid-related long-term complications. Biological agents, particularly B cell depleting agent, are emergent therapeutic tools for refractory cases. Notably, drugs currently used for the therapy of IIM or other rheumatologic and non-rheumatologic conditions can induce myopathy. Drug-induced myopathies represent a considerable part of the complex topic of muscular disorders and should be always considered in the usual diagnostic work-up of a subject with muscle disease. Several mechanisms have been advocated to explain muscular damage induced by a number of drugs and, although a recovery after drug removal is usually observed, severe or persistent myopathy may be observed following the administration of some drugs, particularly in subjects with genetic predisposition. In this review the traditional and novel therapeutic approaches for patients with IIM, particularly biologics, will be discussed and an overview on drug-induced myopathies will also be provided.

An association between many psychiatric and gluten-related disorders has been known for some time. In the case of schizophrenia and mood disorders, the major psychiatric disorders, there is much evidence, not without contradictions, of a possible association between schizophrenia and celiac disease. The association between mood disorders and gluten-related disorders, especially celiac disease, has only been studied for depression, often coupled with anxiety, and very recently for bipolar disorder. Since non-celiac gluten sensitivity is now known to be different from celiac disease, many studies have shown that gluten sensitivity is also associated with major psychiatric disorders. Here we review the literature on the association between schizophrenia/mood disorders and celiac disease/gluten sensitivity, pointing out the differences between these associations.

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by inflammation of the skeletal muscle. Weakness, mainly affecting the proximal muscles, is the cardinal muscular symptom in IIM. In patients with dermatomyositis, peculiar skin lesions are observed. The assessment of patients with IIM includes clinical and laboratory evaluation, and clinimetric measurements. Different tools have been proposed to measure muscular and extramuscular disease activity and damage in patients with IIM. A core set of measurements to use in clinical practice was recently proposed. Among laboratory features the increase of serum creatine kinase (CK) is considered a hallmark of muscle inflammation/damage. However, subjects with persistent CK elevation, without any evidence of a definite myopathy, are often seen in clinical practice and need a careful assessment. Indeed, CK blood levels can also increase in non-myopathic conditions, e.g. in case of intense physical exercise, assumption of some drugs (statins), muscular dystrophy, muscular trauma or in case of neuro-muscular disorders which all should be considered in the diagnostic work-up. The assessment of patients with IIM and hyperCKemia will be discussed in this paper.

The gold standard to characterize idiopathic inflammatory myopathies is the morphological, immunohistochemical and immunopathological analysis of muscle biopsy. Mononuclear cell infiltrates and muscle fiber necrosis are commonly shared histopathological features. Inflammatory cells that surround, invade and destroy healthy muscle fibers expressing MHC class I antigen are the typical pathological finding of polymyositis. Perifascicular atrophy and microangiopathy strongly support a diagnosis of dermatomyositis. Randomly distributed necrotic muscle fibers without mononuclear cell infiltrates represent the histopathological hallmark of immune-mediated necrotizing myopathy; meanwhile, endomysial inflammation and muscle fiber degeneration are the two main pathological features in sporadic inclusion body myositis. A correct differential diagnosis requires immunopathological analysis of the muscle biopsy and has important clinical implications for therapeutic approach. In particular, unnecessary, potentially harmful, immune-suppressive therapy should be avoided alike in dystrophic myopathies with secondary inflammation.

Autoantibodies are powerful diagnostic tools in idiopathic inflammatory myopathies, especially for confirming the diagnosis and contributing to the definition of disease subsets. They are present in over 80 % of patients with immuno-mediated myositis and directed towards ubiquitously expressed intracellular complexes. Most of these autoantibodies are reported also in other autoimmune diseases, while some are considered myositis-specific. Myositis autoantibodies are traditionally categorized in two groups, based on their diagnostic accuracy: myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA), the latter mostly occurring in myositis-overlap syndromes. Besides the so-called traditional MSA, including anti-synthetases, anti-SRP and anti-Mi-2 antibodies, additional newly conceived immune targets have been recently identified, mostly in patients with severe forms of dermatomyositis or necrotizing myopathy. They mainly encompass enzymatic proteins essentially involved in the regulation of gene transcription or post-translational modifications, i.e., TIF1-γ, NXP-2, MDA5, SAE and HMGCR. Among the MAA, anti-PM/Scl and anti-Ku characterize an overlap polydermatomyositis/systemic sclerosis syndrome with severe interstitial lung involvement.

Systemic lupus erythematosus (SLE) is considered an autoimmune disease with multiorgan involvement. Many advances have been made during the last decade regarding inflammatory pathways, genetic and epigenetic alterations, adaptive and innate immune system mechanisms specifically involved in SLE pathogenesis. Apoptosis has been proposed as an important player in SLE pathogenesis more than a decade ago. However, only recently new key apoptotic pathways have been investigated and the link between apoptotic debris containing autoantigens, innate immunity and ongoing inflammation has been further elucidated. Better understanding of cellular mechanisms and involved cytokines contributed to the development of new biological drugs specifically addressed for SLE therapy.

Purpose: To evaluate the impact of the introduction of the anti-phosphatidylserine/prothrombin autoantibodies (aPS/PT) in the laboratory diagnostic process of anti-phospholipid antibody syndrome (APS).

Methods: Four hundred and twenty-one patients (71.5 % females; 53 ± 15 years) presenting a medical prescription for aPS/PT antibodies were consecutively enrolled in the study from March 2013 to August 2013. During the same period, aPS/PT were additionally investigated in a selected series of 62 patients characterized by difficult lupus anticoagulant (LA) tests interpretation and in a retrospective series of 52 LA positive cases with available data about anti-prothrombin (aPT) antibodies. The aPS/PT antibodies, as well as the anti-cardiolipin (aCL), the anti-β2 glycoprotein I (aβ2GPI) and the aPT antibodies were analyzed by ELISA. LA was tested according to the recommended criteria, performing both the screen and the confirm steps.

Results: Overall, aPS/PT IgM positive (>30 U/ml) and/or IgG frankly positive (>40 U/ml) antibodies were found in 49/421 (11.6 %) cases. Among the LA positive patients, we found 56.1 % aPS/PT positive versus 31.7 % aCL and/or aβ2GPI positive cases, with limited (17.1 %) simultaneous positivity. The PS/PT complex resulted the newly recognized specificity in about 27 % of patients recruited from the subset with difficult LA test interpretation. Compared to aPT antibodies, the aPS/PT antibodies displayed a much higher sensitivity (55.8 versus 15.4 %) in LA positive patients.

Conclusions: The introduction of aPS/PT antibodies in the diagnostic process of APS is highly recommended, since they disclose a notable diagnostic performance and a high correlation with LA activity, such that they can be a viable alternative.