Explore the vast range of titles available.

Introduction/ObjectivesA line blot (LB) assay is a multi-analyte platform capable of simultaneously detecting multiple anti-nuclear antibody specificities. Here, we evaluated the performance of a commercial LB assay developed for the identification of myositis- or systemic sclerosis (SSc)-related autoantibodies (autoAbs).MethodWe screened 300 serum samples from patients with various connective tissue diseases using an LB assay and compared the results of myositis- or SSc-related autoAbs with those identified by RNA and protein immunoprecipitation (IP) assays or indirect immunofluorescence (IIF).ResultsThe IP assays revealed anti-Jo-1 Abs in 14 patients, anti-EJ Abs in 12, anti-PL-7 Abs in 8, anti-PL-12 Abs in 4, anti-Mi-2 Abs in 6, anti-SRP Abs in 8, anti-topoisomerase I Abs in 54, anti-RNA polymerase III Abs in 24, anti-U3 RNP Abs in 9, anti-Th/To Abs in 9, anti-Ku Abs in 14 and anti-hUBF Abs in 4, whereas IIF identified anti-centromere in 35. Good agreement between the IP assays and the LB assay was found only for anti-Jo-1 and anti-centromere antibodies. When a cut-off was adjusted to reconcile with the results of IP assays, the detection performance of LB assay was improved for anti-EJ, anti-PL-7, anti-PL-12, anti-SRP, anti-topoisomerase I and anti-RNA polymerase III Abs. However, the results of anti-Mi-2, anti-U3 RNP, anti-Th/To, anti-hUBF and anti-Ku Abs remained discordant between the LB assay and IP assays at all cut-off levels.ConclusionsDetection of myositis- or SSc-related autoAbs using a commercial LB assay requires great caution since it can yield analytically false-positive or false-negative results.Key Points• A line blot (LB) assay is a multi-analyte platform capable of simultaneously detecting multiple antibodies with anti-nuclear specificities.• Detection of myositis- or systemic sclerosis-related autoantibodies using a commercial LB assay requires great caution since it can yield analytically false-positive or false-negative results.

Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies. Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients' serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated. In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006). Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM.

Interstitial lung disease (ILD) has been recognized as a frequent manifestation associated with a substantial morbidity and mortality burden in patients with autoimmune rheumatic disorders. Serum autoantibodies are considered good biomarkers for identifying several subsets or specific phenotypes of ILD involvement in these patients. This review features the role of several autoantibodies as a diagnostic and prognostic biomarker linked to the presence ILD and specific ILD phenotypes in autoimmune rheumatic disorders. The case of the diverse antisynthetase antibodies in the antisynthease syndrome or the anti-melanoma differentiation-associated 5 protein (MDA5) antibodies as a marker of a severe condition such as rapidly progressive ILD in patients with clinically amyopathic dermatomyositis are some of the associations herein reported in the group of myositis spectrum disorders. Specific autoantibodies such as the well-known anti-topoisomerase I (anti-Scl70) or the anti-Th/To, anti-U11/U12 ribonucleoprotein, and anti-eukaryotic initiation factor 2B (eIF2B) antibodies seems to be specifically linked to ILD in patients with systemic sclerosis. Overlap syndromes between systemic sclerosis and myositis, also have good ILD biomarkers, which are the anti-PM/Scl and anti-Ku autoantibodies. Lastly, other not so often reported disorders as being associated with ILD but recently most recognized as is the case of rheumatoid arthritis associated ILD or entities herein included in the miscellaneous disorders section, which include anti-neutrophil cytoplasmic antibody-associated interstitial lung disease, Sjögren’s syndrome or the mixed connective tissue disease, are also discussed.

Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Diagnosis of ITP is still challenging because ITP has been diagnosed by exclusion. Exclusion of thrombocytopenia due to bone marrow failure is especially important in Japan because of high prevalence of aplastic anemia compared to Western countries. Hence, we propose a new diagnostic criteria involving the measurement of plasma thrombopoietin (TPO) levels and percentage of immature platelet fraction (RP% or IPF%); 1) isolated thrombocytopenia with no morphological evidence of dysplasia in any blood cell type in a blood smear, 2) normal or slightly increased plasma TPO level (< cutoff), 3) elevated RP% or IPF% (> upper limit of normal), and 4) absence of other conditions that potentially cause thrombocytopenia including secondary ITP. A diagnosis of ITP is made if conditions 1-4 are all met. Cases in which criterion 2 or 3 is not met or unavailable are defined as “possible ITP,” and diagnosis of ITP can be made mainly by typical clinical course. These new criteria enable us to clearly differentiate ITP from aplastic anemia and other forms of hypoplastic thrombocytopenia and can be highly useful in clinical practice for avoiding unnecessary bone marrow examination as well as for appropriate selection of treatments.

Summary What is this summary about? Systemic sclerosis (SSc) is a condition that affects the immune system (the body’s natural defence system) and causes the skin to harden and thicken in large patches. Research shows that 30% to 90% of people with SSc also have interstitial lung disease (ILD), a condition that causes inflammation and scarring of the lungs. When people have SSc and ILD, it is known as SSc-associated ILD or SSc-ILD. The authors of this plain language summary of publication (PLS-P) reviewed different articles to find out what the key issues were in the way doctors and patients with SSc-ILD communicate with each other. What were the results? The key messages from the studies were: Most patients felt uneasy when they were diagnosed with SSc-ILD Good communication between doctors and patients at the first visit is crucial as it sets the tone for future relationships Both doctors and patients avoid talking about how SSc-ILD symptoms may get worse (prognosis) or the subject of death. Patients should be encouraged to ask questions to address important and personal topics that would not be talked about otherwise Patients may feel intimidated by a doctor, which could interfere with communication Doctors must be able to listen and show empathy to build a relationship with patients and be aware that different communication styles may suit a patient during different stages in their journey Doctors should avoid using a lot of technical terms. Patients felt metaphors helped them understand their condition better Patients have different awareness, thoughts, and feelings about SSc-ILD than doctors. If doctors understand this, it may improve the communication between doctors and patients Ways to close the gap between the way doctors and patients communicate include patients having the opportunity to access: Self-learning and patient organizations Peer-mentoring (patients mentoring other patients) Information technology Shared decision-making, where the doctor and patient work together to come to a decision about treatment and care What do the results mean? The best way to improve the feelings patients have when they are diagnosed with SSc, including SSc-ILD, is to improve the quality of the communication between doctors and patients. The quality of the first meeting between a doctor and patient sets the tone for future checkups, especially if the doctor can listen, show empathy, and allow the patient to ask questions. Improving the patient’s knowledge about SSc-ILD, for example by using websites, reading printed materials, or taking part in peer-mentoring schemes, may also contribute to a better conversation.

Patients with interstitial lung disease associated with systemic sclerosis were treated with usual care plus placebo or nintedanib. The annual rate of change in forced vital capacity assessed over a 52-week period was −52.4 ml per year with nintedanib and −93.3 ml per year with placebo. There were no differences in other measures of systemic sclerosis.

ContextThe very early diagnosis of systemic sclerosis (VEDOSS) criteria were developed to diagnose systemic sclerosis (SSc) at a very early stage. However, several studies have applied these criteria inconsistently, often using them to identify patients at a predisease stage. This use has created confusion between the concept of VEDOSS and pre-SSc. With growing interest in predisease states in autoimmunity, a consensus definition of pre-SSc is mandatory.ObjectiveAs a preliminary step towards such definition, this scoping review aimed to map existing definitions of pre-SSc and VEDOSS in the literature, identify item combinations used and capture conceptual variations.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines, PubMed and Web of Science were searched using the terms ‘VEDOSS’ OR ‘very early diagnosis of systemic sclerosis’ OR ‘pre-scleroderma’ OR ‘pre-systemic sclerosis’ OR ‘pre-SSc’.ResultsOf 106 records screened, 40 full texts were included (eight on pre-SSc and 32 on VEDOSS). Most articles (80%) originated from Europe. Three distinct definitions of pre-SSc were identified, alongside 13 different applications of VEDOSS criteria. Although 62.5% of studies cited the 2011 VEDOSS consensus, only 31.3% applied the complete definition incorporating the three step 1 essential items and step 2 confirmation tools.ConclusionThis scoping review highlights the variability of the definitions of VEDOSS and pre-SSc that have been used in the literature. The absence of a consensus definition for pre-SSc contributes to overlapping and blurring boundaries between these concepts. A consensus effort is warranted to select a core set of items for a standardised definition of pre-SSc.

The epidemiology of primary immune thrombocytopenia (ITP) is not well-characterized in the general population. Most published studies, which have included relatively small numbers of ITP patients, have been conducted in England or Scandinavian countries. No epidemiologic data from Asian countries have been published. This study describes the epidemiology of ITP in a Japanese population. We analyzed the database registry of the Ministry of Health, Labour, and Welfare of Japan, and extracted newly diagnosed acute and chronic ITP patients with a platelet count of <100 × 10 9 /L. From 2004 to 2007, 7,774 cases of ITP were reported, giving an overall incidence of 2.16/100,000/year. The incidence differed greatly between males and females, being 1.72 and 2.58, respectively. The median age of the total affected population was 56 years old. In male patients, there was a striking preponderance of boys below 4 years and a very high peak among those aged 75–89 years. In female patients, the number of ITP patients appeared to show a trimodal distribution by age, with the first peak representing patients below 4 years, the second peak those aged 20–34 years, and the third peak those aged 50–89 years. In conclusion, the incidence of ITP in Japan is not markedly different from that of European countries studied to date. This population-based study reveals that, contrary to previously published studies, the maximum age-specific incidence is in the eighth decade.