Group Of Autoimmune Diseases Research Articles

Etiologies of Acute Optic Neuritis in Thailand: An Observational Study of 171 Patients.

PurposeTo analyze the demographic patterns, clinical characteristics and etiologies of acute optic neuritis (ON).MethodsThis retrospective observational study included patients with acute ON who presented to a university hospital in Bangkok, Thailand, between January 2010 and March 2020. The demographic details, clinical characteristics and etiologies of acute ON were evaluated.ResultsA total of 171 patients were included in the study (78.4% [n=134] female; mean age 45 years [standard deviation 15.4 years]; 32.2% [n=55] bilateral involvement). The most common type of acute ON was idiopathic (51.5%), followed by neuromyelitis optica spectrum disorder (NMOSD, 30.9%), other autoimmune disorders (9.9%), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD, 5.3%), multiple sclerosis (MS, 1.8%), and postinfection (0.6%). In the other autoimmune disorders group, 2 patients developed systemic lupus erythematosus (1.2%), 2 Sjogren’s syndrome (1.2%), 1 RA (0.6%), 1 anti-NMDAR (0.6%), 3 anti-Jo1 (1.8%), 2 c-ANCA (1.2%), 1 anti-centromere (0.6%), and 5 nonspecific autoimmune disorders (2.9%). In the idiopathic group, 38.6% developed single isolated ON, 1.8% relapsing isolated ON and 11.1% chronic relapsing inflammatory optic neuropathy.ConclusionThe most common form of acute ON in this study, similar to other Asian countries, was idiopathic. Idiopathic-ON shared some phenotypes with NMOSD and MOGAD. We also reported patients with anti-NMDAR, anti-Jo1, c-ANCA and anti-centromere disorders. Improvements in antibody detection have widened the range of possible etiologies of acute ON. The study highlighted the important role of antibodies in creating effective treatments in the future.

Assessment of the usefulness of macroenzyme determination in the situation of increased plasma enzyme activity in the absence of clinical symptoms

Introduction: The increased activity of serum enzymes is usually a reason of multiple, often expensive and invasive diagnostic procedures. However, there are situations in which abnormal enzyme activity persists for many months or years, and detailed studies do not confirm the existence of anatomic disease. Such is the case when enzymes form complexes with immunoglobulins on the basis of the immune antigen-antibody reaction. This phenomenon is usually benign condition, is transient and does not require treatment. Aim of study: Detection of the macroenzymes in patients with elevated serum enzyme activity. Evaluation of the relationship between the presence of macroenzymes and the age of patients, body mass index, lipid profile, chronic and autoimmune diseases. Material and methods: Macroenzymes were examined by polyethylene glycol precipitation (PEG) in 121 patients with elevated values of liver or pancreatic enzymes. Results: In the study group, a statistically significant difference was found comparing the BMI of men and women. BMI was significantly higher in men with macroenzymes (p = 0.006). It was shown that the BMI of people with serum macroenzymes is significantly higher (p = 0.049) than those without macroenzymes. A statistically significant correlation was observed between the presence of macroamylase and body weight, r = 0.33, p = 0.039. A positive correlation of triglycerides and macrogenzofacts in the serum was found. Macroamylase was observed the most frequently in the healthy group and those suffering from chronic diseases (45.83% and 42.86%). In the group of autoimmune diseases (autos) the most common was macro-GGTP (42.86%). In patients with inflammatory bowel disease, 80% of the confirmed macroenzymes in serum were macro-CK.

“Multiple sclerosis plus”: Does it influence the disease course?

AbstractObjectivesTo study the association between multiple sclerosis (MS) and other autoimmune diseases (AID).MethodsFrom a cohort of 635 patients with MS, 66 patients with an history of AID were selected. Controls, matched 1:1, were chosen from the population of patients with MS without autoimmune comorbidities. Further analysis aimed to compare these groups.ResultsThe prevalence of comorbid AID in our population was 10.4%. The mean age was 43 ± 13 years; 77% were women. A total of 15 different types of AID were identified, the predominant one was autoimmune thyroiditis (18/66; 27%). In 46% of patients, the AID was diagnosed before, and in 49%, it was diagnosed after the diagnosis of MS. The presence of family history of AID was not associated with the risk of developing AID. Our analysis found no association between the presence of AID and disease activity (new lesions, gadolinium enhancement, mean of annual relapse rate, initiation of a second‐line treatment), either when considering each variable individually or within a composite score. The median Extended Disability Status Scale and Multiple Sclerosis Severity Score was 1.5 (interquartile range [IQR] 3.0) and 1.0 (IQR 3.0), respectively, in the AID group, and 1.5 (IQR 3.0) and 2.0 (IQR 3.0), respectively, in the control group, and the difference was not statistically significant. The presence of a concomitant AID influenced therapeutic choice in nine patients.ConclusionsThe present study underlines the varied range of AID that might coexist with MS. This common ground does not seem to have a negative effect on the disease course.

High Risk of Sudden Sensorineural Hearing Loss in Several Autoimmune Diseases according to a Population-Based National Sample Cohort Study

Objective: We investigated the risk of sudden sensorineural hearing loss (SSNHL) in patients with autoimmune diseases compared with a control group in a population-based study using a National Health Insurance Service National Sample Cohort data from Korea. Methods:We enrolled autoimmune-disease patients who were ≥20 years of age in 2006 into the autoimmune-disease group, and selected a control group with similar demographic characteristics. We tracked the 2 groups from 2006 to 2015 and compared the proportions of patients who developed SSNHL. Results: Of 13,250 patients in the autoimmune-disease group, 145 experienced an SSNHL event (1.09%). Of the 66,250 in the control group, 484 experienced an SSNHL event (0.73%). The SSNHL risk was significantly higher in the autoimmune-disease group than in the control group. SSNHL incidence was significantly higher among patients with antiphospholipid syndrome (APS), multiple sclerosis (MS), rheumatoid arthritis (RA), and connective-tissue diseases including Sjögren syndrome and Behçet disease. In detailed stratified analyses using reinforced additional diagnostic codes, only RA patients had a significantly higher SSNHL incidence than the control group. Conclusion: The association of several autoimmune diseases with SSNHL was evaluated in this large-scale, population-based, big-data study. The risk of SSNHL was significantly higher in patients with APS, MS, RA, and connective-tissue diseases including Sjögren syndrome and Behçet disease than in patients without autoimmune diseases. SSNHL, in particular, was significantly associated with RA according to detailed analyses using reinforced additional diagnostic codes.

Autoimmune disease in patients with diffuse large B-cell lymphoma: occurrence and impact on outcome

Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well as the impact of AID on outcome has not been extensively studied. The main purpose of this study was to establish the occurrence of AIDs in a population-based cohort of DLBCL patients and to compare outcomes in patients with or without AID treated with rituximab(R)-CHOP/CHOP-like treatment. We also aimed to analyse gender differences and the potential role of different AIDs on outcome and the frequency of treatment-associated neutropenic fever.Patients and methods: All adult patients treated 2000–2013 with R-CHOP/CHOP-like treatment for DLBCL in four counties of Sweden were included (n = 612). Lymphoma characteristics, outcome and the presence of AID were obtained through medical records.Results: The number of patients with AID was 106 (17.3%). Thyroid disease dominated (n = 33, 31.1%) followed by rheumatoid arthritis (RA) (n = 24, 22.6%). The proportion of AID was significantly higher in females (59/254, 23.2%) vs. in males (47/358, 13.1%) (p = .001). In the whole cohort there was no difference in event free survival (EFS) or overall survival (OS) between patients with or without AID. However, patients with an AID primarily mediated by B-cell responses (thyroid disorders excluded) had a worse OS (p = .037), which seemed to affect only women. The AID group more often had neutropenic fever after first treatment (16.0% vs 8.7%, p = .034) and those with neutropenic fever had a worse OS (p = .026) in Kaplan-Meier analyses.Conclusion: There is a high prevalence of AID among patients with DLBCL. AIDs categorized as primarily B-cell mediated (in this study mainly RA, systemic lupus erythematosus and Sjögren’s syndrome) may be associated with inferior OS. AID patients may be more prone to neutropenic fever compared to patients without concomitant AID.

Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

110 Background: Anecdotal and early evidence suggest ICIs are being used in patients with advanced malignancies and history of AD, despite such patients being typically excluded from traditional clinical trials. We compared the outcomes of patients with or without AD, all of whom had ICI treatment for aNSCLC. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in ASCO’s CancerLinQ. Patients with Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 visits from Jan 2011 to Nov 2018 were included. AD status prior to ICI treatment was identified using ICD-9/ICD-10 codes or AD medications (including steroids). Symphony claims data were linked via tokenization to build cohorts. Time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS) and overall survival (OS) were compared across the two cohorts using the log-rank test. Cox Proportional Hazards Model was used to adjust for covariates. Adverse events (AEs) were compared using Chi-Square and Fisher’s Exact Test. Active AD was defined as evidence of autoimmune disease in the year prior to starting ICIs. Results: Among 2425 patients with aNSCLC treated with ICIs, AD was present in 22% (N=538). Median OS in all patients was 12.4 months (95% CI 11.3-13.5). TTD, TTNT, rwPFS and OS did not differ between the two cohorts (Table). There was no association between AD status and outcomes. There was no increased incidence of AEs in the AD group; however a sub-analysis among patients with active AD showed higher rates of select AEs including endocrine, GI and blood disorders. Conclusions: This analysis demonstrates that patients with evidence of AD prior to receiving ICI have similar outcomes compared to patients with no evidence of AD. Further research is needed to better understand the impact of active AD on the risk of AEs and patient outcomes. [Table: see text]

Relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e' was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e' (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e', and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions: Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.

Etiology of Liver Disease and Cardiovascular Abnormalities in Patients on a Liver Transplantation Waiting List.

BackgroundThe classical cardiovascular risk factors and changes in the circulatory system secondary to end-stage liver disease (ESLD) are associated with an increased risk of cardiac abnormalities (CAs) in patients waiting for liver transplantation (LTx).The aim of this study was to assess the relationship between the etiology of liver disease and the presence of CAs in patients qualified for LTx.Material/MethodsThe study enrolled patients qualified to LTx due to ESLD at the Clinical Hospital of the Medical University of Warsaw between 2013 and 2016. Out of 396 patients: 65, 157, 117, and 57 had ESLD due to the alcoholic liver disease (ALD), viral infections (VIR), autoimmune disorders (AUTO), and different etiologies (OTHER), respectively.ResultsAn increased frequency of hypertension and diabetes mellitus were observed in ALD and VIR groups, while for hyperlipidemia, the highest rates were observed in ALD and AUTO groups. Significant differences in CAs rates were observed for resting tachycardia, prolonged QT interval, bradycardia, and left ventricular diastolic dysfunction. After adjustment for age, MELD, and Child-Pugh scores, hyperlipidemia (26% vs. 7–15%, p<0.048) was most frequently observed in the AUTO group, while poor aerobic capacity (49% vs. 21–34%, p<0.009) dominated in the OTHER group.ConclusionsThe frequency of hyperlipidemia, and poor aerobic capacity were directly related to the etiology of liver disease, while the remaining associations resulted from effects of age, MELD, and Child-Pugh score.

Macrophage depletion reduces disease pathology in factor H dependent immune complex glomerulonephritis

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of autoimmune disorders that predominantly affects small vessels. The onset of the disease is closely associated with ANCA. Renal involvement, also known as ANCA-associated glomerulonephritis (AGN), is one of the most common manifestations of AAV. In this mini-review, we described the clinical and pathological features of AGN. We then focused on recent studies on the mechanism of acute kidney lesions, including fibrinoid necrosis and crescent formation. Following the basic aspects of kidney injury in AGN, we demonstrated the clinical importance of kidney injury in determining the outcome of patients with AGN. The prognostic value of the 2010 Histopathological Classification of AGN and validating studies were summarized. Finally, treatment and novel therapeutic strategies were introduced addressing the importance of optimizing management of this patient population.

Antineutrophil cytoplasmic antibodies-associated glomerulonephritis: From bench to bedside

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of autoimmune disorders that predominantly affects small vessels. The onset of the disease is closely associated with ANCA. Renal involvement, also known as ANCA-associated glomerulonephritis (AGN), is one of the most common manifestations of AAV. In this mini-review, we described the clinical and pathological features of AGN. We then focused on recent studies on the mechanism of acute kidney lesions, including fibrinoid necrosis and crescent formation. Following the basic aspects of kidney injury in AGN, we demonstrated the clinical importance of kidney injury in determining the outcome of patients with AGN. The prognostic value of the 2010 Histopathological Classification of AGN and validating studies were summarized. Finally, treatment and novel therapeutic strategies were introduced addressing the importance of optimizing management of this patient population.

Genetic differences between type 1 diabetes with and without other autoimmune diseases.

Clusters of autoimmune diseases (ADs) are present in some people with type 1 diabetes. This clustering suggests the existence of common genetic backgrounds for abnormal autoimmunity in these individuals. However, the genetic differences between type 1 diabetes patients with and without other ADs are not well known. To investigate the clinical background and genetic differences between type 1 diabetes patients with and without other ADs, single nucleotide polymorphisms (SNPs) in the CTLA4, SUMO4, PTPN22, IRF5, STAT4, and BLK genes were analysed by using either a TaqMan assay or direct sequencing. The frequencies of alleles, genotypes of each gene, and the human leukocyte antigen (HLA) haplotype were analysed to investigate differences among 3 groups: type 1 diabetes with systemic ADs (group A), type 1 diabetes with other organ-specific ADs (group B), and type 1 diabetes without other ADs (group C). The frequency of the C allele in the -1123G>C SNP in the PTPN22 gene promoter was significantly higher in groups A and B than in group C (P=.0258 and .0207, respectively). The allele frequencies of the other SNPs were comparable. The frequency of HLA DRB1*0405-DQB1*0401 was significantly higher in groups A and B than in group C (P=.021 and .0395, respectively). The -1123G>C SNP in the PTPN22 gene promoter and HLA DRB1*0405-DQB1*0401 might influence the concurrence of systemic and organ-specific ADs in patients with type 1 diabetes.

Clinical features and drug selection in 54 patients with inflammatory bowel disease and comorbid autoimmune disease

Objective To explore the differences in disease location, pathological feature, disease severity, extraintestinal manifestations and drug treatment between inflammatory bowel disease (IBD) patients with comorbid autoimmune disease (AD) and simple IBD patients. Methods From January 2009 to December 2014, the clinical data of 54 IBD patients with comorbid AD and at the same period 74 simple hospitalized IBD patients were retrospectively analyzed. According to IBD type and whether combined with AD, patients were divided into Crohn′s disease (CD)+ AD group (n=16), CD group (n=26), ulcerative colitis (UC)+ AD group (n=38) and UC group (n=48). Chi square test was performed to compare the differences in disease severity, location, extraintestinal manifestations and drug treatment between IBD patients with and without AD. Results There was no statistically significant difference in location among four groups (all P>0.05). The most common concomitant AD of IBD was rheumatoid arthritis (20.4%, 11/54) and ankylosing spondylitis (13.0%, 7/54). The proportion of mild active patients of CD+ AD group was lower than that of CD group (2/16 vs 53.8% (14/26), χ2=7.180, P=0.007), while the proportion of severe active patients was significantly higher that of CD group (6/16 vs 0, χ2=8.519, P=0.004). There was no statistically significant difference in moderate active patients between the two groups (P=0.808). Main type of patients of UC+ AD group (76.3%, 29/38) and UC group (68.8%, 33/48) were moderate active patients. There was no statistically significant difference in disease stage and location (all P>0.05). The incidence of extraintestinal manifestations of IBD+ AD group (55.6%, 30/54) was significantly higher than that of IBD group (9.5%, 7/74, χ2=32.279, P<0.01), and the main manifestation was arthritis (37.0%(20/54) vs 5.4%(4/74), χ2=20.504, P<0.01). The rate of glucocorticoid and immunosuppressant application in IBD+ AD group was higher than that of IBD group (40.7%(22/54) vs 17.6%(13/74), χ2=8.438, P=0.004; 20.4%(11/54) vs 0, χ2=14.000, P<0.01). Conclusions The condition of patients with IBD and comorbid AD is more severe, and the incidence of extraintestinal manifestations is higher. Early treated with glucocorticoid and immunosuppressant could effectively achieve remission. Key words: Inflammatory bowel diseases; Autoimmune diseases; Extraintestinal manifestations; Glucocorticoids; Immunosuppressive agents

Neurosurgical Approaches in Demyelinating Disorders; Where are We Now?

Demyelinating diseases of the central nervous system (CNS) are a group of autoimmune disorders affecting the myelin sheets of CNS neurons resulting in different neurological deficits and disability. Multiple sclerosis (MS), Devic’s disease, progressive multifocal leukoencephalopathy, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO) are among the most common types of demyelinating disorders. Currently MS is the leading cause of neurological disability in young population after trauma . The incidence and prevalence of MS is increasing worldwide primarily due to increase the incidence in female population. Globally, the median estimated incidence of MS is 5.2 (range: 0.5-20.6) per 100,000 p-yrs, the median estimated prevalence of MS is 112.0 (with a range of 5.2-335) per 100,000 p-yrs, and the average disease duration is 20.2 years (range: 7.6-36.2). In Iran, the prevalence and incidence of MS is estimated to be 54.51 and 5.87 per 100,000. Diagnosis of demyelinating disorders is a controversial issue and several criteria has been introduced for the aforementioned subject. Diagnostic criteria for clinically definite MS require documentation of two or more episodes of symptoms and two or more signs that reflect pathology in anatomically noncontiguous white matter tracts of the CNS. The second may be documented by abnormal paraclinical tests such as MRI or evoked potentials (EPs).&#x0D; The standard treatment for patients with demyelinating disorders and especially MS is the medical management. Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis have shown efficacy of new oral disease-modifying drugs, teriflunomide and dimethyl fumarate, with similar or better efficacy than the injectable disease-modifying drugs, IFN-β and glatiramer acetate. In addition, the new oral drugs seem to have a favorable safety profile. Further, the monoclonal antibody alemtuzumab, which in clinical trials has shown superiority to subcutaneous IFN-β 1a, has been approved in Europe. In acute exacerbation and flare up of the disease, methylprednisolone pulse is the only approved treatment.&#x0D; Although the standard of treatment of MS and other demyelinating disorders is medical, but neurosurgical procedures especially the functional neurosurgical interventions has found their way in management of patients with demyelinating disorders. These interventions are used to treat the complications of MS and demyelinating disorders such as tremor, trigeminal neuralgia, movement disorders and neuropathic pains. Most of these interventions are stereotactic in order to obtain precise targeting of a special deep brain nucleus. The first application of deep brain stimulation (DBS) in patients with MS was for treatment of tremor. Recently it has been demonstrated that DBS of ventral intermediate (VIM) nucleus of thalamus results in alleviation of severe, disabling tremor in patients with MS. Other experiments have also demonstrated decreased tremor and improved quality of life in MS patients responsive to DBS.&#x0D; Neuropathic pain and trigeminal neuralgia are among the other complications of demyelinating disorders which are associated with disability and decreased quality of life. Several investigations have shown that DBS of thalamic nuclei would be effective in treatment of neuropathic pain in patients with MS, although the results are controversial and need further investigations. The trigeminal neuralgia is often treated by microsurgical decompression of the trigeminal nerve. However this approach is not effective in patients with demyelinating disorders as they have different pathology. Case series have shown that Gamma Knife surgery (GKS) is an effective and safe treatment for trigeminal neuralgia in patients with MS. No clinical trial is available for comparing the results and outcome between GKS and microsurgical approach. However results of case series are favorable.&#x0D; There are still other field that could be approached surgically in patients with demyelinating disorders. Recent bodies of evidence have demonstrated a link between cervical cord plaques and discopathy in those with MS which needs further investigation. Tumefactive demyelinating lesions (TDL) are another issues observed in patients with MS which have unknown course and pathology. The link between demyelinating disorders and brain tumors is also another issues which deserves further investigation. To take a long story short, although the role of functional neurosurgical procedures in management of patients with demyelinating disorders especially MS is still limited, but there is optimistic horizons for growing role of neurosurgical procedures in management of different complications of demyelinating disorders refractory to medical therapy.Â

The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study.

Autoimmune disease (AD) is common in patients with Wiskott-Aldrich syndrome (WAS) and patients with WAS who has an AD usually constitute a high-risk group with poor outcome. However, knowledge of AD in WAS is limited in China. In this study, medical records of 53 patients with WAS at Children´s Hospital of Chongqing Medical University from April 2004 to January 2014 were evaluated retrospectively and 14 patients (26%) had at least one AD. Autoimmune hemolytic anemia (AIHA) was the most common and detected in 12 patients (23%), other complications included immune thrombocytopenia (n = 1), immune neutropenia (n = 1), autoimmune arthritis (n = 1), and renal injury (n = 1). No significant differences were found in the level of serum immunoglobulins and lymphocyte subsets between the AD group and non-AD group. Although eight patients with AD received hematopoietic stem cell transplantation (HSCT), three patients died of pulmonary infection after HSCT. AD is frequent in Chinese patients with WAS and AIHA was the most common. AD is a poor prognosis factor for WAS and should be treated as early as possible by HSCT. • Autoimmune disease is common in patients with WAS. • Manifestations, follow-up finding, and treatment approaches of autoimmune disease in Chinese patients with WAS have received less attention in the literature. What is New: • This study is firstly intended for evaluation of the clinical and immune characteristics of autoimmune disease in a large series Chinese patients with WAS. • AD is frequent in Chinese patients with WAS and AIHA is the most common.

Clinical significance of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern in autoimmune disease

Objective To explore the prevalence of the nuclear dense fine speckled (DFS) immunofluorescence pattern in routine antinuclear antibodies (ANA) testing and its significance in patients with autoimmune diseases (AID). Methods The ANA in 13 728 specimens were measured by indirect immunofluorescence (IIF) using HEp–2 cell slides from department of clinical laboratory, wenling hospital from 2011 to 2014. The frequencies, clinical manifestations and laboratory features of DFS positivity were restrospectively analyzed in patients with AID, using χ2 test. Results ANA was positive in 20.56%(2 822/13 728) of the total patients, and the frequency of DFS pattern was observed in 1.81%(248/13 728) of the total patients and in 8.79%(248/2 822) of the patients with ANA positivity. In different age groups (≤20 years old, 21–49 years old and ≥50 years old), there were statistical significance of DFS pattern positive rate (male: χ2=18.17, P<0.01; female: χ2=1 500.00, P<0.01). And the highest frequency of ANA positivity was observed in patients from department of rheumatology (30.07%). The frequency of DFS pattern was higher in the departments of infection (32.58%), dermatology (21.76%), neurology (18.58%) and nephrology (6.73%) among the patients with ANA positivity (χ2=123.00, P<0.01). Amony the 248 cases with DFS pattern positivity.41 cases were AID (16.53%) and 207 cases were non– autoimmune diseases (83.47%). In AID group 13 cases were autoimmune thyroiditis (31.71%), 12 cases were rheumatoid arthritis (29.27%), 4 cases were autoimmune liver disease (9.76%), 4 cases were undifferentiated connective tissue disease (9.76%), 3 cases were ankylosing spondylitis (7.32%), 2 cases were Sjogren's disease (4.88%), 2 cases were inflammatory bowel disease (4.88%) and 1 case was systemic lupus erythematosus (2.44%). The titers of DFS in patients with AID were predominantly above 1∶320 and less than 1∶100 in non–AID. AID patients with DFS pattern positivity have different clinical manifestations and laboratory features. Howerer, antinuclear antibodies (ANAs) in 15 specific auto–antibodies were all negative. Conclusions The DFS pattern is a common pattern in ANA positivity patients and it mainly exists in non–AID patients. Further more, it is suggested that patients with DFS pattern identified by IIF should then be tested for anti–DFS70 antibodies with a specific immunoassay. (Chin J Lab Med, 2015, 38: 173–177) Key words: Autoimmune disease; Antibodies, antinuclear; Fluorescent antibody technique, indirect

Required role of apoptotic myogenic precursors and toll-like receptor stimulation for the establishment of autoimmune myositis in experimental murine models.

Muscle regeneration is a hallmark of the idiopathic inflammatory myopathies (IIMs), a group of autoimmune disorders that are characterized by leukocyte infiltration and dysfunction of the skeletal muscle. Despite detailed studies describing the clinical and histopathologic features of IIMs, the immunopathogenesis of these disorders remains undefined. The aim of this study was to investigate the immunopathologic processes of autoimmune myositis in experimental murine models. Expression of the autoantigen histidyl-transfer RNA synthetase (HisRS) was analyzed in mice with acutely injured or dystrophic muscles, in inflammatory leukocytes, and in purified satellite cells. Anti-HisRS antibodies and myositis induction were assessed in mice after muscle injury and immunization with apoptotic satellite cells or C2C12 myoblasts, in the presence or absence of the Toll-like receptor 7 (TLR-7) agonist R848. Muscle necrosis, leukocyte infiltration, and myofiber regeneration induced by toxic agents (cardiotoxin or glycerol) or promoted by genetic disruption of the α-sarcoglycan/dystrophin complex in mice were uniformly associated with up-regulated expression of HisRS. Although regenerating myofibers and purified satellite cells are known to show increased expression of HisRS in these settings, anti-HisRS antibodies were not detectable. However, intramuscular immunization with ultraviolet B-irradiated, HisRS-expressing apoptotic myoblasts in the presence of R848 triggered the production of anti-HisRS IgG antibodies as well as persistent lymphocyte infiltration and prolonged/delayed muscle regeneration. Conversely, intramuscular administration of R848 alone or in combination with living or postapoptotic/necrotic myoblasts failed to generate this myositis phenotype. In the presence of TLR/adjuvant signals and underlying muscle injury, apoptotic myogenic precursors expressing high levels of autoantigen can provoke autoantibody formation and lymphocytic infiltration of muscle tissue, effectively replicating the features of IIM.

The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1∗15 (OR = 2.17) and HLA-DRB1∗03 (OR = 1.81) alleles with MS, HLA-DRB1∗03 with SLE (OR = 2.49), HLA-DRB1∗01 (OR = 1.79) and HLA-DRB1∗04 (OR = 2.81) with RA, HLA-DRB1∗07 with Ps + PsA (OR = 1.79), HLA-DRB1∗01 (OR = 2.28) and HLA-DRB1∗08 (OR = 3.01) with SSc, and HLA-DRB1∗03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1∗13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1∗13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1∗13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1∗13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

AB0718 Autoimmune sarcopenia in patients with rheumatoid arthritis and systemic lupus erythematosus

BackgroundSarcopenia refers to age-related loss of muscle mass and function. However, autoimmune sarcopenia refers to excessive weight loss usually with disproportionate muscle wasting due to cytokine excess. Previous studies have...

Recomendaciones sobre el uso de belimumab en el lupus eritematoso sistémico. Guía de Práctica Clínica GEAS-SEMI

Biological therapies are based on the administration of various types of synthetic molecules related to the immune response. Their use has spread in recent years to the field of systemic autoimmune diseases, particularly to systemic lupus erythematosus (SLE). Until 2011, these diseases were not included in the therapeutic indications approved by international regulatory agencies. Therefore, the use of biological therapies was restricted to clinical trials and to compassionate use for cases refractory to standard treatments (off-label use), which require the approval of the Health Ministry. In 2011, belimumab, a human monoclonal antibody that specifically binds to the soluble form of the protein human B lymphocyte stimulator BlyS, was approved for use in patients with SLE. Because the clinical information on the use of this new drug in patients with SLE has only been obtained from the results of randomized trials, the Study Group of Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine (SEMI) has developed therapeutic guidelines. These guidelines are based on the current scientific evidence on the use of belimumab in SLE patients in the clinical practice.

Complement in antineutrophil cytoplasmic antibody-associated vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of autoimmune disorders. It was previously assumed that the complement system is not involved in the development of ANCA-associated vasculitis due to its "pauci-immune" feature in renal histology. However, increasing evidence indicates that activation of the complement system, especially via the alternative complement pathway, plays a crucial role in the pathogenesis of ANCA-associated vasculitis. In this brief review, we discuss the evidence, including invivo, invitro, and clinical studies, for complement system activation in ANCA-associated vasculitis.