Autoimmune Diagnosis Research Articles

The neurologic significance of celiac disease biomarkers.

To report neurologic phenotypes and their etiologies determined among 68 patients with either (1) celiac disease (CD) or (2) no CD, but gliadin antibody positivity (2002-2012). Neurologic patients included both those with the CD-prerequisite major histocompatibility complex class II human leukocyte antigen (HLA)-DQ2/DQ8 haplotype, and those without. The 3 groups were as follows: group 1 (n = 44), CD or transglutaminase (Tg)-2/deamidated gliadin immunoglobulin (Ig)A/IgG detected; group 2 (n = 15), HLA-DQ2/DQ8 noncarriers, and gliadin IgA/IgG detected; and group 3 (n = 9), HLA-DQ2/DQ8 carriers, and gliadin IgA/IgG detected. Neurologic patients and 21 nonneurologic CD patients were evaluated for neural and Tg6 antibodies. In group 1, 42 of 44 patients had CD. Neurologic phenotypes (cerebellar ataxia, 13; neuropathy, 11; dementia, 8; myeloneuropathy, 5; other, 7) and causes (autoimmune, 9; deficiencies of vitamin E, folate, or copper, 6; genetic, 6; toxic or metabolic, 4; unknown, 19) were diverse. In groups 2 and 3, 21 of 24 patients had cerebellar ataxia; none had CD. Causes of neurologic disorders in groups 2 and 3 were diverse (autoimmune, 4; degenerative, 4; toxic, 3; nutritional deficiency, 1; other, 2; unknown, 10). One or more neural-reactive autoantibodies were detected in 10 of 68 patients, all with autoimmune neurologic diagnoses (glutamic acid decarboxylase 65 IgG, 4; voltage-gated potassium channel complex IgG, 3; others, 5). Tg6-IgA/IgG was detected in 7 of 68 patients (cerebellar ataxia, 3; myelopathy, 2; ataxia and parkinsonism, 1; neuropathy, 1); the 2 patients with myelopathy had neurologic disorders explained by malabsorption of copper, vitamin E, and folate rather than by neurologic autoimmunity. Our data support causes alternative to gluten exposure for neurologic dysfunction among most gliadin antibody-positive patients without CD. Nutritional deficiency and coexisting autoimmunity may cause neurologic dysfunction in CD.

Development of SLE among "potential SLE" patients seen in consultation: long-term follow-up.

To identify factors associated with development of systemic lupus erythematosus (SLE) among patients evaluated at a tertiary care Lupus Center for potential SLE. We identified patients first seen at the Brigham and Women's Hospital Lupus Center between 1 January 1992 and 31 December 2012 and thought to have potential SLE by a board-certified rheumatologist. All had 1-3 SLE ACR criteria at initial visit and > 2 follow-up visits ≥ 3 months apart. We reviewed medical records through 15 May 2013 for: SLE signs and symptoms, autoimmune serologies, prescriptions and diagnoses by board-certified rheumatologists. Bivariable analyses and multivariable logistic regression models were used to identify independent predictors of developing SLE. Two hundred and sixty four patients met inclusion criteria. At initial visit, mean age was 39.2 (SD 12.4) years, 94% were female and 67% white. Mean number of SLE ACR criteria was 2.7 (SD 1.0) and 88% were antinuclear antibody (ANA) positive at initial consultation. Mean follow-up time was 6.3 (SD 4.3) years and 67% were prescribed hydroxychloroquine in follow-up. At most recent visit, 56 (21%) had been diagnosed with SLE; 47 (18%) were thought not to have SLE and 161 (61%) were still considered to have potential SLE. In multivariable regression models, oral ulcers (OR 2.40, 95% CI 1.03-5.58), anti-dsDNA (OR 2.59, 95% CI 1.25-5.35) and baseline proteinuria or cellular casts (OR 16.20, 95% CI 1.63-161.02) were independent predictors of developing SLE. The most common other final diagnoses included fibromyalgia, Sjögren's syndrome, mixed connective tissue disease and cutaneous lupus. Among patients with potential SLE at initial consultation, 21% were diagnosed with definite SLE within 6.3 years. Oral ulcers, anti-dsDNA and proteinuria or cellular casts were independent predictors of developing definite SLE. A better means of accurately identifying those who will develop SLE among those presenting with potential disease is necessary.

Increased Post-Operative Stiffness after Arthroscopic Suprapectoral Biceps Tenodesis

Objectives:Biceps tenodesis can be performed open or arthroscopically and can be positioned in a suprapectoral or subpectoral position. Suprapectoral tenodesis can be carried out arthroscopically, whereas the subpectoral tenodesis is performed as an open procedure. The goal of this study is to compare the incidence of postoperative stiffness between arthroscopic suprapectoral and open subpectoral biceps tenodesis and evaluate risk factors for its occurrence.Methods:Study Design: The charts of all patients who underwent arthroscopic or open biceps tenodesis who were a minimum of two years post-procedure were reviewed. Patients with preoperative frozen shoulder, prior shoulder surgery, or massive rotator cuff tears which required longer post-operative immobilization were excluded. Post-operative stiffness was defined as persistent range of motion deficit (<100oof forward flexion and abduction; <40o of internal or external rotation) and pain resulting in a diagnosis of post-operative frozen shoulder and requiring either an injection, lysis of adhesions/manipulation, or both.Analysis:Means were calculated for continuous variables and compared using Students t test. Frequencies for categorical variables were compared using chi square tests.Results:We identified 249 consecutive biceps tenodeses from 2008-11 (106 arthroscopic, 143 open) that met inclusion and exclusion criteria. A significantly increased incidence of post-operative stiffness was found in the arthroscopic tenodesis cohort as compared to the open cohort (17.9% vs. 5.6%, p=0.002). The groups were otherwise well matched. (Table I). Further analysis was performed comparing patients with and without post-operative stiffness within the arthroscopic cohort. (Table II) Female gender (63.2% vs 33.3%, p = 0.016) and smoking (36.8% vs 16.1%, p = 0.040) were independent risk factors for post-operative stiffness after arthroscopic tenodesis. Location of the tenodesis from the top of the humeral head as measured on x-ray was 32.4 mm (stiff cohort) versus 50.3 mm (non-stiff cohort) (p < 0.0001). BMI, workmans compensation status and concomitant procedures did not significantly increase the risk of post-operative stiffness. Auto-immune diagnoses such as diabetes mellitus and thyroid disease were also not significant predictors for post-operative stiffness. Of the 19 arthroscopic tenodesis patients who developed post-operative stiffness, 18 had normal range of motion and were pain free by final follow up. In 16 patients, symptoms resolved with one or more injections; two patients did require reoperation, undergoing arthroscopic lysis of adhesions and manipulation.Conclusion:Our results demonstrate a notable incidence of post-operative stiffness after arthroscopic suprapectoral tenodesis. This occurs more commonly in females and smokers. A more proximal location of the tenodesis is noted in patients who develop post-operative stiffness. The relationship between this issue and the arthroscopic suprapectoral tenodesis technique may be multifactorial, with potential etiologies including increased soft-tissue manipulation, fluid extravasation, bursal resection in the sub-deltoid space, increased risk of bleeding in the region of the bicipital sheath, or possibly an effect related to over-tensioning of the biceps with a presentation mimicking post-operative capsulitis, that improves over time and with symptom-based management.

Diagnosis and classification of drug-induced autoimmunity (DIA)

Since sulfadiazine associated lupus-like symptoms were first described in 1945, certain drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified by systemic lupus erythematosus (SLE). Among the drugs, procainamide and hydralazine are considered to be associated with the highest risk for developing lupus, while quinidine has a moderate risk, and all other drugs have low or very low risk. More recently, drug-induced lupus has been associated with the use of newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors and cytokines. In addition to lupus, other major autoimmune diseases, including vasculitis and arthritis, have also been associated with drugs. Because resolution of symptoms generally occurs after cessation of the offending drugs, early diagnosis is crucial for treatment strategy and improvement of prognosis. Unfortunately, it is difficult to establish standardized criteria for DIA diagnosis. Diagnosis of DIA requires identification of a temporal relationship between drug administration and the onset of symptoms, but the relative risk with respect to dose and duration for each drug has rarely been determined. DIA is affected by multiple genetic and environmental factors, leading to difficulties in establishing a list of global clinical features that are characteristic of most or all DIA patients. Moreover, the distinction between authentic DIA and unmasking of a latent autoimmune disease also poses challenges. In this review, we summarize the highly variable clinical features and laboratory findings of DIA, with an emphasis on the diagnostic criteria.

Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report

IntroductionMyasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism.Case presentationWe report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine.ConclusionsMany patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter.Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist.

The targeting of β‐cells by T lymphocytes in human type 1 diabetes: clinical perspectives

This review focuses on genes that control β-cell targeting in autoimmune, type 1-dependent, diabetes (T1D) and on insulin as the major autoantigen recognized by T lymphocytes throughout the disease process. T1D associates with multiple gene variants. Beyond genes that predispose to general failure of immune tolerance to self, loci identified by the analysis of crosses between non-obese diabetic (NOD) and conventional mouse strains harbour genes that control β-cell targeting or the deviation of autoimmunity towards other tissues. We report here the role of genes encoding co-activation molecules involved in the activation of T lymphocytes, ICOS and ICOS ligand (B7RP1). NOD mice which are deficient in either of these two molecules are protected from diabetes, but instead develop a neuromuscular autoimmune disease. We also report the characterization in humans of T lymphocytes that are specific for major β-cell autoantigens, especially insulin. This opens the way towards new bioassays in the diagnosis of autoimmunity and towards autoantigen-specific immunotherapy in T1D. In order to develop a new preclinical model of T1D that would allow testing insulin epitopes to induce immune tolerance in vivo, we developed a mouse that is deficient in endogenous major histocompatibility complex class I and class II genes and deficient for the two murine insulin genes and that express human class I, class II and insulin genes.

Autoimmune, Atopic, and Mental Health Comorbid Conditions Associated With Alopecia Areata in the United States

To evaluate the prevalence of comorbid conditions among patients with alopecia areata (AA) seen at tertiary care hospitals in Boston, Massachusetts, during an 11-year period. Retrospective cross-sectional study. Tertiary care hospitals in Boston, including Brigham and Women's Hospital and Massachusetts General Hospital. We identified 3568 individuals with AA seen in the Partners health care system in Boston between January 1, 2000, and January 1, 2011. We performed comprehensive searches of the Research Patient Data Repository using International Classification of Diseases, Ninth Revision code 704.01. We randomly selected 350 patients and manually reviewed their medical records to train and validate a novel artificial intelligence program. This program then used natural language processing to review free-text medical records and confirm a diagnosis of AA. To confirm the algorithm, we manually reviewed a subset of records and found 93.9% validity. The prevalence of comorbid conditions was assessed. Common comorbid conditions included autoimmune diagnoses (thyroid disease in 14.6%, diabetes mellitus in 11.1%, inflammatory bowel disease in (2.0%) [corrected], systemic lupus erythematosus in 4.3%, rheumatoid arthritis in 3.9%, and psoriasis and psoriatic arthritis in (6.3%) [corrected], atopy (allergic rhinitis, asthma, and/or eczema in 38.2% and contact dermatitis and other eczema in 35.9%), and mental health problems (depression or anxiety in 25.5%). We also found high prevalences of hyperlipidemia (24.5%), hypertension (21.9%), and gastroesophageal reflux disease (17.3%). This profile was different from that seen in a comparison psoriasis and psoriatic arthritis group. We found a high prevalence of comorbid conditions among individuals with AA presenting to academic medical centers in Boston. Physicians caring for patients with AA should consider screening for comorbid conditions.

AB0730 Kikuchi-fujimoto disease: Past and future dangerous liaisons

BackgroundKikuchi-Fujimoto disease (KFD) is known as histiocytic necrotizing lymphadenitis. The most important signs and symptoms are cervical lymph node enlargement and fever. This disease is usually benign and self-limiting. The...

Striational antibodies in a paraneoplastic context

The clinical significance of striational antibodies (StrAbs) detected in the course of paraneoplastic antibody testing is unknown. We compared all 203 striational antibody (StrAb)-seropositive patients identified (2004-2005) during evaluation for paraneoplastic antibodies with age- and sex-matched seronegative controls. Thymoma and myasthenia gravis (MG) were significantly more common among cases (P<0.0001). Cancers more rarely detected after StrAb detection were adenocarcinoma in 5 patients and sarcoma in 3 patients. All patients who had a cancer identified after StrAb testing had a titer of ≥ 1:7680 or a coexisting muscle AChR-binding antibody. Autoimmune disorders more commonly observed among cases (with any StrAb value) included: hypothyroidism; rheumatoid arthritis; and pernicious anemia (all P<0.05). StrAbs may serve as a diagnostic clue for an autoimmune diagnosis. There is a low likelihood of oncological significance in patients with StrAb titers <1:7680 without coexisting paraneoplastic Abs.

The human microbiome and autoimmunity

To demonstrate how dysbiosis of the human microbiome can drive autoimmune disease. Humans are superorganisms. The human body harbors an extensive microbiome, which has been shown to differ in patients with autoimmune diagnoses. Intracellular microbes slow innate immune defenses by dysregulating the vitamin D nuclear receptor, allowing pathogens to accumulate in tissue and blood. Molecular mimicry between pathogen and host causes further dysfunction by interfering with human protein interactions. Autoantibodies may well be created in response to pathogens. The catastrophic failure of human metabolism observed in autoimmune disease results from a common underlying pathogenesis - the successive accumulation of pathogens into the microbiome over time, and the ability of such pathogens to dysregulate gene transcription, translation, and human metabolic processes. Autoimmune diseases are more likely passed in families because of the inheritance of a familial microbiome, rather than Mendelian inheritance of genetic abnormalities. We can stimulate innate immune defenses and allow patients to target pathogens, but cell death results in immunopathology.

A Systematic Review and Meta-Analysis of the Diagnostic Accuracy of Anti-Heat Shock Protein 70 Antibodies for the Detection of Autoimmune Hearing Loss

We reviewed case-control studies concerning the diagnostic accuracy of Heat Shock Protein 70 (Hsp-70) auto antibodies in the detection of immunomediated inner ear disease. We searched for relevant articles published in English language on PubMed and Scopus up to December 2011. A quality assessment of the retrieved articles was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) 2 tool. Pooled data on the accuracy of the test were calculated, where possible. Three articles were deemed eligible. Among them, 2 evaluated the relationship between Hsp-70 and immunomediated inner ear disease by using the Western blot, whereas one report used the enzyme-linked immunosorbent assay method. Pooled sensitivity of Western blot test for Hsp-70 was 0.70 (95% confidence interval [CI], 0.59-0.80), with a large heterogeneity (I = 72.7%), and pooled specificity was 0.98 (95% CI, 0.87-1.00), with an I of 61.0%. Pooled positive likelihood ratios (LR) was 14.7 (95% CI, 2.1-104.1; I = 31.4%), and pooled negative LR was 0.32 (95% CI, 0.10-0.70; I = 78.8%). Sensitivity and specificity of enzyme-linked immunosorbent assay test for Hsp-70 auto antibodies was 0.85 (95% CI, 0.55-0.98) and 0.98 (95% CI, 0.86-1.00). Risk of bias was performed by using QUADAS 2 tool, with high scores obtained for patient selection and index test domains and low for the applicability criterion. This review shows that studies on autoimmune hearing loss diagnosis based on the detection of Hsp-70 autoantibodies used different inclusion and methodologic criteria and are affected from potential bias. Additional studies are actually required to identify an accurate laboratory diagnostic method for the autoimmune hearing loss.

Surface-activated microtiter-plate microarray for simultaneous CRP quantification and viral antibody detection

Microarrays are widely used in high-throughput DNA and RNA hybridization tests and recently adopted to protein and small molecule interaction studies in basic research and diagnostics. Parallel detection of serum antibodies and antigens has several potential applications in epidemiologic research, vaccine development, and in the diagnosis of allergies, autoimmunity, and infectious diseases. This study demonstrates an immobilization method for immunoassay-based microarray in conventional 96-well polystyrene plates for a serologic diagnostic method combined with quantitative C-reactive protein (CRP) assay. A synthetic peptide (HIV-1), a recombinant protein (Puumala hantavirus nucleocapsid), and purified virus preparations (Sindbis and adenoviruses) were used as antigens for virus-specific antibody detection and monoclonal anti-CRP antibody for antigen detection. The microarray was based on conventional enzyme immunoassays and densitometry from photographed results. Peptide and recombinant antigens functioned well, while whole virus antigens gave discrepant results in 1 out of 23 samples from the reference method, tested with human sera with various antibody responses. The CRP results were in concordance in the concentration range 0.5–150 mg/L with 2 commercially available CRP assays: ReaScan rapid test (R2 = 0.9975) and Cobas 6000 analyzer (R2 =0.9595). The results indicate that microtiter plates provide a promising platform for further development of microarrays for parallel antibody and antigen detection.

PP046. Adherence to exercise with bicycle during pregnancy in women with risk of preeclampsia

Physical activity (PA) has been proposed as an important part of hypertension's treatment and has been studied as a possibility for the prevention of preeclampsia (PE) and its complications. PA is recommended during pregnancy because it may be beneficial to maternal health. However, some studies relate the difficulty in adherence to exercise during pregnancy. The objective of this study was to evaluate the adherence to exercise with bicycle in pregnant women with risk of preeclampsia development and characterize these pregnants. This is a secondary analysis of a randomized clinical trial at the Women's Hospital Dr. José Aristodemo Pinotti - CAISM/Unicamp, Brazil. We enrolled 116 pregnant women presenting with chronic hypertension (CH), previous PE or both factors associated (risk of PE development). Women from 12 to 20 gestational weeks were selected from the prenatal outpatient clinic and randomly allocated to the study (SG) or non-interventional group (NIG). Women at the SG performed exercise using stationary bicycle (horizontal bench model) during 30min, once a week, under a physical therapist supervision. The HR was maintained at 20% above resting heart rate and up to 140 beats per minute, and the BP was evaluated before and after exercise. The NIG followed regular prenatal routine with weekly returns for HR and BP measurements. We analyzed the adherence of the SG to exercise with bicycle and their sociodemographic and clinical characteristics. We invited 152 pregnants to participate and 33 (21.7%) refused. 116 pregnants were randomized and 58 were allocated to the SG. The mean age was 31.7±6.2 and mean of Body Mass Index (BMI) was 34.9±7.9kg/m(2). Previous PE were prevalent in 16 (27.6%) pregnant, CH in 51 (87.9%) pregnant and 9 (15.5(10.5%) pregnants relate to exercise before pregnancy. The average sessions performed by the SG using stationary bicycle were 9.24±7.03. That those who realized less than the mean session of the SG 14 had discontinued, 3 changed the prenatal city, 4 had TPP, 3 had difficulty in controlling blood pressure, 1 had autoimmune hepatitis diagnosis and 1 had fetal malformation. Considering the sociodemographic and clinical characteristics of these 27 the majority were obese and had had CH, they were not used to practice any type of exercise before pregnancy. Most of them were not primiparous, also had more children at home and found difficul to find time for exercise. The majority did not live next to our center. The majority of our population were obese, sedentary before pregnancy and with CH. In this study exercise, performed once a week, using stationary bicycle in pregnant women of high risk PE, seems to be difficult.

Outcome of acute myeloid leukemia in patients with a history of autoimmune disease.

6579 Background: Increased risks of solid and lymphoid malignancies are described in patients with autoimmune (AI) disease. The association between AI disease, AI treatment (particularly anti-TNF therapy), and AML is less established. Moreover, the pathologic characteristics of AML in this population have not been evaluated. Here we describe our AML experience in patients with prior AI disease. Methods: Patients with AML from 1992 to 2011 were identified from our database, and AI disorder was verified through chart review. Patients were included if they had an AI disorder that required systemic treatment, and diagnosed &gt; 1 year prior to AML. Patients were excluded if details including the year of AI diagnosis or treatment(s) received were not documented. A total of 22 patients were included for analysis. Results: Median age at AML diagnosis was 59 years (range 32 – 78), 4 (18%) were men. 10 (48%) had received an anti-TNF agent, for a median duration of 30 months (range 2 – 120). Median latency from AI diagnosis to AML was 9.4 yrs. All FAB subtypes were represented except M0 and M6, 9 (41%) had M4 or M5 disease. 10/21 patients (45%) had normal cytogenetics, and 5 had favorable cytogenetics (2 with acute promyelocytic leukemia (APML)). Standard induction was given to 19 patients, and APML-directed therapy for those with APML. One patient received an autologous transplant in CR1, and 5 an allogeneic transplant (1 in CR1, 4 in CR2). 9 patients are alive in CR1. 13 relapsed, and 4 (31%) are alive in CR2 or CR3 (3 following allogeneic transplant in later CR). Median OS was 68.1 months. In univariate analysis, factors associated with OS were cytogenetics, FAB subtype, and gender. Anti-TNF therapy may be associated with poorer prognosis; this was not statistically significant. Median OS was 14.1 months for poor, 68.1 months for intermediate, and not reached for favorable risk cytogenetics. Conclusions: Median OS was higher (&gt; 5 years) than expected. Younger age and an increased incidence of favorable risk AML may account for this finding: whether this is a meaningful biologic association or stochastic event can only be verified with larger studies. Our observations do not support a label of “secondary leukemia” or therapy-related neoplasm in this population.

History of autoimmunity to predict clinical response to DNA methyltransferase inhibitors (DNMTI) in myelodysplastic syndromes (MDS), and MDS-derived acute myeloid leukemias (AML).

6629 Background: MDS is comprised of a heterogeneous group of clonal myeloid disorders. Chronic immune stimulation has been reported as a trigger for the development of a subset of MDS, with increased autoreactive cytotoxic T cells present in the bone marrow. Autoimmunity has been associated with MDS and other marrow failures. DNMTIs, 5-azacytidine and decitabine, are approved for the treatment of MDS. In addition to epigenetic impacts, these agents may have immunomodulatory effects, including augmentation of MAGE-related anti-tumor response. These reports and clinical observations led us to hypothesize that MDS patients with a history of autoimmunity may be more responsive to DNMTIs. Methods: To identify patients with MDS, a retrospective database review (2007-2011) was performed at Johns Hopkins Hospital (JHH) and Massachusetts General Hospital (MGH). The MGH data also included those with AML whose disease had progressed from MDS. Past medical history of autoimmune disorders, diagnosis, blood counts, flow cytometry and cytogenetics were reviewed. Patients with aplastic anemia, paroxysmal nocturnal hemoglobinuria or non-malignant etiologies of cytopenia were excluded. Patients with MDS were further studied if they were treated with DNMTI. Results: Of 137 patients with MDS or MDS/AML, 23 had a documented history of autoimmunity in the medical record. Of these, 15 (65.2%) experienced a response to therapy as defined by the International Working Group. Of 114 patients without a documented history of autoimmunity, 34 (29.8%) achieved a response during therapy, a significantly lower percentage as compared to those with autoimmune conditions (p-value 0.002, t-test). The majority of responding patients with a history of autoimmunity displayed a normal karyotype (9 of 15 patients). Conclusions: A history or co-presence of an autoimmune disorder may predict a high likelihood of achieving a clinical response to DNMTIs. Correlative studies in this unique population of patients with MDS and MDS/AML and prospective clinical studies are needed to improve our understanding of the possible mechanism of action of DNMTIs in these patients.

Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases

To assess the prevalence of concurrent extrahepatic autoimmune diseases in patients with autoimmune hepatitis (AIH)/primary biliary cirrhosis (PBC) overlap syndrome and applicability of the 'mosaic of autoimmunity' in these patients. The medical data of 71 AIH/PBC overlap patients were evaluated for associated autoimmune diseases. In the study population, 31 (43.6%) patients had extrahepatic autoimmune diseases, including autoimmune thyroid diseases (13 patients, 18.3%), Sjögren syndrome (six patients, 8.4%), celiac disease (three patients, 4.2%), psoriasis (three patients, 4.2%), rheumatoid arthritis (three patients, 4.2%), vitiligo (two patients, 2.8%), and systemic lupus erythematosus (two patients, 2.8%). Autoimmune hemolytic anemia, antiphospholipid syndrome, multiple sclerosis, membranous glomerulonephritis, sarcoidosis, systemic sclerosis, and temporal arteritis were identified in one patient each (1.4%). A total of 181 autoimmune disease diagnoses were found in our patients. Among them, 40 patients (56.4%) had two, 23 (32.3%) had three, and eight (11.3%) had four diagnosed autoimmune diseases. A large number of autoimmune diseases were associated with AIH/PBC overlap patients. Therefore, extended screening for existing autoimmune diseases during the routine assessment of these patients is recommended. Our study suggests that the concept of 'mosaic of autoimmunity' is a valid clinical entity that is applicable to patients with AIH/PBC overlap syndrome.

Prevalence of Patients with Multiple Neurological Autoimmune Diagnoses (P03.155)

Objective: To assess the prevalence of patients with multiple neurological autoimmune diagnoses, including “orphan” autoimmune conditions. Background The fact that there are patients with more than one autoimmune diagnosis is appreciated, but quantification of prevalence has been limited. The number of patients with a rare or “orphan” autoimmune disease, by itself, is challenging to assess; therefore, the prevalence of patients with more than one of these conditions is not well understood. Design/Methods: We conducted a retrospective analysis from a geographically-diverse administrative claims database from one of the largest insurers in the US, to assess the prevalence of 12 predefined autoimmune disorders. The prevalence of patients with more than one autoimmune diagnosis was then quantified. Results: Over 38 million enrollees were identified in the database during the period 1 Jan 2001 to 31 Dec 2008. Of these, 444,157 (1.2%) were identified as adults having received at least one autoimmune disorder diagnosis. Once additional methodological criteria were applied to ensure robustness for further analysis, 51,782 adult autoimmune patients remained. These patients were diagnosed with 57,983 autoimmune conditions, representing a multiple diagnosis overlap of 12.0%. The most prevalent diagnosis combination was Dermatomyositis with Polymyositis (40.7% of Dermatomyositis cases); outside of the myosites, patients diagnosed with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (65.0%) or Stiff person syndrome (60.8%) were most likely to have an additional autoimmune diagnosis. The most prevalent condition associated with Multiple Sclerosis was Guillain-Barre syndrome (9.7% of MS patients). A substantial proportion of Myasthenia Gravis patients had also received a diagnosis of MS (11.5%) or rheumatoid arthritis (8.9%). Conclusions: There is a significant prevalence of patients with multiple autoimmune disorder diagnoses in the US; often one or more of those disorders are “orphan” in nature. Supported by: Talecris Biotherapeutics. Talecris Biotherapeutics was acquired by Grifols Inc. effective June 1, 2011. Disclosure: Mr. Crescenzi has received personal compensation for activities with Grifols Inc. as an employee. Mr. Crescenzi has received research support from Talecris Biotherapeutics. Dr. Souayah has received personal compensation for activities with Walgreens as a consultant. Dr. Souayah has received research support from Talecris.

Routine use of Zenit RA, a novel chemiluminescent immunoanalyzer in autoimmune disease diagnosis.

The detection of antibodies is useful to diagnose and/or to classify autoimmune diseases as connective tissue diseases and vasculitis. Zenit RA is a fully automated immunoanalyzer. The aim of this study was to compare the predictive and discriminative performance of the Zenit RA anti-cyclic citrullinated peptide (CCP), anti-cardiolipin (aCL) and anti-β 2 glycoprotein 1 (aB2GP1) tests to conventional ELISAs on clinically well-defined groups of patients and to daily evaluate the determination of anti-extractable nuclear antigen (ENA), anti-double stranded DNA (dsDNA), anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies in a hospital laboratory. Reagents available on Zenit RA analyzer exhibit good diagnostic performances, regarding sensitivity, specificity, positive and negative predictive values. Global agreements between Zenit RA and conventional tests were from 90 to 98 % (Kappa-values ranging 0.56–0.94): 96 % for anti-CCP, 90–94 % for aCL and aB2GP1, 94 % for anti-dsDNA, 97 % for anti-ENA, 98 % for anti-MPO and 95 % for anti-PR3 antibodies. Zenit RA analyzer is easy to rapidly detect the most common autoantibodies in autoimmune diseases. This system has a potential to provide clinically useful data within a short time. Because of the flexibility of its work modalities, it is well adapted to determine antigenic specificities in daily practice.

Gastric Autoimmunity in Children and Adolescents with Type 1 Diabetes: A Prospective Study

Background/Aims: Type 1 diabetes (T1DM) is associated with gastric autoimmunity, which is characterized by the presence of parietal cell antibodies (APCA). We investigated gastric autoimmunity prevalence in T1DM children, its manifestations, determinants and association with thyroid gland (anti-Tg, anti-TPO) and pancreatic β-cell autoimmunity (anti-GAD) at baseline and 4 years later. Methods: The initial cohort (D1) included 97 children with T1DM. At follow-up after 4 years (D2), 84.5% of participants were evaluated. We assessed APCA, anti-Tg, anti-TPO, and anti-GAD presence, as well as symptoms of gastritis. APCA-positive patients were evaluated with gastrin, B₁₂, ferritin levels and were submitted to gastroscopy. Results: Thyroid antibody positivity was increased among the APCA-positive patients. Four years later, among initially APCA-positive patients, 2/6 became APCA negative, while 4/6 developed high titers of APCA. On gastroscopy, 2 patients had chronic hypertrophic gastritis and one Helicobacter pylori gastritis. Conclusions: Gastric autoimmunity was associated with thyroid autoimmunity and anti-GAD persistence. After 4 years, the majority of APCA-positive patients developed high titers of APCA and mild symptoms of gastritis. Thus, patients with T1DM, and in particular those with thyroid and/or pancreatic autoimmunity, should have periodic autoantibody screening for the early diagnosis and follow-up of gastric autoimmunity.

Autoimmune disorders in women with turner syndrome and women with karyotypically normal primary ovarian insufficiency

The higher prevalence of autoimmune diseases in women compared to men could be due to effects of ovarian hormones, pregnancy and/or the presence of a second X chromosome. To elucidate the role of these factors, we investigated the prevalence and spectrum of autoimmune diagnoses in women with primary ovarian insufficiency associated with X chromosome monosomy (Turner syndrome, TS, n = 244) and women with karyotypically normal (46,XX) primary ovarian insufficiency (POI, n = 457) in a prospective study, conducted at the National Institutes of Health. We compared the study group prevalence to normative data for the U.S. population of women. Chronic lymphocytic (Hashimoto’s) thyroiditis (HT) occurred in 37% of women with TS vs. 15% with POI (P < 0.0001); HT prevalence in both ovarian insufficiency groups significantly exceeded that in U.S. population of women (5.8%). Inflammatory bowel (IBD, 4%) and celiac disease (CD, 2.7%) were significantly increased in TS, but not in POI. No other autoimmune diagnosis, including Graves’ disease or Type 1 diabetes appears to be significantly increased in either group. Women with TS had higher pro-inflammatory IL6 and TGF β1 levels (p < 0.0001 for both), and lower anti-inflammatory IL10 and TGF β2 levels (p < 0.005 for both) compared to POI and to normal volunteers. Lifetime estrogen exposure and parity were significantly lower in TS compared to POI, which were in turn lower than the general population of women. The finding that lymphocytic thyroiditis is greatly increased in both women with TS and POI suggests that factors associated with ovarian insufficiency per se promote this form of autoimmunity. The absence of a normal second X-chromosome further contributes to increased autoimmunity in TS.