Types Of Autoantibodies Research Articles

AB0427 Clinical and laboratory findings in patients with late-onset sle and correlations with il6 concentrations

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune rheumatic disease that usually develops in women aged 18-50 years. It is known that age at onset modifies the clinical manifestations of SLE,...

Complement system in SLE as a target for antibodies.

SLE is characterized by overproduction of various types of autoantibodies. Under certain circumstances, antibodies targeting some of the neoepitopes of the complement system can be seen. The most studied among antibodies directed against a component of the complement system is anti-C1q. Anti-C1q antibodies are present in approximately one third of the patients with lupus, who often have high clinical disease activity and in particular renal involvement. In the presence of high titers of anti-C1q antibodies also the levels of C1q and C3 and C4 components of the complement system are also usually low. The presence of the anti-C1q antibodies is not limited or specific just for SLE or lupus nephritis. For the first time, they were described in HUVS (Hypocomplementemic Urticarial Vasculitis Sydrome), later in Felty´s syndrome, rheumatoid vasculitis, hepatitis C, poststreptococcal glomerulonephritis or aging population.

A7.14 IRF5Polymorphisms in Systemic Sclerosis

<h3>Introduction</h3> The transcription factor interferon regulatory factor 5 (IRF-5) plays a key role in the Toll-like receptor signalling pathway, and activation of the type I interferon response. As well as being associated with a number of other rheumatological diseases, including systemic lupus erythematosus and rheumatoid arthritis, <i>IRF5</i> has been identified as a candidate gene for systemic sclerosis (SSc) in a number of genome wide association studies. Although this finding has been replicated in several different studies, there has been variation in the single nucleotide polymorphisms (SNPs) tested, thereby making it difficult to determine which <i>IRF5</i> SNP(s) may be playing a role in susceptibility to SSc. We therefore tested a number of <i>IRF5</i> SNPs in a UK based population with the aim of elucidating the true causal variant(s). <h3>Materials and Methods</h3> To investigate involvement of this gene in susceptibility to SSc, UK Caucasian patients and controls (SSc n = 465, controls n = 416) were genotyped using commercially available TaqMan assays. The <i>IRF5</i> SNPs Rs4728142, Rs2004640, Rs10954213, and Rs10488631, previously reported to be associated with SSc, were selected for investigation. The presence of pulmonary fibrosis was defined as a forced vital capacity &lt;75% and/or the presence of fibrosis on chest imaging. <h3>Results</h3> The allele frequencies of each of the four <i>IRF5</i> SNPs were not significantly different (using Bonferroni correction for multiple testing) in the healthy controls and patients with SSc (Rs4728142: 0.52/0.50, Rs2004640: 0.56/0.60, Rs10954213: 0.37/0.35, Rs10488631: 0.12/0.14). There was also no significant difference found for any of the SNPs when the SSc patients were subdivided according to disease type (limited/diffuse), presence of pulmonary fibrosis, or auto-antibody type. <h3>Conclusions</h3> In contrast to previously published studies we did not detect a significant difference in allele frequency between patients with SSc and healthy control individuals for any of the four <i>IRF5</i> SNPs tested. However, due to the modest cohort sizes available, this study has limited power and therefore may have been unable to detect allele frequency differences with small effects. This study therefore will be repeated with larger cohorts in order to validate these results.

Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non–rheumatoid arthritis controls

The significance of non-rheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. The aim of this study was to assess associations of autoantibodies with autoimmune risk alleles and with clinical diagnoses from the electronic medical records (EMRs) among RA cases and non-RA controls. Data on 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry were obtained from the EMRs of 2 large academic centers. The levels of anti-citrullinated protein antibodies (ACPAs), antinuclear antibodies (ANAs), anti-tissue transglutaminase antibodies (AGTAs), and anti-thyroid peroxidase (anti-TPO) antibodies were measured. All subjects were genotyped for autoimmune risk alleles, and the association between number of autoimmune risk alleles present and number of types of autoantibodies present was studied. A phenome-wide association study (PheWAS) was conducted to study potential associations between autoantibodies and clinical diagnoses among RA cases and non-RA controls. The mean ages were 60.7 years in RA cases and 64.6 years in non-RA controls. The proportion of female subjects was 79% in each group. The prevalence of ACPAs and ANAs was higher in RA cases compared to controls (each P < 0.0001); there were no differences in the prevalence of anti-TPO antibodies and AGTAs. Carriage of higher numbers of autoimmune risk alleles was associated with increasing numbers of autoantibody types in RA cases (P = 2.1 × 10(-5)) and non-RA controls (P = 5.0 × 10(-3)). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjögren's/sicca syndrome in RA cases. The increased frequency of autoantibodies in RA cases and non-RA controls was associated with the number of autoimmune risk alleles carried by an individual. PheWAS of EMR data, with linkage to laboratory data obtained from blood samples, provide a novel method to test for the clinical significance of biomarkers in disease.

Autoantibodies in liver disease: important clues for the diagnosis, disease activity and prognosis.

It has been well established that numerous kinds of autoantibodies have been detected in liver disease. Some kinds of autoantibodies may be helpful in the diagnosis of autoimmune liver diseases including autoimmune hepatitis, primary biliary cirrhosis or primary sclerosing cholangitis. However, these autoantibodies are present even in sera of patients with viral hepatitis, drug-induced hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and hepatocelluar carcinoma as well as in sera of patients with autoimmune liver diseases. Other kinds of autoantibodies are recognized as predictive hallmarks for disease activity or prognosis in liver diseases. On the other hand, treatment with interferon initiates the production of several types of autoantibodies in patients with chronic hepatitis C virus infection. Some of autoantibodies induced by interferon may postulate the treatment outcome in those patients. Recent studies also revealed the close correlation between oxidative stress and the production of autoantibodies in liver diseases. This article primarily reviews the recent advances of autoantibodies in the liver diseases and discusses the clinical significance of these autoantibodies.

Automation Highlights from the Literature

Automation Highlights from the Literature

Protamine-containing insulins are strong risk factors, and human insulin analogues are possible risk factors for insulin autoantibody: case-control study

Insulin autoantibody is known to cause fluctuation of blood glucose. We examined whether medications for diabetes are risk factors for insulin autoantibody. Especially, we examined the associations between types of insulin and insulin autoantibody. We performed a case-control study. From April 2005 to March 2010, insulin autoantibody was measured 273 times in 217 patients in our hospital. Insulin autoantibody was positive (greater than 10%) 53 times in 19 patients (case), and was negative 220 times in 198 patients (control). Oral hypoglycemic agents were not risk factors for insulin autoantibody; the odds ratio was 0.0. In contrast, insulin use was a significant risk factor for insulin autoantibody; the odds ratio (95% confidence interval) was 56.3 (7.3-432.5). As for the types of insulin and insulin autoantibody, human insulins without protamine were not risk factors; the odds ratio was 0.0. For protamine-containing insulins, the odds ratio and adjusted odds ratio (adjusted by age, gender, and disease: type 1 diabetes mellitus, type 2 diabetes mellitus, and no diabetes) were 35.3 (9.6-129.5) and 29.6 (7.6- 115.4), respectively. For Aspart-containing insulins, they were 6.2 (2.2-17.9) and 3.8 (1.2- 12.0), respectively. For Glargine, they were 3.2 (0.6-16.7) and 1.3 (0.2-8.3), respectively. To decrease the problem of insulin antibody, avoiding the use of protamine-containing insulins and avoiding the use of human insulin analogues might be preferable for the patients with diabetes.

Evidence on the pathogenic role of auto-antibodies in acute cardiovascular diseases

Atherothrombosis is the major determinant of acute ischaemic cardiovascular events, such as myocardial infarction and stroke. Inflammatory processes have been linked to all phases of atherogenesis In particular, the identification of autoimmunity mediators in the complex microenvironment of chronic inflammation has become the focus of attention in both early and advanced atherogenic processes. Auto-antibodies against self-molecules or new epitopes generated by oxidative processes infiltrate atherosclerotic plaques and were shown to modulate the activity of immune cells by binding various types of receptors. However, despite mounting evidence for a pathophysiological role of autoantibodies in atherothrombosis, the clinical relevance for circulating autoantibodies in cardiovascular outcomes is still debated. This review aims at illustrating the mechanisms by which different types of autoantibodies might either promote or repress atherothrombosis and to discuss the clinical studies assessing the role of auto-antibodies as prognostic biomarkers of plaque vulnerability.

Human APECED; a Sick Thymus Syndrome?

Loss-of-function mutations in the Autoimmune Regulator (AIRE) gene cause a rare inherited form of autoimmune disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, also known as autoimmune polyglandular syndrome type 1. The patients suffer from multiple endocrine deficiencies, the most common manifestations being hypoparathyroidism, Addison’s disease, hypogonadism, and secondary amenorrhea, usually accompanied by typical autoantibodies against the target tissues. Chronic mucocutaneous candidiasis is also a prominent part of the disease. The highest expression of AIRE is found in medullary thymic epithelial cells (mTECs). Murine studies suggest that it promotes ectopic transcription of self antigens in mTECs and is thus important for negative selection. However, failed negative selection alone is not enough to explain key findings in human patients, necessitating the search for alternative or additional pathogenetic mechanisms. A striking feature of the human AIRE-deficient phenotype is that all patients develop high titers of neutralizing autoantibodies against type I interferons, which have been shown to downregulate the expression of interferon-controlled genes. These autoantibodies often precede clinical symptoms and other autoantibodies, suggesting that they are a reflection of the pathogenetic process. Other cytokines are targeted as well, notably those produced by Th17 cells; these autoantibodies have been linked to the defect in anti-candida defenses. A defect in regulatory T cells has also been reported in several studies and seems to affect already the recent thymic emigrant population. Taken together, these findings in human patients point to a widespread disruption of T cell development and regulation, which is likely to have its origins in an abnormal thymic milieu. The absence of functional AIRE in peripheral lymphoid tissues may also contribute to the pathogenesis of the disease.

Primary mixed-type autoimmune hemolytic anemia concomitant with acute splanchnic venous thrombosis of idiopathic origin in a young woman: an unexplained association

TO THE EDITOR: Mixed autoimmune hemolytic anemia (AIHA) is defined by the presence of both warm and cold types of autoantibodies [1, 2]. The diagnosis is based on the detection of these autoantibodies by using a monospecific direct antiglobulin test; a positive test result shows a pattern of IgG and complement C3d along with the presence of cold agglutinins. Mixed AIHA may be of idiopathic origin or associated with an underlying disease [1]. Venous thromboembolism is a common complication of AIHA, although it is not often identified [3, 4]. In some instances, its occurrence may be related to coexistent antiphospholipid antibodies. However, the association of primary mixed AIHA with idiopathic acute splanchnic venous thrombosis (SVT), as we recently observed, represents an exceptional occurrence; thus far, it has been reported for AIHA only in conjunction with splenectomy [5], but has never been reported as a concomitant manifestation. In the present report, we describe the case of a 19-year-old woman who presented with diffuse abdominal pain and severe anemia. At admission, she presented with life-threatening medical conditions due to severe anemia and critical abdominal features. Her medical history was unremarkable. Findings on clinical images and laboratory parameters were consistent with an acute and severe hemolytic disorder; her Hb level had decreased to 3.9 g/dL, whereas the reticulocyte count, indirect bilirubin level, and lactate dehydrogenase concentration were elevated. On admission, the patient was transfused with packed red blood cells (12 units). A strongly positive result on direct antiglobulin test (IgG3 and C3d) was detected; the indirect antiglobulin test indicated a positive result at 4℃ and a negative result at 22℃ and 39℃ in the presence of a cold panagglutinin antibody (IgM). The concomitant acute abdominal condition was investigated by a comprehensive radiological work-up, including an abdominal echography and a body computed tomography scan, and revealed complete thrombosis of the portal and splenic veins as well as partial occlusion of the superior mesenteric vein. A diagnosis of mixed AIHA associated with SVT was made, and treatment with prednisone (1 mg/kg body weight/day) was promptly initiated; in addition, therapeutic subcutaneous Fraxiparine injections with warfarin were also administered. Additional laboratory investigations revealed no other causes of anemia and ruled out the presence of autoimmune disorders, infections, and liver diseases. Investigations into the possible causes for the development of the thrombosis, including all genetic and acquired abnormalities associated with hypercoagulability states, as well as those aimed to identify a possible underlying neoplastic etiology, did not provide any useful findings. Similarly, the presence of a paroxysmal nocturnal hemoglobinuria clone or abnormal Hb chains was ruled out. The patient was discharged with continued warfarin treatment with a fraxiparine bridge. However, based on the patient's decision, the warfarin treatment was subsequently discontinued, whereas the fraxiparine was maintained for only 6 months, after which a careful reevaluation showed complete SVT resolution and full vein recanalization in the splanchnic area. Moreover, based on the clinical response, the prednisone dose was adjusted and tapered until the minimal effective maintenance dose was reached; immunohematological evaluations were regularly repeated and indicated completely negative results. However, an AIHA recurrence was observed 6 months after the reduction of prednisone to the lowest dosage. At this time, a second line treatment of rituximab (375 mg/m2, 4 weekly courses) was given. A complete response by rituximab was achieved. At approximately 1 year after the primary diagnosis was made, the patient is doing well. As AIHA and acute SVT may have been the initial manifestations of underlying occult disorders, the patient is carefully and regularly evaluated to promptly diagnose any recurrence of her hematological complaints. Thus, we report a rare and unexplained association of primary mixed AIHA with acute SVT, both of idiopathic origin that simultaneously occurred in a young patient.

Comparison of the prevalence of islet autoantibodies according to age and disease duration in patients with type 1 diabetes mellitus.

PurposeThis study investigated the prevalence of islet autoantibodies in children and adults with T1DM according to their age and the duration of disease.MethodsWe measured the levels of islet autoantibodies, including antiglutamic acid decarboxylase antibody (anti-GAD Ab), and combined these with anthropometric measurements and laboratory tests of 137 patients newly diagnosed with T1DM during the last 20 years. The subjects were subdivided into four groups according to their age at the onset of the disease. We then compared the prevalence of islet autoantibodies in the different age groups with the duration of disease.ResultsAmong the 137 patients, 68.9% tested positive for islet autoantibodies (71.4% within 1 year; 67.7% after 1 year of the disease onset). Within 1 year of the onset of the disease, 66.3% of the patients were positive for the anti-GAD Ab, and 35.6% were positive for IAAs. The prevalence of islet autoantibodies was significantly higher in the prepubertal groups than in the postpubertal groups (80.0% vs. 58.3%). The rate of positive islet autoantibodies changed with the duration of disease, and it differed according to the type of autoantibody and the age of the patient.ConclusionThe rates of positive islet autoantibodies were significantly higher in younger than in older patients at the time of the diagnosis of the disease. The positive rates were significantly changed 1 year after the onset of the disease in the preschool and the children groups. So these findings suggest that we need to diagnose type 1B diabetes distinguished T2DM in aldolescent group, carefully.

Anti-centromere antibody is an independent risk factor for chronic kidney disease in patients with primary biliary cirrhosis

Anti-centromere antibody (ACA), a typical autoantibody of systemic sclerosis, is also detected in primary biliary cirrhosis (PBC). However, its pathogenic role is not fully understood. The aim of this study was to determine the association between ACA and kidney function in PBC. A cohort of 37 patients diagnosed as having PBC from July 2001 to November 2011 at Yokosuka Kyosai Hospital was retrospectively analyzed for a follow-up period of 12 months. The annual rate of estimated glomerular filtration rate (eGFR) decline within 1 year after the diagnosis was evaluated. The factors associated with eGFR decline were evaluated by linear regression analysis and logistic regression analysis. Overall, 37 PBC patients were included, of whom 12 (32%) had ACA. The patients with ACA had a lower eGFR (65.9 ± 19.9 vs. 80.3 ± 12.1 mL/min/1.73 m(2), P = 0.01), a higher likelihood of chronic kidney disease (CKD) (58 vs. 4%, P = 0.0005), and a higher rate of annual eGFR decline (-4.3 ± 5.1 vs. 0.2 ± 4.6 mL/min/year, P = 0.01) than those without ACA. Univariate regression analysis and multivariate regression analysis adjusted for potential cofounders including age, eGFR, sex, diabetes mellitus, and hypertension showed that ACA was associated with eGFR decline (P = 0.011 and 0.017, respectively). Multivariate logistic regression analysis adjusted for these cofounders showed that ACA was associated with eGFR decline less than -4 mL/min/year (odds ratio 7.21, 95% confidence interval 0.93-56.1, P = 0.059). ACA is an independent risk factor for CKD in PBC. Evaluation of ACA and kidney function is necessary to prevent CKD progression in PBC patients.

Prevalence and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis

The clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis is unclear. The objective of this study was to determine the frequency and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis. We measured an extensive panel of autoantibodies (including rheumatoid factor, anti-cyclic citrullinated peptide, and anti-nuclear antibodies by immunofluorescence) associated with connective tissue disease or vasculitis in a cohort of well-characterized patients with idiopathic pulmonary fibrosis (n=67). The prevalence of circulating autoantibodies was compared between idiopathic pulmonary fibrosis patients and healthy controls (n=52). We compared the clinical characteristics of patients with and without circulating autoantibodies, and analyzed the relationship between autoantibody positivity and transplant-free survival time. Positive autoantibodies were found in 22% of patients with IPF and 21% of healthy controls. There were no differences in the types of autoantibodies found between patients with idiopathic pulmonary fibrosis and healthy controls. Among patients with idiopathic pulmonary fibrosis, there were no significant differences in clinical characteristics between those with and without circulating autoantibodies. The presence of circulating autoantibodies was associated with longer transplant-free survival time on adjusted analysis, however the significance varied depending on which statistical model was used (HR 0.22-0.47, p value 0.02-0.17). The frequency of circulating autoantibodies in patients with idiopathic pulmonary fibrosis is no different compared to healthy controls, but may be associated with longer survival.

Thyroid autoimmunity

This overview of the thyroid autoimmunity in human presents the various facets of a very common pathology. Focus is rather on fundamental than clinical aspects, although some specific clinical situations are discussed. Epidemiology, pathophysiology and pathology of AITD are detailed. One of the peculiarities of AITD is that they express two opposed phenotypes, hypothyroid thyroiditis and hyperthyroid Graves' disease. The latter is characterised by the presence of a unique type of autoantibodies, the anti-TSH receptor antibodies. Those are capable to activate the TSH receptor leading to the gland hypertrophy and hyperfunction. On the contrary, the autoimmune thyroiditis processus progressively and slowly tends to the necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis, postpartum thyroiditis and silent thyroiditis are also described. This review, which is not exhaustive, aims at providing a wide scope on the AITD, a basis from which the interested reader or the specialist will be able to find routes towards deeper knowledge.

Zinc Transporter 8 Autoantibodies and Their Association WithSLC30A8andHLA-DQGenes Differ Between Immigrant and Swedish Patients With Newly Diagnosed Type 1 Diabetes in the Better Diabetes Diagnosis Study

We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.

Improvement of protein immobilization for the elaboration of tumor-associated antigen microarrays: Application to the sensitive and specific detection of tumor markers from breast cancer sera

There is an urgent need to identify relevant tumor markers showing high sensitivity and specificity for early diagnosis and prognosis of breast cancer. Protein microarrays have demonstrated to be cost-effective, high through-put and powerful tools for screening and identifying tumor markers with only minute samples. Autoantibodies directed against tumor-associated antigens (TAAs) were shown to be relevant tumor markers. However, due to the variability of immune response from one individual to another and depending on the type of cancer, detection of only one type of anti-TAA autoantibody is not sufficient to give a reliable and precise diagnosis. It is necessary to use a set of several TAAs for determining specific autoimmune profiles. Therefore, combining various TAAs on different surfaces could improve sensitivity and specificity for anti-TAA autoantibody detection. Herein a panel of 10 proteins, including well-known tumor-associated antigens (TAAs) and potential new biomarkers of breast cancer, were immobilized onto microstructured microarray under optimized conditions (spotting pH buffer, surface chemistry, blocking procedure), in order to determine an autoimmune signature of breast cancer. Sera from 29 breast cancer patients and 28 healthy donors were screened in sandwich immunoassays on the miniaturized system to detect the eventual presence of anti-TAAs autoantibodies. Results indicated that the detection level of each anti-TAA autoantibody in a given serum sample was strongly dependant on the surface chemistry. Combining five TAAs (p53, Hsp60, Hsp70, Her2-Fc, NY-ESO-1) on two different surface chemistries (NHS and APDMES) allowed the significant detection of more than 82% breast cancer sera.

Current state of diagnostic technologies in the autoimmunology laboratory

The methods for detecting and measuring autoantibodies have evolved markedly in recent years, encompassing three generations of analytical technologies. Many different immunoassay methods have been developed and used for research and laboratory practice purposes, from the early conventional (or monoplex) analytical methods able to detect single autoantibodies to the more recent multiplex platforms that can quantify tens of molecules. Although it has been in use for over 50 years, indirect immunofluorescence remains the standard method for research on many types of autoantibodies, due to its characteristics of diagnostic sensitivity and also to recent technological innovations which permit it a greater level of automation and standardization. The recent multiplex immunometric methods, with varying levels of automation, present characteristics of higher diagnostic accuracy, but are not yet widely diffused in autoimmunology laboratories due to the limited number of autoantibodies that are detectable, and due to the high cost of reagents and systems. Technological advancement in autoimmunology continues to evolve rapidly, and in the coming years new proteomic techniques will be able to radically change the approach to diagnostics and possibly also clinical treatment of autoimmune diseases. The scope of this review is to update the state of the art of technologies and methods for the measurement of autoantibodies, with special reference to innovations in indirect immunofluorescence and in multiple proteomic methods.

Gene expression changes in human islets exposed to type 1 diabetic serum

A major obstacle to the success of islet cell transplantation as a standard treatment for labile type 1 diabetes mellitus is the immediate loss of up to 70% of the transplanted islet mass. Activation of the complement cascade and coagulation factors has been implicated in initiating the destruction of the islet graft. In this study, we analyzed the gene expression changes in islet cells following exposure to type 1 diabetes mellitus serum (T1DM). Isolated human pancreatic islet cells were cultured for 2 d to stabilize islet cell gene expression. Cultured islets were divided into three groups for treatment as follows: group 1 was treated with autologous donor serum, while groups two and three were treated with sera from ABO-matched allogeneic donors or autoantibody positive type 1 diabetic patient, respectively. Complement was detected using anti-C3 FITC and CH50 assay. Islet gene expression was analyzed using Illumina micro-array technology. Results were confirmed using real-time PCR. Immunofluorescent imaging demonstrated complement deposition only in the T1DM condition. Gene array and class prediction analysis generated a list of 50 genes that were able to predict the effect of T1DM serum on islets. Quantitative PCR corroborated microarray results. Both techniques demonstrated upregulation of MMP9 (243%), IL-1β (255%), IL-11 (220%), IL-12A (132%), RAD (343%) and a concomitant downregulation of IL-1RN (64%) in islets treated with T1DM serum. Islets treated with T1DM serum overexpressed genes associated with angiogenesis while decreasing transcription of genes that protect islets from inflammatory cytokines and reactive oxygen species.

Trichinella spiralis shares epitopes with human autoantigens

Like other helminths, Trichinella spiralis has evolved strategies to allow it to survive in the host organism, including the expression of epitopes similar to those present in either expressed or hidden host antigens. To identify T. spiralis-derived antigens that are evolutionarily conserved in the parasite and its host and that could be responsible for its evasion of the host immune response, we examined the reactivity of six different types of autoantibodies to T. spiralis larvae from muscle. T. spiralis antigens that share epitopes with human autoantigens were identified by assessing the cross-reactivity of autoantibody-containing serum samples with T. spiralis antigens in the absence of specific anti-parasite antibodies. Of the 55 autoantibody-containing human serum samples that we analysed by immunohistological screening, 24 (43.6%) recognised T. spiralis muscle larvae structures such as the subcuticular region, the genital primordium or the midgut. Using Western blots, we demonstrated that the same sera reacted with 24 protein components of T. spiralis muscle larvae excretory-secretory L1 antigens. We found that the human autoantibodies predominantly bound antigens belonging to the TSL1 group; more specifically, the autoantibody-containing sera reacted most frequently with the 53-kDa component. Thus, this protein is a good candidate for further studies of the mechanisms of T. spiralis-mediated immunomodulation.

Excessive Blinking and Ataxia in a Child With Occult Neuroblastoma and Voltage-Gated Potassium Channel Antibodies

A previously healthy 9-year-old girl presented with a 10-day history of slowly progressive unsteadiness, slurred speech, and behavior change. On examination there was cerebellar ataxia and dysarthria, excessive blinking, subtle perioral myoclonus, and labile mood. The finding of oligoclonal bands in the cerebrospinal fluid prompted paraneoplastic serological evaluation and search for an occult neural crest tumor. Antineuronal nuclear autoantibody type 1 (anti-Hu) and voltage-gated potassium channel complex antibodies were detected in serum. Metaiodobenzylguanidine scan and computed tomography scan of the abdomen showed a localized abdominal mass in the region of the porta hepatis. A diagnosis of occult neuroblastoma was made. Resection of the stage 1 neuroblastoma and treatment with pulsed corticosteroids resulted in resolution of all symptoms and signs. Excessive blinking has rarely been described with neuroblastoma, and, when it is not an isolated finding, it may be a useful clue to this paraneoplastic syndrome. Although voltage-gated potassium channel complex autoimmunity has not been described previously in the setting of neuroblastoma, it is associated with a spectrum of paraneoplastic neurologic manifestations in adults, including peripheral nerve hyperexcitability disorders.