Autoimmune Markers Research Articles

Inflammatory factors and immunophenotypes in adjustment disorders

To identify inflammatory and autoimmune markers (enzymatic activity of leukocyte elastase (LE), functional α1-proteinase inhibitor (α1-PI), the level of autoantibodies to neurospecific antigens S100b and myelin basic protein (MBP)) as well as phagocytic activity of blood neutrophils of patients with disorders of adaptation, to determine certain immunophenotypes and analyze their possible relationships with disease characteristics. The study included 40 patients with adaptation disorders, mostly women. Diagnostic evaluation and clinical qualification of patients was carried out in accordance with ICD-10: 'Adjustment disorder' (F43.2). The control group consisted of 23 individuals matched for age and sex with patients. The activity of LE and α1-PI was determined by spectrophotometry, and the levels of autoantibodies to S100b and MBP by ELISA, phagocytic activity by the absorptive capacity of neutrophils of peripheral blood of melamine-formaldehyde latex particles. In the total group of patients with adaptation disorders, increased enzymatic activity of LE and functional α1-PI was shown compared to controls (p<0.001 and p<0.0001, respectively). There were no differences in the level of autoantibodies to neuroantigens, and changes in phagocytic index (PhN) compared with the control, however the tendency to reduction of phagocytic number (PhN) was observed. Patients were stratified by leading psychopathological symptoms (predominance of asthenic-depressive or anxious-depressive symptoms, polymorphic symptomatology) and by immunophenotype: (A) inflammatory markers - in the range of control values, (B) - the increase compared to the control activity of both LE and α1-PI, (C) preferential increase in the activity of α1-PI only. The frequency of these immunophenotypes was similar within each of the clinical subgroups. The results suggest the involvement of inflammation in the pathogenesis of adjustment disorders due to stress factors. Various immunological variants differed by proportion of inflammatory markers were not associated with clinical symptoms.

Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers.

Objective The aim of this research was to analyze the expression profile of miR-155, miR-146a, and miR-326 in peripheral blood mononuclear cells (PBMC) of 47 patients with type 1 diabetes mellitus (T1D) and 39 control subjects, as well as the possible association with autoimmune or inflammatory markers. Subjects and methods Expression profile of miRs by means of qPCR using TaqMan probes. Autoantibodies and inflammatory markers by ELISA. Statistical analysis using bivariate correlation. Results The analysis of the results shows an increase in the expression of miR-155 in T1D patients in basal conditions compared to the controls (p < 0.001) and a decreased expression level of miR-326 (p < 0.01) and miR-146a (p < 0.05) compared T1D patients to the controls. miR-155 was the only miRs associated with autoinmmunity (ZnT8) and inflammatory status (vCAM). Conclusion Our data show a possible role of miR-155 related to autoimmunity and inflammation in Chilean patients with T1D.

Immune Response to Rotavirus and Gluten Sensitivity.

Rotavirus is a double-stranded RNA virus belonging to the family of Reoviridae. The virus is transmitted by the faecal-oral route and infects intestinal cells causing gastroenteritis. Rotaviruses are the main cause of severe acute diarrhoea in children less than 5 years of age worldwide. In our previous work we have shown a link between rotavirus infection and celiac disease. Nonceliac gluten sensitivity (NCGS) is emerging as new clinical entity lacking specific diagnostic biomarkers which has been reported to occur in 6–10% of the population. Clinical manifestations include gastrointestinal and/or extraintestinal symptoms which recede with gluten withdrawal. The pathogenesis of the disease is still unknown. Aim of this work is to clarify some aspects of its pathogenesis using a gene array approach. Our results suggest that NCGS may have an autoimmune origin. This is based both on gene expression data (i.e., TH17-interferon signatures) and on the presence of TH17 cells and of serological markers of autoimmunity in NCGS. Our results also indicate a possible involvement of rotavirus infection in the pathogenesis of nonceliac gluten sensitivity similarly to what we have previously shown in celiac disease.

DPP-4 INHIBITORS INCREASE THE INCIDENCE OF ARTHRITIS/ARTHRALGIA BUT DO NOT AFFECT AUTOIMMUNITY.

In August 2015, FDA published a black box declaring that DPP-4 inhibitors may cause severe joint pains. The impact on autoimmunity marker positivity of these drugs has not been comprehensively evaluated. We compared the incidence of arthritis/arthralgia in patients with T2DM who were using DPP-4 inhibitors and patients who were not using. A number of 93 DPP-4 inhibitor users and 107 non-users were included into the study. Arthritis/arthralgia were found in 41 of 93 (44.1%) DPP-4 inhibitor users and in 19 of 107 (17.8%) non-users (p<0.05). No inflammatory rheumatological condition was identified in 27 of 41 (65.9%) patients in DPP-4 inhibitor user group as well as in 13 of 19 (68.4%) patients in non-user group (p>0.05). After adjusting for gender the incidence for arthritis/arthralgia was significantly increased in the DPP-4 inhibitor user group (p value for any DPP-inhibitor <0.05). There was 3.77 times increased risk for arthritis/arthralgia in the DPP-4 inhibitor using group (p value= 0.001) and this risk increases 2.43 times for each year of DPP-4 inhibitor usage. Arthritis/arthralgia were more common among T2DM patients who were using DPP-4 inhibitors compared to non-users, but the seropositivity did not differ between DPP-4 inhibitor users and non-users.

Levamisole vs. Autoimmune Leukocytoclastic Vasculitis

Levamisole is a veterinary antihelminthic drug that, in the past, was a US Food and Drug Administration-approved drug in humans used to treat various cancers and rheumatoid arthritis because of its immunomodulating effects; however, it is not longer used in the United States since 2000, because of multiple adverse side effects including agranulocytosis and vasculitis. Drug-induced vasculitis is a challenging diagnosis. It is important to recognize that levamisole may not only induce ANCA-associated vasculitis but also other autoimmune markers abnormalities. This case discusses the possibility of levamisole-induced vasculitis and the need to pursue further testing to establish causality in ANCA-associated vasculitis. J Med Cases. 2018;9(1):19-20 doi: https://doi.org/10.14740/jmc2965w

Vitamin D in Hashimoto's thyroiditis and its relationship with thyroid function and inflammatory status.

Several studies have shown the correlation between vitamin D [25(OH)D] deficiency and thyroid autoimmunity and reducing of thyroid autoantibodies in patients with normal levels of vitamin D combining with thyroid hormone replacement. However, other authors not agree with this association. It is still unclear whether the low 25(OH)D levels are the result of HT disease or a part of its cause. We studied 88 patients with HT regarding vitamin D status and thyroid autoimmunity markers as well as the relationship with cytokines produced by Th1, Th2, and Th17 cells compared with a control group of 71 euthyroid healthy subjects. The present study demonstrated that vitamin D concentrations were similar in patients HT and the control group. The reduction of free T4 levels was a predictor of vitamin D insufficiency for Hashimoto's thyroiditis, but not for the control group. Lower concentrations of TNF-α was a predictor of lower levels of vitamin D. Differences in the association between HT and vitamin D insufficiency remain unresolved in the literature. The thyroid hormone status would play a role in the maintenance of vitamin D sufficiency, and its immunomodulatory role would influence the presence of autoimmune thyroid disease. The positive correlation between free T4 and vitamin D concentrations suggests that adequate levothyroxine replacement in HT would be an essential factor in maintaining vitamin D at sufficient levels.

Brucellosis mimic SLE

Brucellosis is an infectious disease with articular involvement. Brucellosis and rheumatologic disorders are difficult to discriminate between them in regions endemic to brucellosis. The autoantibody level in patients with brucellosis has been discussed in a few studies. In one study showed autoimmune processes in the pathogenesis of brucellosis . The purpose of this paper is to report a case of brucellosis that presented with positive autoimmune markers while negative Brucella agglutination test. Also the effectiveness of prednisolone in an acute phase.

Autoinflammatory phenotypes in Aicardi-Goutières syndrome with interferon upregulation and serological autoimmune features

In an Aicardi-Goutieres syndrome patient, cimetidine successfully controlled periodic fever with improved serum autoimmune marker levels, suggesting the presence of crosstalk between autoinflammation and autoimmunity in type I interferonopathy.

An Abortive Hepatocellular Carcinoma Presenting as Obstructive Jaundice

This is the case of an 80 year old Hispanic man that came to the emergency room due to right upper quadrant discomfort and yellowing of the skin for the past weeks. He also reported dark colored urine, clay color stools and a 30 pound weight loss. He was taking apixaban for chronic atrial fibrillation and had a prior cholecystectomy due to gallstones. He was jaundiced, the liver edge was palpable, and had right upper quadrant tenderness. Laboratory tests revealed hemoglobin of 11.1 mg/dL, thrombocytosis of 389 x 103, prolonged PT at 18.4 sec, bilirubin in 25 mg/dL, alkaline phosphatase of 1,079 u/L and elevated hepatic enzymes consistent with a cholestatic pattern. An abdominal CT with intravenous contrast demonstrated intrahepatic biliary ductal dilation with prominent distention of the common hepatic duct. A soft tissue density measuring 1.8 cm x 1.3 cm, was observed within the proximal common bile duct, which appeared to be the cause of the obstruction (Figure 1). An ERCP revealed a large filling defect in distal common bile duct. After sphincterotomy, a balloon sweep helped remove a fibrinogenous longitudinal mass with blood clots resolving the obstruction (Figure 2). Histologic examination of aborted cast and the immunoperoxidase studies, which showed strong reaction for hepatocyte specific antigen and were negative to CDX-2, CEA, CK-20, were compatible with hepatocellular carcinoma (HCC). Work up for pre-existing liver disease was negative for viral hepatitis and autoimmune markers. Subsequent hepatic contrast MRI demonstrated a large infiltrative mass replacing the liver and extending into the inferior vena cava and proximal right atrium (Figure 3). HCC is one of the most common cancers in the world. Obstructive jaundice due to HCC is rare. It has been described in approximately 0.5-9% of all cases. This presentation is known as icteric type hepatocellular carcinoma (IHCC). There are several mechanisms for which obstruction can occur in IHCC; tumor compression, hemobilia, migration of the tumor debris or by tumor growth into the bile ducts. IHCC is associated with a poor prognosis, although depends on stage of disease, and the location and extension of tumor thrombi. In view of this rare presentation experts referred to IHCC as a special type of HCC. We report an uncommon case, diagnosed by ERCP, of an abortive HCC presenting as obstructive jaundice. In our case, the use of anticoagulation may have contributed to this unusual presentation.Figure: Axial view, with prominent distention of the common hepatic duct of 1.8 cm x 1.3 cm, with portions of central intra-hepatic duct soft tissue density most compatible with cholangiocarcinoma. There is an area of prominent irregular mass like bulging of the hepatic contour noted hepatic dome measuring approximately 5.2 x 6.9 x 4.4 cm and concerning for peripheral neoplastic mass.Figure: White Fibrinogenous material extracted after balloon sweep and send for analysis.Figure: Axial MRI view showing arge infiltrating hepatic mass extending into the inferior vena cava and proximal right atrium.

Yellow, Yellow, Murky Fellow: A Diagnostic Challenge

2-5% of hospitalized cases with jaundice are caused by drugs; Cephalosporin-induced severe cholestatic injury has been rarely reported. The lack of diagnostic markers and establishing causality makes it a diagnostic challenge. We report a symptomatic case of suspected cephalosporin-induced severe cholestatic injury. 52-year-old male presented with shortness of breath for 3 days. His past medical history was significant for end-stage-renal disease on hemodialysis and cholecystectomy six months back. On physical examination, icterus was noted on the sclera and abdomen along with lower extremity edema. The remainder of the physical examination was unremarkable. On the day of admission: laboratory findings were aspartate transaminase- 61u/L, Alanine transaminase 44u/L, Alkaline phosphatase 611 u/L, total bilirubin 27.5mg/dl and direct bilirubin 25mg/dl. Markers for liver functions including albumin and INR were normal. Subsequent tests for acute viral hepatitis A, B and C, CMV, HSV and EBV were negative. Tests for metabolic liver diseases such as hemochromatosis, Wilsons disease and alpha-1-antitrypsin deficiency were also negative. Autoimmune markers included non-reactive anti-nuclear, anti-mitochondrial, anti-smoothmuscle-antibodies and anti-LKM-antibodies. MRCP was negative for any obstructing residual stone. Liver biopsy showed canalicular cholestasis and ductal proliferation. Importantly, we determined that his LFT's were normal four months back after his laparoscopic cholecystectomy. All drugs taken in the last four months were enumerated that included ceftriaxone and cefdinir. At that time, the initiation of cephalosporins and timing of cholestatic injury served as a clue to our working diagnosis. His RUCAM score was 9 indicating causality as “highly-probable”. Over the course of his stay, his liver function test trended down and was advised to avoid cephalosporins. At follow-up his LFT's did not resolve and was referred to tertiary-care center but he passed away shortly thereafter. Our patient illustrates that DILI should be high in the differential for any patient with unexplained liver function tests with multiple comorbidities. While there is no specific diagnostic test for this disorder, possible toxic drugs can be stopped early in the course along with referral for liver transplant to prevent severe clinical outcome.

Increased Effector Memory Insulin-Specific CD4+ T Cells Correlate With Insulin Autoantibodies in Patients With Recent-Onset Type 1 Diabetes.

Type 1 diabetes (T1D) results from T cell–mediated destruction of insulin-producing β-cells. Insulin represents a key self-antigen in disease pathogenesis, as recent studies identified proinsulin-responding T cells from inflamed pancreatic islets of organ donors with recent-onset T1D. These cells respond to an insulin B-chain (InsB) epitope presented by the HLA-DQ8 molecule associated with high T1D risk. Understanding insulin-specific T-cell frequency and phenotype in peripheral blood is now critical. We constructed fluorescent InsB10–23:DQ8 tetramers, stained peripheral blood lymphocytes directly ex vivo, and show DQ8+ patients with T1D have increased tetramer+ CD4+ T cells compared with HLA-matched control subjects without diabetes. Patients with a shorter disease duration had higher frequencies of insulin-reactive CD4+ T cells, with most of these cells being antigen experienced. We also demonstrate that the number of insulin tetramer+ effector memory cells is directly correlated with insulin antibody titers, suggesting insulin-specific T- and B-cell interactions. Notably, one of four control subjects with tetramer+ cells was a first-degree relative who had insulin-specific cells with an effector memory phenotype, potentially representing an early marker of T-cell autoimmunity. Our results suggest that studying InsB10–23:DQ8 reactive T-cell frequency and phenotype may provide a biomarker of disease activity in patients with T1D and those at risk.

Diagnosis of cobalamin C deficiency with renal abnormality from onset in a Chinese child by next generation sequencing: A case report

The aim of the present study was to present the diagnosis and treatment course of a patient with cobalamin C deficiency (cblC) hospitalized with renal function abnormality from the onset. A female, 7-year-old patient who presented with a cough and progressive dyspnea for 1 day was admitted to the Children's Hospital of Nanjing Medical University (Nanjing, China). A routine clinical examination was performed, including physical examination, routine blood and urine tests, blood gas analysis, computed tomography scans of the head, chest and abdomen, electrocardiogram, echocardiography and abdominal ultrasonography. In addition, laboratory tests were performed, including tests for viral infection and markers of autoimmunity, humoral immunity, myocardial enzymes and tumors. Tandem mass analysis and renal biopsy were conducted. Next generation sequencing (NGS) was performed to identify mutated genes, and structural investigation was conducted to identify the key residue mutations in the patient. Routine clinical examination revealed that the patient had multiple organ failure, indicating the presence of metabolic disease. Tandem mass analysis and renal biopsy also indicated that the patient had methylmalonic acidemia (MMA) and thrombotic microangiopathy combined with focal renal cortical necrosis. Furthermore, next-generation sequencing identified the presence of two heterozygous mutations in the MMA cblC type with homocystinuria (MMACHC) gene. Structural analysis demonstrated that the two mutations were in key components of the MMACHC protein. The patient was finally diagnosed with cblC according to the results obtained. In conclusion, NGS may aid in the diagnosis and therapeutic management of cblC with renal abnormality from the onset in children.

Autoimmune potential of perchloroethylene: Role of lipid-derived aldehydes

Tetrachloroethene (perchloroethylene, PCE), an ubiquitous environmental contaminant, has been implicated in inducing autoimmunity/autoimmune diseases (ADs), including systemic lupus erythematosus (SLE) and scleroderma in humans. However, experimental evidence suggesting the potential of PCE in mediating autoimmunity is lacking. This study was, therefore, undertaken to explore PCE's potential in inducing/exacerbating an autoimmune response. Six-week old female MRL+/+ mice, in groups of 6 each, were treated with PCE (0.5mg/ml) via drinking water for 12, 18 and 24weeks and markers of autoimmunity and oxidative stress were evaluated. PCE exposure led to significant increases in serum anti-nuclear antibodies (ANA), anti-dsDNA and anti-scleroderma-70 (anti-Scl-70) antibodies at 18weeks and, to a greater extent at 24weeks, suggesting that PCE exposure exacerbated autoimmunity in our animal model. The increases in autoantibodies were associated with time-dependent increases in malondialdehyde (MDA)-protein adducts and their antibodies, as well as significantly decreased levels of antioxidants GSH and SOD. The splenocytes isolated from mice treated with PCE for 18 and 24weeks showed greater Th17 cell proliferation and increased release of IL-17 in culture supernatants following stimulation with MDA-mouse serum albumin adducts, suggesting that MDA-modified proteins may act as an immunologic trigger by activating Th17 cells and contribute to PCE-mediated autoimmunity. Our studies thus provide an experimental evidence that PCE induces/exacerbates an autoimmune response and lipid-derived aldehydes (such as MDA) contribute to this response.

Plasma alpha-L-fucosidase activity in chronic inflammation and autoimmune disorders in a pediatric cohort of hospitalized patients.

Human α-fucosidase (EC 3.2.1.51) is an enzyme (hydrolase) of particular biological and medical interest, as the inherited deficiency in its activity leads to fucosidosis, a pathology belonging to severe glycoprotein lysosomal storage disorders. Although its importance has increased in latest years, data about its plasma level in children with inflammatory disorders are still lacking. In the present study, plasma activity of α-L-fucosidase-1 (FUCA-1) and its potential association with chronic inflammatory pathologies was evaluated in hospitalized individuals, both pediatric and adult ones. A number of 201 Hungarian hospitalized patients, 144 children (1-13years) and 57 adults (31-88years), were enrolled in the study and underwent plasma assay of FUCA-1 activity, following the normal routine analytical run in the hospital service. Regression and Pearson tests were evaluated to investigate the relationship between FUCA-1 plasma levels and inflammatory disorders diagnosed with subjects recruited in the study. No correlation of FUCA-1 activity was observed in the pediatric patients with immune (p=0.9677) or metabolic (p=0.6974) disorders, but a correlation was reported when comparing clusters of chronic inflammatory and autoimmune disease vs. controls (p<0.05). Furthermore, a relationship was found between FUCA-1 activity in plasma and inflammatory disorders and autoimmunity both in adults and in the pediatric cohort of patients (Pearson test, p=0.000148). Alterations in plasma levels of FUCA-1 were significantly associated with chronic inflammatory and autoimmune disorders, both in children and adults. The result of the present study should encourage further research on FUCA-1 as a marker of chronic inflammation and autoimmunity.

Clinical implications of antimitochondrial antibody seropositivity in autoimmune hepatitis: a multicentre study

Antimitochondrial antibody (AMA) positivity is the serological marker of primary biliary cholangitis (PBC), but can also be sporadically detected in autoimmune hepatitis (AIH). Little is known about the clinical significance of AMA in AIH. We recruited 47 AMA-positive AIH cases from several centres and compared them with 264 well-characterized Italian AIH patients. Cases with any features of PBC were excluded. In univariate analysis, AMA-positive AIH patients were older (46 vs. 36, P=0.002) and more responsive to immunosuppression (74 vs. 59%, P=0.05), but no differences were observed between the two groups after logistic regression using AMA as a dependent variable. None of the AMA-positive AIH patients showed signs of evolving PBC features after a median follow-up of up 47 months. AMA was detected in combination with all serological AIH markers except antiliver kidney microsome type 1 and antiliver cytosol type 1. AMA was the only marker of autoimmunity in eight cases. We found no differences between AIH with and without AMA. The groups had similar clinical, biochemical and histological features. AMA-positive AIH patients did not evolve towards PBC. In some cases, AMA was the only autoantibody.

Single nucleotide polymorphism 1623 A/G (rs180195) in the promoter of the Thyroglobulin gene is associated with autoimmune thyroid disease but not with thyroid ophthalmopathy.

BackgroundOur studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves’ ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored.MethodsWe identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of TG gene associated with autoimmune thyroid disorders. We genotyped the TG SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls.ResultsWe showed that variant 1623 A/G SNP (rs180195) in the promoter of TG gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto’s thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of TG gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity.Conclusionrs180195 SNP was previously identified by Stefan et al independently of us, who showed that this TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, “Graves’ disease” or “Hashimoto’s disease”, but separate autoimmune disorders.

Definition of the upper reference limit for thyroglobulin antibodies according to the National Academy of Clinical Biochemistry guidelines: comparison of eleven different automated methods

PurposeIn the last two decades, thyroglobulin autoantibodies (TgAb) measurement has progressively switched from marker of thyroid autoimmunity to test associated with thyroglobulin (Tg) to verify the presence or absence of TgAb interference in the follow-up of patients with differentiated thyroid cancer. Of note, TgAb measurement is cumbersome: despite standardization against the International Reference Preparation MRC 65/93, several studies demonstrated high inter-method variability and wide variation in limits of detection and in reference intervals. Taking into account the above considerations, the main aim of the present study was the determination of TgAb upper reference limit (URL), according to the National Academy of Clinical Biochemistry guidelines, through the comparison of eleven commercial automated immunoassay platforms.MethodsThe sera of 120 healthy males, selected from a population survey in the province of Verona, Italy, were tested for TgAb concentration using eleven IMA applied on as many automated analyzers: AIA-2000 (AIA) and AIA-CL2400 (CL2), Tosoh Bioscience; Architect (ARC), Abbott Diagnostics; Advia Centaur XP (CEN) and Immulite 2000 XPi (IMM), Siemens Healthineers; Cobas 6000 (COB), Roche Diagnostics; Kryptor (KRY), Thermo Fisher Scientific BRAHMS, Liaison XL (LIA), Diasorin; Lumipulse G (LUM), Fujirebio; Maglumi 2000 Plus (MAG), Snibe and Phadia 250 (PHA), Phadia AB, Thermo Fisher Scientific. All assays were performed according to manufacturers’ instructions in six different laboratories in Friuli-Venezia Giulia and Veneto regions of Italy [Lab 1 (AIA), Lab 2 (CL2), Lab 3 (ARC, COB and LUM), Lab 4 (CEN, IMM, KRY and MAG), Lab 5 (LIA) and Lab 6 (PHA)]. Since TgAb values were not normally distributed, the experimental URL (e-URL) was established at 97.5 percentile according to the non-parametric method.ResultsTgAb e-URLs showed a significant inter-method variability. Considering the same method, e-URL was much lower than that suggested by manufacturers (m-URL), except for ARC and MAG. Correlation and linear regression were unsatisfactory. Consequently, the agreement between methods was poor, with significant bias in Bland–Altman plot.ConclusionsDespite the efforts for harmonization, TgAb methods cannot be used interchangeably. Therefore, additional effort is required to improve analytical performance taking into consideration approved protocols and guidelines. Moreover, TgAb URL should be used with caution in the management of differentiated thyroid carcinoma patients since the presence and/or the degree of TgAb interference in Tg measurement has not yet been well defined.

Early childhood infections precede development of beta-cell autoimmunity and type 1 diabetes in children with HLA-conferred disease risk.

The etiology of type 1 diabetes (T1D) is largely unknown. Infections and microbial exposures are believed to play a role in the pathogenesis and in the development of islet autoimmunity in genetically susceptible individuals. To assess the relationships between early childhood infections, islet autoimmunity, and progression to T1D in genetically predisposed children. Children with human leukocyte antigen (HLA)-conferred disease susceptibility (N=790; 51.5% males) from Finland (n = 386), Estonia (n = 322), and Russian Karelia (n = 82) were observed from birth up to the age of 3 years. Children attended clinical visits at the age of 3, 6, 12, 18, 24, and 36 months. Serum samples for analyzing T1D-associated autoimmune markers were collected and health data recorded during the visits. Children developing islet autoimmunity (n = 46, 5.8%) had more infections during the first year of life (3.0 vs 3.0, mean rank 439.1 vs 336.2; P = .001) and their first infection occurred earlier (3.6 vs 5.0 months; P = .005) than children with no islet autoimmunity. By May 2016, 7 children (0.9%) had developed T1D (progressors). Compared with non-diabetic children, T1D progressors were younger at first infection (2.2 vs 4.9 months; P = .004) and had more infections during the first 2 years of life (during each year 6.0 vs 3.0; P = .001 and P = .027, respectively). By 3 years of age, the T1D progressors had twice as many infections as the other children (17.5 vs 9.0; P = .006). Early childhood infections may play an important role in the pathogenesis of T1D. Current findings may reflect either differences in microbial exposures or early immunological aberrations making diabetes-prone children more susceptible to infections.

Late-onset Rasmussen Encephalitis: A literature appraisal.

Rasmussen Encephalitis (RE) is classically described as a childhood encephalopathy due to a unilateral inflammation of the cerebral cortex with a presumed immune-mediated pathophysiological basis. Unusual variant forms, including adolescent and adult-onset RE have been described but there is still a doubt whether these atypical cases correspond to classical RE patients. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing late onset RE to assess (i) the positivity rate of classical childhood-onset diagnostic criteria for RE in late-onset RE, (ii) the specific clinical and radiological features that could help earlier diagnosis and therapeutic interventions, (iii) the arguments for an autoimmune pathophysiology including (iiia) the association with autoimmune markers or diseases and (iiib) the effects of immunomodulatory or immunosuppressive treatments. A total of 50 papers were considered. We identified 102 late-onset RE patients with a sex ratio of 8 women for 2 men. 67% fulfilled the consensus diagnostic criteria for RE. As compared to classical RE, the late-onset RE patients exhibited: i) more frequent focal complex partial seizures, ii) less frequent epilepsia partialis continua throughout evolution, iii) a slower evolution with a delayed occurrence of cortical deficit, iv) less cognitive deterioration and v) a better outcome. A specific association with autoimmune markers or diseases was not found. Immunomodulatory therapies, even performed in a late stage, improved late-onset RE patients in 61% of cases. This review proves that late-onset RE is a reality with specific clinical and radiological features. The good response to immunomodulatory treatments brings further arguments for an immune-regulated process.

Treatment and retreatment with omalizumab in chronic spontaneous urticaria: Real life experience with twenty-five patients

BackgroundPrevious data have shown the high efficacy of omalizumab in chronic spontaneous urticaria (CSU). However, factors that may be effective on the response to therapy, relapse rates after drug discontinuation, and efficacy of retreatment remain unclear. This study aimed to determine the efficacy of omalizumab in CSU refractory to conventional therapy, to identify possible factors affecting treatment response and relapse, and also to evaluate the efficacy of retreatment on relapsed disease. MethodsThe data of CSU patients treated with 300 mg/month omalizumab for at least 3 months were retrospectively analyzed. In order to evaluate the efficacy of treatment and retreatment, baseline and follow-up concomitant medication score (CMS) and urticaria activity score (UAS) were calculated. Possible factors affecting treatment response and relapse were identified. ResultsTwenty-five patients were included. The median duration of omalizumab therapy was 6 (6–12) months. Of the patients with baseline UAS 6 (5.5–6) and CMS 13 (10–15), 8 (32%) had complete response (UAS = 0) and 2 (8%) were non-responders after 3 months of therapy. None of the complete responders were positive for IgG-anti-TPO. After discontinuation of omalizumab therapy, 11 (61%) patients experienced relapse and 10 of them received retreatment with omalizumab. Half of the patients had complete response, and half had partial response (UAS = 1–4) after retreatment. No treatment related adverse events were documented. ConclusionsOmalizumab has high efficacy in both the treatment and retreatment of CSU; however, relapse rates after discontinuation are high. Autoimmune markers may be helpful in predicting treatment response and relapse.