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Autoantibodies - Top 30 Publications

Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease.

Recent reports suggest an involvement of Th17 responses in inflammatory and autoimmune reactions in alcoholic liver disease (ALD). Our study aimed to assess serum levels of Th17-interleukins in ALD with regard to the frequency of liver-specific autoantibodies and degree of liver damage.

Undifferentiated connective tissue diseases and adverse pregnancy outcomes. An undervalued association?

Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well-known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.

Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?

Interstitial pneumonia with autoimmune features (IPAF) identifies a recently recognized autoimmune syndrome characterized by interstitial lung disease and autoantibodies positivity, but absence of a specific connective tissue disease diagnosis or alternative etiology. We retrospectively reviewed the clinical presentation, diagnostic workup and management of seven critically ill patients who met diagnostic criteria for IPAF. We compared baseline characteristics and clinical outcome of IPAF patients with those of the population of ARDS patients admitted in the same period.

Antibodies against citrullinated alpha enolase peptides in primary Sjogren's syndrome.

Citrullinated alpha enolase (CEP-1) has been designated as a major antigenic target of antibodies against citrullinated proteins (ACPA) in patients with rheumatoid arthritis (RA). Our aim is to determine the prevalence of anti-CEP-1 in a cohort of ACPA positive (ACPA+) primary Sjogren's syndrome (pSS) patients. Anti-CEP1 titers were determined by ELISA in sera from 15 ACPA+ and 45 ACPA- age/sex matched pSS; 12 ACPA+ RA patients and 30 healthy controls (HC). Increased anti-CEP-1 antibody titers were detected in nine out of the 15 (60%) ACPA+ pSS patients and 5 out of 12 (41.7%) ACPA+ RA patients; no reactivities were detected in ACPA- pSS patients and HC. Anti-CEP-1 antibodies in the setting of pSS were associated with higher urine pH levels at baseline. CEP-1 is a major antigenic target of ACPA in patients with pSS characterizing a subgroup with distinct laboratory features.

Depressed serum IgM levels in SLE are restricted to defined subgroups.

Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM anti-phosphorylcholine (PC) antigens and anti-malondialdehyde (MDA) modified-protein, as well total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/β2glycoprotein-I. We also observed an association of reduced IgM levels with the HLA-DRB1*03 allelic variant among SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM, and suggest that low IgM levels in a SLE patient may reflect underlying immunological differences.

Immunoadsorption in neurological disorders.

In recent years, immunoadsorption has been increasingly recognized as an alternative to therapeutic plasma exchange and used for the treatment of neurological disorders such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, neuromyelitis optica spectrum disorders, and multiple sclerosis, as well as autoimmune encephalitis. Unlike therapeutic plasma exchange, which requires fluid replacement with a blood solution such as fresh frozen plasma or albumin, immunoadsorption is a blood purification technique that enables the selective removal of humoral factors from separated plasma through a high-affinity adsorbent with tryptophan or phenylalanine. Although the mechanisms underlying the therapeutic effects of immunoadsorption treatment remain to be fully elucidated, they are based on the removal of pathogenic humoral factors from circulating blood, such as disease-specific autoantibodies, complement, and inflammatory cytokines. The American Society for Apheresis has published evidence-based guidelines on the use of therapeutic apheresis in clinical practice, with specific instructions on 16 neurological disorders. However, the modality recommended in the guidelines for most of these disorders is therapeutic plasma exchange. This part of our review focuses on the clinical aspects of immunoadsorption. We also describe the efficacy of immunoadsorption and the evidence obtained by previous studies of the treatment of neurological disorders. Immunoadsorption could greatly improve the treatment of patients with autoimmune neurological disorders but further evidence is needed to confirm the efficacy of immunoadsorption in clinical practice.

Insulin autoimmune syndrome (Hirata's disease) in an Italian patient: a case report and review of the literature.

We describe the case of a 54-year-old Caucasian Italian male experiencing episodes of hypoglycemia, occurring mainly after meals. He had never been exposed to insulin and was taking ramipril, flecainide and acetylsalicylic acid. An oral glucose tolerance test (OGTT) showed high blood glucose levels diagnostic for diabetes mellitus at 120 min and hypoglycemia with inappropriately high insulin levels at 240 min. The 72-h fasting test, abdominal computed tomography (CT) and positron emission tomography-CT were normal. Insulin autoantibodies were positive at high titers, prompting a diagnosis of insulin autoimmune syndrome (IAS). The patient was advised to take frequent, small meals and thus achieved a good control of his hypoglycemic symptoms. After 18 months of this dietary management, his insulin autoantibody levels decreased considerably but remained detectable. During an OGTT, his blood glucose levels at 120 min were now indicative of an impaired glucose tolerance rather than diabetes, and there was improvement in the glucose nadir. The patient had no other clinical or latent autoimmune diseases. Here we discuss the main features of IAS (also known as Hirata's disease) and review the cases of IAS reported in Italy to date.

A case of severe acquired hypertriglyceridemia in a 7-year-old girl.

We report a case of severe type I hyperlipoproteinemia caused by autoimmunity against lipoprotein lipase (LPL) in the context of presymptomatic Sjögren's syndrome. A 7-year-old mixed race (Caucasian/African American) girl was admitted to the intensive care unit at Vanderbilt Children's Hospital with acute pancreatitis and shock. She was previously healthy aside from asthma and history of Hashimoto's thyroiditis. Admission triglycerides (TGs) were 2191 mg/dL but returned to normal during the hospital stay and in the absence of food intake. At discharge, she was placed on a low-fat, low-sugar diet. She did not respond to fibrates, prescription fish oil, metformin, or orlistat, and during the following 2 years, she was hospitalized several times with recurrent pancreatitis. Except for a heterozygous mutation in the promoter region of LPL, predicted to have no clinical significance, she had no further mutations in genes known to affect TG metabolism and to cause inherited type I hyperlipoproteinemia, such as APOA5, APOC2, GPIHBP1, or LMF1. When her TG levels normalized after incidental use of prednisone, an autoimmune mechanism was suspected. Immunoblot analyses showed the presence of autoantibodies to LPL in the patient's plasma. Autoantibodies to LPL decreased by 37% while patient was on prednisone, and by 68% as she subsequently transitioned to hydroxychloroquine monotherapy. While on hydroxychloroquine, she underwent a supervised high-fat meal challenge and showed normal ability to metabolize TG. For the past 3 years and 6 months, she has had TG consistently <250 mg/dL, and no symptoms of, or readmissions for, pancreatitis.

Interactions of antisera to different Chlamydia and Chlamydophila species with the ribosomal protein RPS27a correlate with impaired protein synthesis in a human choroid plexus papilloma cell line.

Chlamydia trachomatis (CT) and the Chlamydophila species (CS) Chlamydophila pneumoniae (CPn), and Chlamydophila psittaci (CPs) are suggested to induce autoantibodies causative of several human autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus (SLE). The aim of the present study was therefore to identify cellular protein interaction partners with antisera to CT (α-CT) or CS (α-CS) and to identify functional consequences of such interaction in vitro. As detected with a commercial first trimester human prenatal brain multiprotein array (hEXselect, Engine, Germany), the most frequent interaction partner with both α-CT and α-CS was the ribosomal small subunit protein RPS27a. This could be confirmed by Western blot analysis with a recombinant RPS27a sample. In addition, immunocytochemistry with both antisera in the human choroid plexus papilloma cell line HIBCPP revealed a granular cytoplasmic staining, and Western blot analysis with whole-cell protein samples of HIBCPP cells revealed both antisera to label protein bands of different molecular weights and intensity. By 2D Western blot analysis and mass spectrometry, one of the protein spots interacting with α-CT could be identified as the RPS27a. Finally, two different methods for the detection of protein synthesis activity, the SUnSET technique and an HPG fluorescence assay revealed both antisera to cause reduced translational activity in HIBCPP cells. Together with previous findings of RPS27a as an autoimmune target in a mouse model of systemic lupus erythematosus (SLE), these results suggest that infections with CT and/or CS could induce SLE-associated immune modifications. However, direct evidence for a pathogenic role of these interactions for SLE demands further investigations.

A novel mutation in the hepatocyte nuclear factor-1β gene in maturity onset diabetes of the young 5 with multiple renal cysts and pancreas hypogenesis: A case report.

A 17-year-old Chinese male was hospitalized exhibiting hyperglycemia and increased serum urea nitrogen and creatinine levels in addition to weight loss. The patient was treated with gliclazide. The patient was 150 cm tall, weighed 35 kg and had no family history of diabetes or kidney disease. Physical examination revealed cephalus quadratus, rachitic rosary and a visible toe-out gait. Laboratory examinations revealed that the patient's fasting plasma glucose and glycosylated hemoglobin levels were markedly increased, fasting plasma C-peptide level was slightly increased and no peak 2 h postprandial was observed. Diabetic autoimmune antibodies [islet cell cytoplasmic autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), isulinoma-2-associated autoantibodies (IA2A) and insulin autoantibodies (IAA)] were negative. Levels of serum electrolytes decreased, uric acid and parathyroid hormone increased, mild albuminuria was detected and there was a low proportion of urine. The patient also presented with low bone mass and cataracts. Abdominal computed tomography (CT) revealed a bilateral atrophic kidney with multiple renal cysts, primarily located at the junction of renal cortex and medulla, with a diameter of 0.3-0.7 cm. CT also revealed hypogenesis of the body and tail of the pancreas. In an oral glucose tolerance test, the mother and paternal uncle of the patient were diagnosed with type II diabetes and the patient's sister, maternal uncle and paternal grandpa were diagnosed with glucose tolerance impairment. Genetic testing revealed an unreported amino acid mutation in exon 2 of hepatocyte nuclear factor 1β (c.391C>T), a nonsense mutation of CAA to TAA at codon 131. This mutation was identified in the proband but not in any other family members.

Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.

Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials.

Indoleamine 2,3-dioxygenase 1, Increased in Human Gastric Pre-Neoplasia, Promotes Inflammation and Metaplasia in Mice and is Associated with Type II Hypersensitivity/Autoimmunity.

Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia.

Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1.

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare.

Parity and Risk of Thyroid Autoimmunity Based on the NHANES (2001-2002, 2007-2008, 2009-2010, and 2011-2012).

Autoimmune thyroid disease is more common in women than in men. Fetal microchimerism has been implicated as a potential explanation for this disparity.

The role of the B lymphocytes in endometriosis: A systematic review.

The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for "endometriosis", "B cells" and "B lymphocytes" in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells.

Differential antibody glycosylation in autoimmunity: sweet biomarker or modulator of disease activity?

A loss of humoral tolerance is a hallmark of many autoimmune diseases and the detection of self-reactive antibodies (autoantibodies) of the immunoglobulin G (IgG) isotype is widely used as a biomarker and diagnostic tool. However, autoantibodies might also be present in individuals without autoimmune disease, thus limiting their usefulness as a sole indicator of disease development. Moreover, while clear evidence exists of the pathogenic effects of autoantibodies in mouse model systems, the contribution of autoantibodies to the pathology of many autoimmune diseases has yet to be established. In this Review, the authors discuss the changes in total serum IgG and autoantibody glycosylation that occur during autoimmune disease and how these changes might help to predict disease development in the future. Furthermore, current knowledge of the signals regulating antibody glycosylation and how individual antibody glycoforms could be used to optimize current treatment approaches will be discussed.

Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti-TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell-based assay. Anti-TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small-cell lung carcinoma.

Pediatric Autoimmune Encephalitis.

Autoimmune (antibody mediated) encephalitis (AE) is emerging as a more common cause of pediatric encephalopathy than previously thought. The autoimmune process may be triggered by an infection, vaccine, or occult neoplasm. In the latter case, onconeural autoantibodies are directed against intracellular neuronal antigens, but a recent heterogeneous group of encephalitic syndromes has been found not to have underlying tumor but is associated with autoantibodies to the neuronal surface or synaptic antigens. Neuropsychiatric symptoms are very common in autoimmune encephalopathy; as a result, affected children may be initially present to psychiatrists. Neurological features are movement disorders, seizures, altered conscious level, and cognitive regression. Hypoventilation and autonomic features may be an aspect. Inflammatory findings in the cerebrospinal fluid may be present but are relatively nonspecific. Magnetic resonance imaging (MRI) may also demonstrate abnormalities that provide clues for diagnosis, particularly on fluid-attenuated inversion recovery or T2-weighted images. AE is well responsive to immune therapy, with prompt diagnosis and treatment strongly beneficial. Patients with paraneoplastic encephalitis are more refractory to treatment compared to those in whom no malignancy is identified. Herein, the authors present an update of literature data on the clinical presentation, laboratory and imaging findings, therapy, and outcomes for the most common autoimmune encephalitides.

Utility of Determining Autoantibodies to M-type Phospholipase A2 Receptor in Diagnosing Primary Membranous Nephropathy: An Ideal Setting.

The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History to the Progression from Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report.

This paper seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to T1D risk among autoantibody positive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, INS gene (rs1004446_A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium. The risk of progression to T1D was not different among those with or without a family history of T1D (p=0.39) nor HLA-DR-DQ genotypes (p=0.74). Age at developing multiple autoantibodies (HR=0.96 per 1 month increase in age, 95% CI=0.95, 0.97, p<0.001) and the type of first autoantibody (when more than a single autoantibody was the first appearing indication of seroconversion [p=0.006]) were statistically significant. Female sex was also a significant risk factor (p=0.03). Three SNPs were associated with increased diabetes risk (rs10517086_A, [p=0.03], rs1534422_G, [p=0.006], and rs2327832_G in TNFAIP3 [p=0.03]), and one with decreased risk (rs1004446_A in INS, [p=0.006]). The TEDDY data suggest that non-HLA gene polymorphisms may play a different role in the initiation of autoimmunity than they do in progression to T1D once autoimmunity has appeared. The strength of these associations may be related to the age of the population and the high-risk HLA-DR-DQ subtypes studied.

Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases: an updated review.

Polycystic ovary syndrome (PCOS) is defined by hyperandrogenism, irregular menses and polycystic ovaries when other causes are excluded. The possible implication of increased morbidity in PCOS for screening and follow-up is uncertain and is reviewed in this article.

The Role of Monocyte Percentage in Osteoporosis in Male Rheumatic Diseases.

Osteoporosis is easily overlooked in male patients, especially in the field of rheumatic diseases mostly prevalent with female patients, and its link to pathogenesis is still lacking. Attenuated monocyte apoptosis from a transcriptome-wide expression study illustrates the role of monocytes in osteoporosis. This study tested the hypothesis that the monocyte percentage among leukocytes could be a biomarker of osteoporosis in rheumatic diseases. Eighty-seven males with rheumatic diseases were evaluated in rheumatology outpatient clinics for bone mineral density (BMD) and surrogate markers, such as routine peripheral blood parameters and autoantibodies. From the total number of 87 patients included in this study, only 15 met the criteria for diagnosis of osteoporosis. Both age and monocyte percentage remained independently associated with the presence of osteoporosis. Steroid dose (equivalent prednisolone dose) was negatively associated with BMD of the hip area and platelet counts were negatively associated with BMD and T score of the spine area. Besides age, monocyte percentage meets the major requirements for osteoporosis in male rheumatic diseases. A higher monocyte percentage in male rheumatic disease patients, aged over 50 years in this study, and BMD study should be considered in order to reduce the risk of osteoporosis-related fractures.

Brainstem encephalitis and acute polyneuropathy associated with hepatitis E infection.

A 59-year-old man presented with feverish illness. His Glasgow Coma Scale was 15, had reduced visual acuity in the left eye with partial left ptosis and mild left hemiparesis with an extensor left plantar. Over 48 hours, he accrued multiple cranial nerves palsies and progressed to a flaccid paralysis necessitating admission to an intensive care unit.Cerebrospinal fluid (CSF) study showed 20 lymphocytes and raised protein. Viral and bacterial PCRs were negative. Samples for Lyme, blood-borne viruses, syphilis and autoantibodies were also negative. MRI brain showed T2 abnormalities within the brainstem. Nerve conduction studies revealed an acute motor and sensory axonal neuropathy pattern of Guillian Barre Syndrome (GBS). The patient was treated for both infective and inflammatory causes of brainstem encephalitis and GBS.Retrospective studies confirmed the presence of hepatitis E virus (HEV) RNA in CSF and serum studies showed positive HEV IgG and IgM prior to intravenous infusion. After 3 months of intensive rehabilitation, the patient was discharged home walking with a frame.

B cell-derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity.

Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell-derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell-derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell-intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation.

Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons.

Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA.

The anti-C1s antibody TNT003 prevents complement activation in the skin induced by bullous pemphigoid autoantibodies.

The deposition of anti-DNA IgG contributes to the development of cutaneous lupus erythematosus.

Anti-DNA IgG is a hallmark of systemic lupus erythematosus and induces internal injuries in patients. It is known that cutaneous lupus erythematosus (CLE) involves the deposition of autoantibodies in the dermoepidermal junction of the skin and that anti-DNA IgG binds specifically to keratinocytes. However, the definite role of anti-DNA IgG in CLE remains unclear. The purpose of this study was to elucidate the effect of anti-DNA IgG on keratinocytes in CLE. Skin tissues were collected from patients with CLE and healthy controls. Also, murine anti-DNA IgG was incubated with frozen sections of murine skin or PAM212 keratinocytes. The chemotaxis of J774.2 macrophages was evaluated in special chambers with keratinocytes under anti-DNA IgG stimulation. Enzyme-linked immunosorbent assay, flow cytometry, Western blot, and surface plasmon resonance were used to quantitate the interaction between anti-DNA IgG and keratinocyte-related self-antigens. The results showed that anti-DNA IgG could be eluted from the lesional tissues of CLE patients, depending on the serum positivity. Murine anti-DNA IgG bound preferably to the dermoepidermal zones of normal skin and specifically to collagen III and the suppressor of cytokine signalling 1 (SOCS1) but not to Ro52. Moreover, the chemotaxis of macrophages was promoted by the incubation of anti-DNA IgG with keratinocytes. Interestingly, anti-DNA IgG exaggerated both the expression and the activation of fibroblast growth factor inducible 14 (Fn14) in keratinocytes and regulated SOCS1 signals in a time-dependent manner. In conclusion, anti-DNA IgG may contribute to the development of CLE through binding to keratinocyte-related antigens, exacerbating inflammatory infiltration, and modulating Fn14 and SOCS1 pathways.

A role for autoantibodies in atherogenesis.

An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the association between autoantibodies and atherosclerosis, amongst individuals without clinical autoimmune disease. An electronic search of five databases to June 2016 was performed by two independent reviewers. Inclusion criteria were analytical studies of adults, with at least two studies per autoantibody. Quality analysis was carried out using the Newcastle-Ottawa scale and the Cochrane Risk of Bias Quality Assessment Tool where appropriate. Where possible, studies were pooled using random effects models. Raised levels of anti-cardiolipin (odds ratio [OR] = 1.30; 95% CI: 1.15-1.49) and anti-oxidized low-density lipoprotein Immunoglobulin (Ig) G (OR = 1.25; 95% CI: 1.11-1.41), unspecified anti-cyclic citrullinated protein (OR = 3.09; 95% CI: 1.49-6.41) and anti-human heat shock protein 60 IgA (OR = 1.57; 95% CI: 1.15-2.16) were observed to increase the risk of cardiovascular outcomes. Alternatively, Anti-phosphorylcholine IgM (OR = 1.31; 95% CI: 1.14-1.50) conferred protection against CVD. Our results support an important role for autoantibodies in mediating cardiovascular events, independent of therapeutic treatments. Future research may focus on the presence of autoantibodies as markers of immune dysregulation and CVD risk.

"Autoimmune(-Like)" Drug and Herb Induced Liver Injury: New Insights into Molecular Pathogenesis.

Idiosyncratic drug-induced liver injury (DILI) and hepatic injury due to herbal and dietary supplements (HDS) can adapt clinical characteristics of autoimmune hepatitis (AIH), such as the appearance of autoantibodies and infiltration of the liver by immune competent cells. To describe these cases of DILI/HDS, the poorly-defined term "autoimmune(-like)" DILI/HDS came up. It is uncertain if these cases represent a subgroup of DILI/HDS with distinct pathomechanistic and prognostic features different from "classical" DILI/HDS. Besides, due to the overlap of clinical characteristics of "immune-mediated" DILI/HDS and AIH, both entities are not easy to differentiate. However, the demarcation is important, especially with regard to treatment: AIH requires long-term, mostly lifelong immunosuppression, whereas DILI/HDS does not. Only through exact diagnostic evaluation, exclusion of differential diagnoses and prolonged follow-up can the correct diagnosis reliably be made. Molecular mechanisms have not been analysed for the subgroup of "autoimmune(-like)" DILI/HDS yet. However, several pathogenetic checkpoints of DILI/HDS in general and AIH are shared. An analysis of these shared mechanisms might hint at relevant molecular processes of "autoimmune(-like)" DILI/HDS.

Autoimmune Hepatitis - Primary Biliary Cirrhosis Overlap Syndrome.

Autoimmune Hepatitis (AIH) and Primary Biliary Cirrhosis (PBC) are important immune mediated liver diseases. They are usually differentiated based on clinical, biochemical, serological and histological parameters. The presence of autoantibodies, clinical and serological findings can sometimes occur in different combinations leading to overlap syndromes, which is rare. Early recognition of such overlap syndromes is clinically significant from treatment point of view. Here, we report a case of AIH-PBC overlap syndrome with a brief review of literature on overlap syndromes.