Presence Of Several Autoantibodies Research Articles

COVID-19 infection: a possible induction factor for development of autoimmune diseases?

Following the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the importance of investigation of the pathogenesis and immunological characteristics of COVID-19 became quite clear. Currently, there are reports indicating that COVID-19 is able to induce autoimmune responses. Abnormal immune reactions are a cornerstone in the pathogenicity of both conditions. Detection of autoantibodies in COVID-19 patients may suggest a link between COVID-19 and autoimmunity. In this study, we focused on the similarities and possible differences between COVID-19 and autoimmune disorders to explore the relationship between them. Comparing the pathogenicity of SARS-CoV-2 infection with autoimmune conditions revealed significant immunological properties of COVID-19 including the presence of several autoantibodies, autoimmunity-related cytokines, and cellular activities that could be useful in future clinical studies aiming at managing this pandemic.

The chemokine landscape: one system multiple shades.

Leukocyte trafficking is mainly governed by chemokines, chemotactic cytokines, which can be concomitantly produced in tissues during homeostatic conditions or inflammation. After the discovery and characterization of the individual chemokines, we and others have shown that they present additional properties. The first discoveries demonstrated that some chemokines act as natural antagonists on chemokine receptors, and prevent infiltration of leukocyte subsets in tissues. Later on it was shown that they can exert a repulsive effect on selective cell types, or synergize with other chemokines and inflammatory mediators to enhance chemokine receptors activities. The relevance of the fine-tuning modulation has been demonstrated invivo in a multitude of processes, spanning from chronic inflammation to tissue regeneration, while its role in the tumor microenvironment needs further investigation. Moreover, naturally occurring autoantibodies targeting chemokines were found in tumors and autoimmune diseases. More recently in SARS-CoV-2 infection, the presence of several autoantibodies neutralizing chemokine activities distinguished disease severity, and they were shown to be beneficial, protecting from long-term sequelae. Here, we review the additional properties of chemokines that influence cell recruitment and activities. We believe these features need to be taken into account when designing novel therapeutic strategies targeting immunological disorders.

Influence of reproductively significant autoantibodies on the quality of oocytes, obtained embryos and the chances of implantation in Assisted Reproductive Technologies cycles. Literature review

There is evidence suggesting that autoimmune mechanisms may influence fertility, manifesting as infertility or pregnancy loss. Numerous autoimmune diseases, including but not limited to systemic lupus erythematosus, anti-phospholipid syndrome and Hashimoto thyroiditis may be associated with infertility and pregnancy loss through different putative mechanisms. It is notable that fertility may be impaired in the presence of serum autoantibodies regardless of the presence of a clinically overt autoimmune disease. Autoimmunity may affect all stages of fertility via ovarian failure, implantation failure, and pregnancy loss. This review article will illustrate and discuss the available data on the link between chances of achieving pregnancy through Assisted Reproductive Technologies in real clinical setting in the presence of several autoantibodies affecting female reproductive system. Summarizing the available data from the world literature, it can be concluded that necessity exist in development of a reproductively significant antibodies line in application to direct, cross-over and cumulative assessment of the role of autoimmune antibodies carriage in the implementation of reproductive failures,bearing in mind new approaches to the strategy of overcoming autoimmune reproductive failure.

Imbalance of peripheral follicular helper T lymphocyte subsets in active vitiligo.

Vitiligo is an autoimmune disease characterized by the presence of several autoantibodies, some of which are directed against melanocyte components and have been shown to be associated with the progression of the disease. However, the mechanism involved in the production of autoantibodies remains unclear. Follicular helper CD4+ T cells (TFH) are specialized in B-cell activation and antibody production, especially the TFH cell subsets type 2 and type 17. To date, TFH cell subsets have not been studied in human vitiligo. This study in 44 vitiligo patients and 19 healthy controls showed an increase in circulating TFH cells associated with disease clinical progression. A more precise analysis of TFH cell phenotype demonstrated that vitiligo is characterized by populations of peripheral TFH cells responsible for helping B-cell function, such as TFH type 2 and type 17 which produce Th2- and TH17-related cytokines, respectively. These findings suggest a new mechanism involving TFH cell subsets in the pathogenesis of human vitiligo and leading to the production of autoantibodies and disease.

A1.29 In rheumatoid arthritis, smoking is not primarily associated with anti-citrullinaged protein antibodies, but with the presence of several autoantibodies

Background and ObjectivesIn rheumatoid arthritis (RA), smoking has been described to be specifically associated with the presence of anti-citrullinated protein antibodies (ACPA). However, smoking has also been shown to be...

Neuropsychiatric systemic lupus erythematosus: pathophysiology and the future of treatment

Systemic lupus erythematosus (SLE) is characterized by the presence of several autoantibodies, including anti-dsDNA. Among types of SLE, neuropsychiatric (NP)-SLE accounts for significant morbidity and mortality. Cerebrovascular disease, which could account for most of the serious permanent neurological damage, is a common presentation of NP-SLE. The pathophysiology of NP-SLE involves several factors, including vasculitis, thrombosis, and inflammation and/or apoptosis of neuronal and glial cells. The current treatment strategy is immunosuppressive therapy, which is occasionally insufficient for patients with NP-SLE. Recent studies have revealed that autoantibodies, such as anti-NR2, pass from the peripheral blood to the brain through the blood–brain barrier, cross-react with human brain tissue and cause increased intracellular Ca2+ in SLE. Regulating blood–brain barrier permeability, inhibiting autoantibody deposition in tissues and modulating intracellular Ca2+ may be new concepts for the treatment with ...

Advances in the pathogenesis and treatment of primary Sj(o)gren's syndrome

Sj(o)gren's syndrome(SS)is a chronic autoimmune inflammatory disease characterized by predominant infiltration of lymphocytes in exocrine glands as well as presence of several autoantibodies in sera.Primary SS(pSS)is the condition in the absence of other definitively diagnosed autoimmune diseases.The pathogenesis of pSS remains unclear.Currently,pSS is considered to be induced by multiple environmental factors and endogenous antigens,which trigger a self-perpetuating inflammatory response in susceptible individuals,lead to abnormal cellular and humoral immunity followed by the impairment of exocrine glands,production of autoantibodies and damage to target organs.Although no ideal therapy is available,biological agents have offered new clues to the treatment of pSS. Key words: Sj(o)gren's syndrome; Diagnosis; Therapy

SAT0217 Anti- RO/SSA Antibodies in Systemic Sclerosis: Frequency and Clinical Associations in a Monocentric Referral Cohort

BackgroundSystemic Sclerosis (SSc) is an autoimmune connective tissue disease (CTD) characterized by the presence of several autoantibodies that correlate with diagnostic and prognostic aspects of the disease. Besides those autoantibodies...

Discoveries in the pathophysiology of neuropsychiatric lupus erythematosus: consequences for therapy

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disorder characterized by the presence of several autoantibodies, including anti-double-stranded DNA. Neuropsychiatric (NP)LE contributes to the prognosis of SLE, and is divided into 19 NPLE syndromes. Its mechanisms are mediated through autoantibodies, complement components, and cytokines. The pathophysiology and diagnosis of NPLE are diverse and complicated. Recent studies have shown that several autoantibodies cross-react with human brain tissue and cause NPLE symptoms in SLE. It is known that in mice, depression and hippocampus-related memory impairment are induced by anti-ribosomal P antibody and anti-NR2 antibody, respectively. In a BMC Medicine research article, Kivity et al. demonstrated novel work showed that the 16/6 Id antibody impaired visual memory and spatial memory by causing hippocampal injury in mice. Given differences in the cross-reactivity of each autoantibody with the nervous system, the clinical features might be different and diverse in NPLE. Identification of autoantibody targets could lead to the development of novel therapies. Investigators and clinicians should consider not only the inhibition of autoantibody synthesis but also the protection of neuronal cells in the treatment strategy for NPLE.See related Research article: http://www.biomedcentral.com/1741-7015/11/90

Clinical and Radiographic Heterogeneity of Interstitial Lung Disease in Systemic Sclerosis Based on Disease-Specific Autoantibodies

Patients with SSc have the presence of several autoantibodies, some of which are SSc-specific antibodies associated with the clinical features of SSc (9-13). The presence of anti-topoisomerase I (topo-I) antibody is associated with the development of skin fibrosis and progressive ILD in SSc. Anti-centromere antibody (ACA) is seen in patients with limited skin disease and is a minor risk factor for the development of ILD. However, it remains unclear whether SSc-specific antibodies are associated with pulmonary function and radiological findings of HRCT. We divided SSc patients into 5 clusters on the basis of SSc-specific autoantibodies present and retrospectively evaluated the clinical and radiological features of ILD among these 5 SSc patient clusters. Abstract Background: Patients with systemic sclerosis have the presence of several autoantibodies, some of which are systemic sclerosis-specific autoantibodies that are related to the clinical features of this disease. We retrospectively evaluated the clinical and radiological features of systemic sclerosis in patients with interstitial lung disease on the basis of these autoantibodies. Method: This study comprised 226 patients with systemic sclerosis. We divided patients with systemic sclerosis into 5 clusters based on the systemic sclerosis-specific autoantibodies present and compared the clinical and radiological features of interstitial lung disease among these 5 systemic sclerosis clusters. Results: Of 226 patients, interstitial lung disease was present in 73 (32.3%) patients. Clustering by Ward cluster analysis subsequently identified 5 major clusters of patients. Clusters of patients with anti-topoisomerase I antibody and without systemic sclerosis-specific autoantibodies had a higher incidence of interstitial lung disease compared to the other clusters (75.0% and 51.9%, respectively). Patients in these two clusters had higher percentages of cough and dyspnea, higher incidence of traction bronchiectasis and honeycomb-like cysts in computed tomography, and a decrease in percentage predicted of vital capacity. In contrast, patients with anti-centromere antibody had few clinical and laboratory findings and the lowest incidence of interstitial lung disease (16.8%). Patients with anti- ribonucleic antibody or nucleolar pattern in anti-nuclear antibody had moderate findings among the 5 clusters. Conclusion: The results showed that there were differences in clinical and radiological findings among patients with systemic sclerosis-specific autoantibodies.

Autoimmune diseases in patients with pemphigus and their first‐degree relatives

Pemphigus is an autoimmune blistering disease affecting the skin and mucosa, which mostly in anecdotal reports has been associated with several autoimmune diseases. The aim of this study was to assess the frequency of autoimmune diseases in a large group of patients with pemphigus and their first-degree relatives. One hundred and ten patients with pemphigus were interviewed for the existence of various autoimmune diseases. Patients' sera were examined for the presence of several autoantibodies. The existence of autoimmune diseases in 969 first-degree relatives of the patients was assessed via questionnaires. Seven of 110 (6.3%) patients with pemphigus had concurrent autoimmune diseases, including four (3.6%) with autoimmune thyroid disease and three (2.7%) with rheumatoid arthritis. Ten of 969 (1.03%) first-degree relatives of patients with pemphigus had autoimmune thyroid disease, three (0.31%) had rheumatoid arthritis, and three (0.31%) had type 1 diabetes mellitus. The patient's group had a statistically significant higher prevalence of thyroid disease and rheumatoid arthritis than their first-degree relatives (P = 0.046 and 0.016 respectively). Patients with pemphigus seem to have a higher rate of autoimmune thyroid disease and rheumatoid arthritis than both the general population and their own first-degree relatives. Further studies comparing patients with pemphigus with healthy controls are needed to stratify their risk factors for developing other autoimmune diseases and to define guidelines regarding diagnosis and treatment of coexistent autoimmune disorders.

Remission and Relapse of Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a type of chronic pancreatitis characterized by swelling of the pancreas, narrowing of the main pancreatic duct, elevation of serum immunoglobulin G or G4 level or presence of several autoantibodies, or lymphoplasmacytic infiltration and fibrosis in the pancreas. However, the pathogenesis of AIP remains unclear, and the natural history and long-term prognosis of AIP are little known. Oral corticosteroid therapy for AIP is recommended. The absolute indications for steroid therapy for AIP are bile duct stenosis and accompanying systemic disease such as retroperitoneal fibrosis and diabetes mellitus. The dosage for remission induction is 30 to 40 mg/d for 1 to 2 months. The remission maintenance is needed to prevent relapse, and 5 to 10 mg/d for at least 6 months is recommended in patients who do not have complete remission. When relapse occurs, the dose used at remission induction can be readministered. Herein, we discuss remission and relapse of AIP, focusing on corticosteroid treatment to help clinicians care for patients with AIP and to help make an ideal treatment protocol of AIP through a review of published data. We tried to define remission and relapse of AIP to help investigate the natural course of AIP.

Spectrum of Autoantibodies in Tunisian Adult Type 1 Diabetes Mellitus

As an autoimmune disease, type 1 diabetes mellitus (T1DM) is characterized by the presence of several autoantibodies. The aim of this study was to examine a broad spectrum of antibodies in Tunisian adult T1DM and to compare their prevalence with a healthy control group. Two hundred sixty-one diabetics and 100 healthy blood donors were enrolled in this study. Indirect immunofluorescence was performed for the detection of islet cell, antiendomysial, antinuclear, antimitochondrial, antismooth muscle, antireticulin, and antikeratin antibodies. Enzyme-linked immunosorbent assay was used for measuring anticardiolipin, antigliadin, antitransglutaminase, and antithyroperoxidase antibodies. Latex agglutination was used for the detection of rheumatoid factors. As expected, islet cell antibodies were the most frequent (33.7%). Antigliadin, antithyroperoxidase, and antikeratin antibodies were relatively frequent (18%, 15.3%, and 10.3%, respectively) and were statistically more prevalent in diabetics than in controls. There was no correlation between diabetes duration and any autoantibody, except for islet cell antibodies that were more frequent at the onset of diabetes. Several autoantibodies nonspecific of diabetes are frequent in diabetic patients, which may be associated with or predictors of some autoimmune diseases, and can also reflect a special profile of autoimmunity in diabetics in comparison to healthy controls.

Anti-DNA topoisomerase II α autoantibodies in Japanese patients with systemic sclerosis

The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti-DNA topoisomerase II alpha antibody (anti-topo II alpha Ab) remains unknown in Japanese patients with SSc. To determine the prevalence and clinical correlation of anti-topo II alpha Ab in Japanese patients with SSc. Serum samples were obtained from 103 Japanese patients with SSc. Control serum samples were obtained from 43 healthy Japanese volunteers. Anti-topo II alpha Abs were determined by enzyme linked-immunosorbent assay.IgG anti-topo II alpha Ab levels were significantly increased in SSc patients (n=103) compared to normal controls (n=43; P<0.005). IgG or IgM anti-topo II alpha Ab was detected in 19% (20/103) of SSc patients when absorbance values higher than the mean+2SD of control serum samples were considered positive. By contrast, IgG or IgM anti-topo II alpha Ab was observed in only 7% (3/43) of healthy individuals. The presence of pulmonary fibrosis was more frequently detected in SSc patients with IgG anti-topo II alpha Ab than those without the Ab (P<0.05). Moreover, % DLco and % VC were significantly decreased in SSc patients with anti-topo II alpha Ab relative to those without the Ab (P<0.05 and P<0.01, respectively). The elevated levels of both erythrocyte sedimentation rate and C-reactive protein were also more frequently observed in SSc patients positive for IgG anti-topo II alpha Ab (P<0.005). The results of the present study indicate that anti-topo II alpha Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc.

Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a generalized connective tissue disease which is characterized by the presence of several autoantibodies. To determine the prevalence and antigen specificity of anti-U1RNP antibodies (anti-U1RNP) in patients with SSc, serum samples from 223 patients with SSc, 117 patients with systemic lupus erythematosus (SLE), 18 patients with mixed connective tissue disease (MCTD) and 40 healthy control subjects were examined by indirect immunofluorescent analysis (IIF), double immunodiffusion, and immunoblotting using nuclear extract of HeLa cells. Eighteen of the 223 (8%) serum samples from patients with SSc were shown to be positive for anti-U1RNP. The frequency of anti-U1RNP positivity in limited cutaneous SSc (14%) was significantly higher than that in those with diffuse cutaneous SSc (3%). Anti-Sm antibodies were detected in patients with SLE positive for anti-U1RNP, but not in those with SSc positive for anti-U1RNP or those with MCTD. Immunoblotting demonstrated that anti-70-kD antibodies were detected more often in patients with SSc positive for anti-U1RNP and in those with MCTD than in those with SLE. Furthermore, anti-U1RNP was closely correlated with pulmonary fibrosis and joint involvement in patients with SSc. These results suggest that anti-70-kD antibodies are useful in the classification of patients with anti-U1RNP.

Gravesʼ hyperthyroidism in a patient with primary sclerosing cholangitis. Coincidence or combined pathogenesis?

Several autoimmune disorders have been associated with the diagnosis of primary sclerosing cholangitis (PSC). We report on a 19-year-old male PSC patient with a history of ulcerative colitis who developed hyperthyroidism consistent with Graves' disease. In contrast to primary biliary cirrhosis, hyperthyroidism appears to be very uncommon in PSC patients. Nevertheless, the rarity of Graves' disease in young males, the presence of a human leucocyte antigen (HLA) phenotype often encountered in both Graves' disease and PSC and the presence of several autoantibodies suggest a common immunogenetic predisposition, rather than mere coincidence, of both diseases in this patient. Since many patients with thyroid disease exhibit mild cholestatic liver function abnormalities but few of them undergo cholangiographic examination, PSC may be underdiagnosed. Physicians should therefore be aware of the potential association between thyroid disease and PSC.

Effect of cyclophosphamide on lymphokine production in MRL/lpr.Yaa mice.

The Y chromosome (Yaa gene) from autoimmune BXSB mice has been shown to be responsible for the acceleration of autoimmune symptoms when transferred to MRL/lpr mice. We examined the pathological, serological and immunological characteristics of MRL/lpr. Yaa mice and the suppressive effect of cyclophosphamide (CP) on the mice. MRL/lpr. Yaa mice spontaneously developed a massive lymphadenopathy characterized by hypergammaglobulinemia, the presence of several autoantibodies, and autoimmune disease. In MRL/lpr. Yaa mice, IL-2, IL-4 and IL-5 production in concanavalin A (Con A)-stimulated splenocytes were about 10-fold lower than in BALB/c mice at 5 weeks of age. The concentrations of these lymphokines remained low until the mice were 16 weeks of age. The production of IFN-gamma and IL-6 in 16 week old MRL/lpr. Yaa mice was about 4- and 2-fold lower, respectively, though these levels were similar in both strains at 8 weeks of age. It was found that this dysregulation of T cell function was almost identical to that in MRL/lpr mice. Administration of CP to MRL/lpr. Yaa mice ameliorated nephritis, and suppressed production of autoantibodies and the accumulation of abnormal T cells. CP also significantly elevated the production of lymphokines. These findings suggest that an abnormality of T cell function may contribute to the autoimmune pathogenesis of MRL/lpr. Yaa mice and that CP probably ameliorates auto-immune disease by improving the T cell functions.

Factors related to the presence of autoantibodies in patients with chronic mental disorders

Serum samples from 307 patients with various chronic mental disorders were examined for the presence of several autoantibodies. Autoantibodies detected included antinuclear antibodies (ANA) in 122 307 (39.7%), rheumatoid factor (RF) in 23 307 (7.5%), anticardiolipin antibodies (anti-CL) in 23 304 (7.6%, IgM in 12 patients, IgM in 13 patients). Isolated cases with IgG anti-dsDNA, anti-Ro(SSA), and anti-Ro(SSA)/anti-La(SSB) were also identified. The analysis of data revealed that the aging process in patients studied contributed significantly to the incidence of ANA (p < 0.0001) and RF (p < 0.01). In addition, the chronic administration of chlorpromazine (CPZ) was associated with the presence of ANA (p < 0.03) as well as with the presence of IgM and/or IgG anti-CL antibodies (p < 0.003). Finally, the diagnosis of schizophrenia correlated with the presence of ANA (p < 0.001). This study represents the autoantibody profile of patients with chronic mental disorders and emphasizes the multifactorial origin of autoantibody response in psychiatric patients.

Clinical and immunologic response to Isoprinosine in alopecia areata and alopecia universalis: Association with autoantibodies

Twenty patients with alopecia universalis, alopecia semiuniversalis and alopecia areata were studied for their immune parameters. Fourteen of them received an oral treatment with Isoprinosine, a synthetic immunomodulator. Ten patients showed the presence of several autoantibodies. No significant abnormalities in various T cell rosette markers were found, but T4/T8 ratios tended to be elevated. Erythrocyte antibody complement (EAC) rosettes were usually decreased. Treatment with Isoprinosine produced a clinical response, as judged by total or partial hair growth, in nine of the fourteen patients treated. It was striking to observe that seven of the nine responders had autoantibodies prior to treatment. These autoantibodies disappeared or decreased with Isoprinosine therapy. In contrast, only one of five nonresponders had serum autoantibodies. After treatment, both groups showed an increase in blood-active T rosettes. These results suggest that alopecia is a heterogeneous disease subdivided by the presence or absence of autoantibodies since clinical response was mainly obtained in patients presenting autoantibodies.

Auto-antibodies in affective disorders

1. 1. One hundred depressive patients were tested for the presence of several auto-antibodies. 2. 2. Rheumatoid factor — tested with three different techniques-, antinuclear antibodies, and two other auto-antibodies (antimitochondrial and anti-basemembrane antibodies) could not be found in a higher frequency than in normals, whereas the occurrence of the thyroglobulin auto-antibodies was just above the upper limit of normals. 3. 3. Factors eventually influencing the results and directions for further work are discussed on the basis of previous studies.