Existence Of Autoantibodies Research Articles

The humoral immune landscape in Parkinson's disease: Unraveling antibody and B cell changes.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) in the brain and progressive loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Although the role of neuroinflammation and cellular immunity in PD has been extensively studied, the involvement of humoral immunity mediated by antibodies and B cells has received less attention. This article provides a comprehensive review of the current understanding of humoral immunity in PD. Here, we discuss alterations in B cells in PD, including changes in their number and phenotype. Evidence mostly indicates a decrease in the quantity of B cells in PD, accompanied by a shift in the population from naïve to memory cells. Furthermore, the existence of autoantibodies that target several antigens in PD has been investigated (i.e., anti-α-syn autoantibodies, anti-glial-derived antigen antibodies, anti-Tau antibodies, antineuromelanin antibodies, and antibodies against the renin-angiotensin system). Several autoantibodies are generated in PD, which may either provide protection or have harmful effects on disease progression. Furthermore, we have reviewed studies focusing on the utilization of antibodies as a potential treatment for PD, both in animal and clinical trials. This review sheds light on the intricate interplay between antibodies and the pathological processes in PD, including complement system activation.

Synergistic effects of immune checkpoints and checkpoint inhibitors in inflammatory neuropathies: Implications and mechanisms.

Immune checkpoint molecules play pivotal roles in the regulation of immune homeostasis. Disruption of the immune checkpoints causes autoimmune/inflammatory as well as malignant disorders. Over the past few years, the immune checkpoint molecules with inhibitory function emerged as potential therapeutic targets in oncological conditions. The inhibition of the function of these molecules by using immune checkpoint inhibitors (ICIs) has brought paradigmatic changes in cancer therapy due to their remarkable clinical benefits, not only in improving the quality of life but also in prolonging the survival time of cancer patients. Unfortunately, the ICIs soon turned out to be a "double-edged sword" as the use of ICIs caused multiple immune-related adverse effects (irAEs). The development of inflammatory neuropathies such as Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as the secondary effects of immunotherapy appeared very challenging as these conditions result in significant and often permanent disability. The underlying mechanism(s) through which ICIs trigger inflammatory neuropathies are currently not known. Compelling evidence suggests autoimmune reaction and/or inflammation as the independent risk mechanism of inflammatory neuropathies. There is a lack of understanding as to whether prior exposure to the risk factors of inflammatory neuropathies, the presence of germline genetic variants in immune function-related genes, genetic variations within immune checkpoint molecules, the existence of autoantibodies, and activated/memory T cells act as determining factors for ICI-induced inflammatory neuropathies. Herein, we highlight the available pieces of evidence, discuss the mechanistic basis, and propose a few testable hypotheses on inflammatory neuropathies as irAEs of immunotherapy.

Sars-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

Abstract Background Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose We want to determine i) the degree of homology between SARS-CoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was funded by the Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), the Fondation de Bienfaisance du Groupe Pictet, the Fondation Ancrage, the Fondation Privée des HUG, and the Center for Emerging Viral Diseases. The De Reuter (grant Nr 657) and the Schmidheiny Foundation.

Myositis autoantibodies in Iranian myositis patients: assessment the frequency and clinical relevancy.

Dermatomyositis (DM) and polymyositis (PM) are known as two major types of idiopathic inflammatory myopathies (IMMs). During the past years, growing data strongly suggest the clinical significance of myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs). The present study aimed to determine the profile of MSAs and MAAs, subsequently to address the clinical significance of these autoantibodies in Iranian myositis patients. In this cross-sectional study, 28 DM and 24 PM patients were entered. Demographic and clinical characteristics were collected by direct examination and patients' medical record. The existence of MSAs and MAAs was assessed by indirect immunofluorescence then using immunoblotting (FA 1510-1005-1, DL 1530-1601-4 G; Euroimmun, Germany). Data were analyzed using the SPSS software (v22; SPSS Inc. Chicago, IL, USA). The mean age of the patients was 46.18 ± 12.95years and male/female ratio was 28.8/71.2. Autoantibodies were positive in 63.46% of myositis patients. Interestingly, anti-TIF1γ and anti-PL7 were significantly associated with malignancy (P < 0.001, P = 0.008; respectively). The existence of autoantibody and anti-Jo1 had significant relation with interstitial lung disease (ILD) (P = 0.034, P = 0.006; respectively). Joint involvements including arthritis and arthralgia were significantly associated with anti-Ro52 and anti-Jo1 (P = 0.04, P = 0.02; respectively). Taken together, it can be concluded that certain myositis autoantibodies present clinical significance which is in line with the literature. The use of these autoantibodies as biomarkers by line blotting along with indirect immunofluorescence facilitates diagnosis of inflammatory myopathies and makes it more accurate as well as better management of myositis patients if used based on a science-based manner. Key Points • Identification of MSAs and MAAs facilitates the diagnosis of inflammatory myopathies and provides better myositis patient's management if used according to a science-based manner. • Anti-rod and ring antibody was detected in a patient with ovarian cancer-induced dermatomyositis. • Malignancy and ILD are integrated parts of myositis which can be associated with MSAs and MAAs.

A NEVER-ENDING STORY OF RHEUMATOID ARTHRITIS

There are distinct Rheumatic disorders, still Rheumatoid arthritis (RA) is believed to be very prevailing. RA is an empathic disorder described over integral redness, constant inflammation, and the existence of auto-antibodies. In RA, inflammation in joints, loss of motion of joint stiffness, joint tenderness are most common in patients. Deformity of joints can be prevented by early diagnosis and treatment. The extremity of the disease can be reduced by combining the drugs and improved weight more profiled than single medication. Treat-to-target progress results in a superior-conclusion in RA, and the ACR, EULAR, and other specialized systems have supported treat-to-target as a basic curative strategy for RA. The novel methods used in RA have upgraded the development of the disorder and maximum people helpful in cancellation of clinical manifestations if the identification of disorder takes place before time. This review article is written after studying most of the journal’s articles, which were published between 1997-2019.

Humoral response in experimental autoimmune encephalomyelitis targets neural precursor cells in the central nervous system of naive rodents

BackgroundNeural precursor cells (NPCs) located in the subventricular zone (SVZ), a well-defined NPC niche, play a crucial role in central nervous system (CNS) homeostasis. Moreover, NPCs are involved in the endogenous reparative process both in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the possibility that NPCs may be vulnerable to immune-related components may not be ruled out. Therefore, we investigated the potential affinity of myelin oligodendrocyte glycoprotein (MOG)-induced humoral response(s) to NPCs.MethodsMOG35–55-EAE was induced in C57BL/6 mice; blood-sampling was performed on days 17–21 (acute phase) along with a naive group and corresponding antisera (AS) were collected (EAE-AS, NAIVE-AS). The presence of anti-CNS autoantibodies was examined with western blotting. Furthermore, using the collected antisera and anti-MOG antibody (as positive control), immunohistochemistry and double immunofluorescence were implemented on normal neonatal, postnatal, and adult mouse brain sections. Targeted NPCs were identified with confocal microscopy. In vitro immunoreactivity assessment on NPCs challenged with autoantibodies was evaluated for apoptotic/autophagic activity.ResultsWestern blotting verified the existence of autoantibodies in EAE mice and demonstrated bands corresponding to yet unidentified NPC surface epitopes. A dominant selective binding of EAE-AS in the subventricular zone in all age groups compared to NAIVE-AS (p < 0.001) was observed. Additionally, anti-BrdU+/EAE-AS+ colocalization was significantly higher than anti-BrdU+/anti-MOG+, a finding suggesting that the EAE humoral response colocalized with NPCs(BrdU+), cells that do not express MOG. Well-established NPC markers (Nestin, m-Musashi-1, Sox2, DCX, GFAP, NG2) were used to identify the distinct cell types which exhibited selective binding with EAE-AS. The findings verified that EAE-AS exerts cross-reactivity with NPCs which varies throughout the neonatal to adult stage, with a preference to cells of early developmental stages. Finally, increased expressions of Caspase 3 and Beclin 1 on NPCs were detected.ConclusionWe provide evidence for the first time that MOG35–55 EAE induces production of antibodies with affinity to SVZ of naive mice in three different age groups. These autoantibodies target lineage-specific NPCs as brain develops and have the potential to trigger apoptotic pathways. Thus, our findings provide indication that cross-talk between immunity and NPCs may lead to functional alteration of NPCs regarding their viability and potentially oligodendrogenesis and effective remyelination.

The roles and applications of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours.

The existence of autoantibodies towards an individual's own proteins or nucleic acids has been established for more than 100years, and for a long period, these autoantibodies have been believed to be closely associated with autoimmune diseases. However, in recent years, researchers have become more interested in the role and application of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours. Over the past few decades, numerous epidemiological studies have shown that the risk of certain cancers is significantly altered (increased or decreased) in patients with autoimmune diseases, which suggests that autoantibodies may play either promoting or suppressing roles in cancer progression. The idea that autoantibodies are directly involved in tumour progression gains special support by the findings that some antibodies secreted by a variety of cancer cells can promote their proliferation and metastasis. Because the cancer cells generate cell antigenic changes (neoantigens), which trigger the immune system to produce autoantibodies, serum autoantibodies against tumour-associated antigens have been established as a novel type of cancer biomarkers and have been extensively studied in different types of cancer. The autoantibodies as biomarkers in cancer diagnosis are not only more sensitive and specific than antigens, but also could appear before clinical evidences of the tumours, thus disclosing them. The observations that cancer risk is lower in patients with some autoimmune diseases suggest that certain autoantibodies may be protective from certain cancers. Moreover, the presence of autoantibodies in healthy individuals implies that it could be safe to employ autoantibodies to treat cancer. Of note, an autoantibodies derived from lupus murine model received much attention due to their selective cytotoxicity for malignant tumour cell without harming normal ones. These studies showed the therapeutic value of autoantibodies in cancer. In this review, we revisited the pathological or protective role of autoantibodies in cancer progression, summarize the application of autoantibodies in cancer diagnosis and prognosis, and discuss the value of autoantibodies in cancer therapy. The studies established to date suggest that autoantibodies not only regulate cancer progression but also promise to be valuable instruments in oncological diagnosis and therapy.

Genetic aspects of primary hyperaldosteronism and pheochromocytoma

Pheochromocytoma and primary hyperaldosteronism are the most common causes of secondary hypertension. In a group of patients with primary hyperaldosteronism the prevalence of somatic mutation has been established in patients with aldosterone-producing adenomas (APA), genetic mutations have been identified in patients with familytypes of the disease. The authors declare that aldosterone-producing cellular clusters, which derived from zona glomerulosa, appear as a result of somatic mutations and might be a precursor of APA. Development of bilateral adrenal hyperplasia and APA might be explained by an existence of autoantibodies and their chronic stimulation of zona glomerulosa. The assessment of somatic and germline mutations in patients with pheochromocytoma and paraganglioma facilitates early diagnostics other tumors within syndromic neoplasia. Implementation of new genetic test in practice would improve early diagnosis of adrenal pathology in hypertensive patients.

Elevated natural killer cell levels and autoimmunity synergistically decrease uterine blood flow during early pregnancy.

ObjectiveTo investigate whether natural killer (NK) cell and autoimmune antibody acts synergistically, by the action of autoantibodies to increase NK cell number and cytotoxicity, to decrease uterine blood flow during early pregnancy in pregnant women with a history of recurrent spontaneous abortion (RSA).MethodsSeventy-five pregnant women (between 5 and 7 weeks gestation) with a history of unexplained RSA were included in the study group. Forty-one pregnant women without a history of RSA were included as controls. All women with a history of RSA were tested for autoantibodies and number of peripheral blood natural killer (pbNK) cell by flow cytometry. Study populations were stratified into four groups by existence of autoantibody and degree of increase of pbNK cells. The uterine radial artery resistance index (RI) was measured by color-pulsed Doppler transvaginal ultrasound.ResultsThe mean RI of the autoimmune antibody-positive (AA+) group (0.63±0.09) was significantly higher than that of the normal control group (0.53±0.10, P=0.001). The mean RI of the AA+/only-NK elevated (eNK) group (0.63±0.09) was significantly higher than those of the only-AA+ group (0.55±0.07, P=0.019) and the only-eNK group (0.57±0.07, P=0.021).ConclusionConcurrent elevation in NK cells and autoimmunity results in decreased uterine blood flow during early pregnancy. However, the majority of cases of RSA remain unexplained and larger scale studies are needed to confirm our conclusion and to develop diagnostic and therapeutic plans for women with a history of RSA.

Vitamin D status in systemic lupus erythematosus patients and its association with selected clinical and laboratory parameters

To identify relationships between vitamin D serum levels and the presence of autoantibodies directed against vitamin D and levels of interleukin(IL)-17 and IL-23 in patients with systemic lupus erythematosus (SLE). The study included 49 patients with SLE. Serum concentrations of 25(OH)D(3) were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH)(2)D(3) and levels of IL-17 and IL-23 in serum of SLE patients. In evaluation of vitamin D status, the control group consisted of 49 age and gender matched healthy individuals, whereas in assessment of anti-vitamin D antibodies the control group comprised 30 sera from blood donors. Serum concentration of 25(OH)D(3) in SLE patients during the warm season was 18.47 ± 9.14 ng/ml, which was significantly decreased as compared with that of the control group - 31.27 ± 12.65 ng/ml (p = 0.0005). During the cold season a trend toward lower concentration of 25(OH)D(3) in SLE patients was revealed; however, it did not reach statistical significance (11.71 ± 7.21 ng/ml vs. 16.01 ± 8.46 ng/ml; p = 0.054). Results within the recommended range for vitamin D (30-80 ng/ml; 70-200 nmol/l) were observed only in three patients. The 25(OH)D(3) concentration was decreased in SLE patients with renal disease or leucopenia as compared with the levels in patients who did not have either problem (p = 0.006 and p = 0.047, respectively). The cold season was found to be a risk factor for vitamin D deficiency (<20 ng/ml) (odds ratio = 9.25; p = 0.005). Autoantibodies directed against 1,25(OH)(2)D(3) were detected in three SLE patients. No significant difference in 25(OH)D(3) serum concentrations was found between SLE patients with and without these autoantibodies. No link was shown between the existence of autoantibodies against 1,25(OH)(2)D(3) and clinical or laboratory findings, including IL-17 and IL-23 levels. However, serum concentrations of IL-23 were lower in patients with vitamin D deficiency (p = 0.037). SLE patients, especially those with leucopenia or renal involvement, are at high risk of vitamin D deficiency and require vitamin D supplementation. Some SLE patient sera contained 1,25(OH)(2)D(3) antibodies, but these antibodies do not appear to affect vitamin D levels.

Immunfluoreszenz

The existence of autoantibodies is characteristic of several rheumatic diseases and indicates impaired self-tolerance. The analysis and detection of these autoantibodies represent an important factor in the diagnosis of rheumatic diseases. Immunofluorescence is an important technique in basic science and also one of the most commonly used techniques for the characterization of autoantibodies in clinical medicine thus facilitating the diagnosis and evaluation of rheumatic diseases. Addition of serum samples from individual patients to an antigen substrate (present in fixed cells or tissue) results in a specific reaction between the autoantibodies and the respective antigens. Incubation with a second, fluorescence-linked, anti-human antibody which binds to the primary antigen-bound autoantibodies from patient serum results in fluorescence patterns which are characteristic of certain rheumatic diseases.

Anti-ribonucleoproteins autoantibodies in patients with systemic autoimmune diseases. Relation with cutaneous photosensitivity

A common feature between patients with a certain group of systemic autoimmune pathologies (SAPs) with rheumatic component, such as lupus erythematosus (LE) in all its forms, is the presence of cutaneous photosensitivity (CP) as well as the existence of autoantibodies (Aabs). These Aabs have also high incidence in other SAPs that do not present CP, like primary Sjögren's syndrome and rheumatoid arthritis. Cutaneous photosensitivity is a condition that consists of an exacerbated skin reaction to solar radiations; its incidence can reach 90% in systemic LE. The mechanisms involved in the development of CP have been extensively studied focusing on different approaches; however, the exact mechanism has not been fully elucidated yet. There are many theories that relate specifically the presence of circulating anti-Ro/SS-A Aabs with the CP phenomenon, though there are several studies which are in disagreement. In this study, we evaluated the Aabs profile (anti-Ro/SS-A 52kDa, anti-Ro/SS-A 60kDa, anti-La/SS-B, anti-Sm and ANAs) as well as their titer or reactivity, in a local cohort of 169 patients with SAPs. We related those Aabs profiles and titers with the presence or absence of CP, and we found that there was no significant association between the presence of anti-Ro/SS-A Aabs and the occurrence of CP. On the other hand, a statistically significant positive association was found between CP and high reactivity anti-Sm Aabs, though this fact could be biased by the incidence of both events in SLE patients. To sum up, in the particular population studied, there is no direct relationship between anti-Ro/SS-A Aabs and CP, which is in agreement with some authors and in disagreement with many others, contributing to the endless discussion of this issue.

An analysis of the prevalence of thyroid autoantibodies: thyroid peroxidase antibodies (ATA) and thyroglobulin antibodies (ATG) in children with newly diagnosed diabetes mellitus type 1 during 2000–2004 in the Upper Silesia region, Poland

The aim of this study was to evaluate the prevalence of thyroid autoantibodies and clinical significance of thyroid autoimmunity in children with the diagnosis of diabetes mellitus type 1. The study group comprised 222 children all with newly diagnosed diabetes mellitus type 1 (122 boys) with a mean age 9.92 +/- 4.5 years, who were admitted to a regional diabetes division in 2000-2004. Assessment of ATA and ATG were performed and two emerging groups-ATA/ATG (+) and ATA/ATG (-) were compared, including anthropometric data, HbA1C, plasma lipids, TSH, fT4. Positive antibodies titre was found in 27 (12.16%) of the children. Apart from older age in the antibody positive group (11.67 vs. 9.67 years, p < 0.05), there were no significant differences among these groups regarding other clinical and laboratory characteristics. Concluding, the presence of thyroid autoantibodies in 12.16% of subjects with newly diagnosed diabetes confirms the necessity of screening of all children, especially adolescents from the time of diagnosis of diabetes mellitus type 1 onwards. No association between existence of autoantibodies and the clinical status of a child at the presentation of diabetes was demonstrated by this study.

Increased Serum Anti-Carbonic Anhydrase II Antibodies in Patients with Graves' Disease

Carbonic anhydrase II (CA II) has an important role in thyroid hormone synthesis via regulating iodide (I-) transport across thyroidal cell membranes and the existence of autoantibodies against CA I and/or CA II have been shown in sera from patient with various autoimmune diseases such as Sjögren's Syndrome, Systemic Lupus Erythmatosus, type 1 diabetes, primary biliary cirrhosis and ulcerative colitis. The aim of this study was to investigate the presence of anti-CA I and CA II antibodies in autoimmune thyroid disease and the relationships between the autoantibodies and other clinical parameters. We studied 40 autoimmune thyroid patients (20 Hashimoto's thyroiditis, HT and 20 Graves' disease, GD ) and 21 healthy control subjects. Serum anti-CA I and CA II antibodies were screened by ELISA. Positive rate of anti-CA II (25%) antibody was significantly higher in GD patients as compared to HT patients and control subjects (p<0.05). There were no significant changes in positive rate of anti-CA I antibody. In addition, a significant correlation between serum anti-CA antibodies titers and other studied clinical parameters was not found. The results suggest that anti-CA II antibodies may be involved in the pathogenesis of GD.

Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity

Autoimmune connective tissue diseases are chronic, potentially life threatening complex multisystem disorders. Their etiology is unknown but genetic, hormonal and environmental factors are important. The clinical disease is preceded by a long period of time (sometimes many years) when the patients can be identified by characteristic antibodies in their serum. When such a patient is identified he is usually followed and treated if clinical disease manifests itself. However, other factors besides the existence of autoantibodies have a predictive value for those disorders; some of them hereditary or genetic, and can be used only to predict likelihood of future disease, and others, connected to lifestyle and environment, could be modified in order to try and prevent it. Several non-randomized small scale studies have suggested that autoimmune disease could be prevented if treated aggressively prior to manifestations of symptoms. However, if such is the case, criteria would have to be formalized for selection of patients for this preventive treatment. Only patients whose probability to develop clinical disease is higher then a certain threshold should be treated while asymptomatic. The aim of this article is to review the major risk factors for autoimmune disease, both hereditary and environmental, and so to help define those future criteria. Individuals who are at risk to develop an autoimmune disease should be advised to refrain from activities and lifestyle which endangers their health and quality of life.

Inflammatory Bowel Disease-Specific Autoantibodies in HLA-B27-Associated Spondyloarthropathies: Increased Prevalence of ASCA and pANCA

Aims: An association between inflammatory bowel disease (IBD) and spondyloarthropathies (SpA) has repeatedly been reported. The aim of the present study was to investigate whether serologic markers of IBD, e.g. antibodies against Saccharomyces cerevisiae (ASCA), antibodies against exocrine pancreas (PAB) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) are present in HLA-B27-associated SpA. Methods: 87 patients with HLA-B27-positive SpA and 145 controls were tested for ASCA, PAB and pANCA employing ELISA or indirect immunofluorescence, respectively. Antibody-positive patients were interviewed regarding IBD-related symptoms using a standardized questionnaire. Results/Conclusion: When compared to the controls, ASCA IgA but not ASCA IgG levels were significantly increased in patients with SpA, in particular in ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). pANCA were found in increased frequency in patients with SpA whereas PAB were not detected. The existence of autoantibodies was not associated with gastrointestinal symptoms but sustains the presence of a pathophysiological link between bowel inflammation and SpA.

Detection of IgG-bound lipoprotein(a) immune complexes in patients with coronary heart disease

Background: LDL-immune complexes (IC) have a powerful pathogenic role for inducing foam cell formation in vitro more efficiently than any other known mechanism. Studies have also shown that plasma LDL-IC concentration is a powerful marker for the development of atherosclerosis. The structure, fatty acid composition and antioxidant concentrations of Lp(a) and LDL are quite similar. The same oxidation pattern has also been described for both lipoproteins. Modified forms of Lp(a), some resembling oxidized Lp(a), have been identified in human atheromatous lesions. The existence of autoantibodies against MDA-Lp(a) in vivo is also presented. Therefore, we suppose that Lp(a) might trigger an immune response leading to the production of autoantibodies and subsequently to the formation of immune complexes. This study examined the existence of IgG-bound Lp(a)-IC and investigated its value as a risk factor for the development of atherosclerosis. Methods: We developed two “sandwich” ELISAs for measuring plasma Lp(a)-IC and LDL-IC concentrations, using anti-human IgG(Fab) as the capture antibody, and quantitating with monoclonal anti-apo(a) or anti-apoB enzyme conjugate. Their concentrations were studied in 160 patients with coronary heart disease (CHD) and 290 control subjects. Results: Plasma TC, LDL-C, TG and apoB concentrations in CHD patients were all significantly increased, whereas HDL-C and apoAI concentrations were decreased. The Lp(a) concentrations in the patients with CHD were also significantly different from those of control (262.4±220.0 vs. 211.3±199.4 mg/l, P<0.005). Plasma Lp(a)-IC (2.24±1.71 vs. 1.62±1.50 AU, P<0.0001) and LDL-IC (2.77±1.29 vs. 1.40±0.92 AU, P<0.0001) concentrations in patients with CHD were both significantly higher than those of control. The relationships between Lp(a)-IC, LDL-IC concentrations and other lipid traits in all the studied subjects ( n=450) were carried out. LDL-IC concentrations were positively correlated with LDL-C, apoB, TC, TG and Lp(a) concentrations, while negatively correlated with HDL-C and apoAI concentrations, respectively. Similarly, Lp(a)-IC concentrations were positively correlated with Lp(a), LDL-C, apoB and TC concentrations, while negatively correlated with HDL-C and apoAI concentrations, respectively. Furthermore, a significantly positive relation between LDL-IC and Lp(a)-IC concentrations was also found ( r=0.313, P<0.0001). Conclusions: We report the existence of Lp(a)-IC in both the plasma of patients with CHD and control subjects. Lp(a)-IC concentration increases in the CHD patients.

Idiotypic network dysregulation: a common etiopathogenesis of diverse autoimmune diseases.

The pathogenesis of autoimmune disease is still an enigma. Whereas the diverse clinical manifestations of many autoimmune diseases cannot be explained by the existence of autoantibodies, idiotypic dysregulation may provide an alternative explanation. Experimental models, serum level changes of pathogenic idiotypes during exacerbation and remission, and the increased expression of pathogenic idiotypes following common infections all support this notion. In this article we review experimental models of autoimmune disease induction (systemic lupus erythematosus, antiphospholipid syndrome, Goodpasture's syndrome, autoimmune thyroiditis, and vasculitis) by manipulation of the idiotypic network, and discuss the utilization of idiotypes for the immunotherapy of autoimmune diseases and other conditions that involve the immune system (e.g., atherosclerosis).

Antinuclear autoantibodies in patients with inflammatory bowel disease. High prevalence in first-degree relatives.

Crohn's disease and ulcerative colitis show a familial aggregation. The role of antinuclear autoantibodies, which occur in both diseases, remains to be defined. In 76 patients with Crohn's disease, 61 patients with ulcerative colitis, 105 first-degree relatives of patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 40 healthy unrelated controls antinuclear autoantibodies were detected by indirect immunofluorescence. Existence of autoantibodies was correlated with clinical features. Eighteen percent of patients with Crohn's disease (14/76), 43% of patients with ulcerative colitis (26/61), 13% of relatives of patients with Crohn's disease (14/105), 24% of relatives of ulcerative colitis patients (24/101), and 2% of the healthy controls (1/40) were positive for antinuclear autoantibodies. The difference between controls and patients and the first-degree relatives of patients with ulcerative colitis, respectively, was statistically significant (P < or = 0.0144). In ulcerative colitis, the existence of antinuclear autoantibodies was negatively correlated with immunosuppressive therapy or extraintestinal manifestations (P = 0.0004 and 0.0273, respectively). Antinuclear autoantibodies may represent a factor disposing to the development of ulcerative colitis.

Antibodies to the collagen-like region of C1q and type II collagen are independent non-cross-reactive populations in systemic lupus erythematosus and rheumatoid arthritis.

The collagen-like region (CLR) of the first component of complement, C1q, and type II collagen are structurally similar, raising the possibility of epitopes in common, and of the existence of autoantibodies that are cross-reactive. Accordingly, antibodies to the CLR of C1q and to type II collagen were measured in patients' sera with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) by an ELISA. IgG antibodies to the CLR of C1q were present in 17% of patients with SLE but none with RA, and IgA antibodies were present in 10% and 8% of patients with SLE and RA, respectively. IgG antibodies to type II collagen were present in 15% and 25% of patients with SLE and RA, respectively, and IgA antibodies in 15% and 28% of patients with SLE and RA, respectively. There was no correlation in either disease between the serum levels of antibodies to the CLR of C1q and antibodies to type II collagen. For sera with antibodies to both antigens, neither competitive inhibition by ELISA nor preabsorption with the alternative antigen affected the level of reactivity to the other antigen. Thus antibodies to the CLR of C1q and antibodies to type II collagen are independent and non-cross-reactive populations, and presumably occur by different types of immunogenic stimulation.