Presence Of aAbs Research Articles

A comparative study of anti–ADAMTS-13 antibody dynamics in immune-mediated thrombotic thrombocytopenic purpura

BackgroundThrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management. ObjectivesTo compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti–ADAMTS-13 autoantibodies (AAbs) in patients with iTTP. MethodsThis study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL). ResultsFor ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [−0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (P < .001, Cohen’s g = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations. ConclusionWhile CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%.

Autoantibodies detection in patients affected by autoimmune retinopathies.

Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis.

Вплив антифосфоліпідних антитіл на ризик невдалої імплантації після запліднення in vitro

Infertility is a unique pathology because it concerns a couple, not one person, and is the cause of a whole range of medical, social, demographic and economic problems. With the active development of assisted reproductive technologies, the demand for solving the problem of infertility has grown significantly. However, the prevalence of infertility remains stable, indicating many «white» spots in the diagnosis and treatment of this pathology and determining the search for new risk factors, diagnostic criteria, and treatment algorithms. Purpose — to analyze the factors that may affect implantation, namely the presence of lupus anticoagulant and antiphospholipid antibodies in women with infertility who have undergone in vitro fertilization. Materials and methods. A survey of 106 women diagnosed with infertility underwent treatment with assisted reproductive technologies in September 2019 — February 2021. The control (1) group consisted of women who received infertility treatment according to the standard scheme: controlled ovarian stimulation, gamete collection, intracytoplasmic sperm injection and embryo transfer. The main (2) group included patients who received aspirin, anticoagulants, and intravenous IgG immunoglobulins in addition to the standard treatment regimen. In the present study, levels of lupus anticoagulant and antiphospholipid antibodies were determined in both groups. Results. The study found no differences between groups of patients in levels of antibodies (AB) to phospholipids (IgG), beta-2-glycoprotein (IgG, IgM) and lupus anticoagulant (screening, confirmation) in the two groups of patients (p&gt;0.05). Difference in two groups were in levels of AB to beta-2-glycoprotein IgM in controls, on average, 9.42 units/ml (5.86 units/ml — 12.35 units/ml), and in patients of main group — 7.23 units/ml (3.14 units/ml — 10.58 units/ml), p=0.015. One-factor logistic regression models were used to clinically understand the influence of factors associated with the risk of implantation failure. The analysis did not reveal a connection between risk of implantation failure and levels of autoantibodies (aAB) to phospholipids (IgG, IgM), beta-2-glycoprotein (IgG, IgM) and lupus anticoagulant (screening, confirmation) in two groups of patients (p&gt;0.05 in all cases). Conclusions. The presence of aAB and/or antiphospholipid syndrome during the establishment of infertility factors is an essential component of the algorithm for diagnostic search for the cause of infertility and miscarriage. However, based on the obtained data, the presence of aAB in the study does not affect the implantation process nor affects the treatment of infertility. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: infertility, implantation failure, antiphospholipid syndrome, assisted reproductive technologies.

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation.

Autoantibodies (AAb) and donor-specific HLA antibodies (DSA) are frequently present in pediatric liver transplant (LT) recipients. Their clinical significance remains incompletely understood. We aimed to investigate the prevalence of serum AAb and DSA in pediatric LT recipients and its correlation with patient characteristics and histological and biochemical parameters. We retrospectively reviewed the data from 62 pediatric LT patients in follow-up at Ghent University Hospital between January 2007 and February 2018. Blood samples with AAb measurement were taken systematically, liver biopsies (LB) were performed on clinical indication. AAb were detected in 27 (43.3%) patients, with antinuclear antibodies (ANA) being the most frequently (24%) encountered AAb. There was an association between AAb positivity and female gender (P = 0,032) and deceased donor LT (P = 0,006). Patients with positive AAb underwent a higher number of LB during their follow-up (P < 0,001), and an association was found with the presence of nonspecific histologic alterations (P = 0,032) in the absence of de novo autoimmune hepatitis. Positive AAb were also associated with higher alkaline phosphatase (P < 0,001), ALT (P < 0,001), AST (P < 0,001), γ-GT (P = 0,001), IgG (P = 0,011) and lower albumin (P = 0,029). Fourteen out of 50 (28%) patients were DSA-positive, mostly anti-HLA class II. DSA positivity was associated with T-cell-mediated rejection (P = 0,019), higher total (P = 0,033), and direct (P = 0,012) bilirubin and γ-GT (P < 0,001). The presence of AAb and DSA is associated with histological and biochemical parameters of graft dysfunction. Larger prospective studies are warranted to investigate the causal relationships between AAb and DSA development and outcome parameters post pediatric LT.

Abstract 3296: Tumor antigens Fetuin-A and Secreted Protein Acidic and Rich in Cysteine (SPARC) Autoantibodies as diagnostic and prognostic biomarkers in prostate cancer

Abstract Introduction: Improvements in blood-based biomarkers for distinguishing between indolent and aggressive prostate cancer are critical in enhancing the management of the disease. To address this, we have focused on the quantification of autoantibodies (AAbs) against tumor antigens present in the sera of patients. We have selected SPARC and Fetuin-A (also known as Alpha 2-HS Glycoprotein [AHSG]) for analysis as they are shown to be highly expressed at late stages of prostate cancer. The objectives of this study are: 1) To measure AAbs against SPARC and Fetuin-A in the sera of prostate cancer patients; 2) To determine whether there is a correlation between levels of SPARC and Fetuin-A AAbs in serum, disease and race status. Methods: Sera from prostate cancer patients and healthy controls were evaluated for AAbs against SPARC and Fetuin-A by using recombinant full-length proteins as substrates in an enzyme-linked immunosorbent assay (ELISA) assay. Sera from 117 Caucasian American (CA) n= and 111 African American (AA) prostate cancer patients with Gleason grades 6-10, and healthy controls (CA, n=52; AA, n=45) were analyzed in addition to sera from a biopsy cohort (n=99). The specificity of AAbs against the respective target proteins was confirmed by immunoblot analysis. Results: SPARC AAbs were detected in the sera, with significantly lower levels in both CA (p&amp;lt;0.0001; AUC=0.80), and AA prostate cancer patients (p&amp;lt;0.0001; AUC=0.82), compared to healthy controls. AAbs against Fetuin-A were significantly lower in prostate cancer patients in comparison to controls (p&amp;lt;0.0001; AUC=0.96). The range of AAb reactivity to SPARC and Fetuin-A was similar in both CA and AA prostate cancer patients. The results from biopsy cohort showed lower SPARC AAbs in cancer positive (n = 49) in comparison to cancer negative (n = 42) cases, and healthy controls. Conclusions: In this study, we established the presence of AAbs against SPARC in prostate cancer patient serum for the first time. More importantly, we observed highly significant differences between prostate cancer patient (low) and controls (high) sera, across different ethnic groups, similar to AAbs noted against Fetuin-A. These data support the further evaluation of SPARC and Fetuin-A AAbs as promising serum biomarkers for prostate cancer. Note: This abstract was not presented at the meeting. Citation Format: Shyh-Han Tan, Andy Martinez, Anshu Rastogi, Wei Huang, Sreedatta Banerjee, Lakshmi Ravindranath, Denise Young, Amina Ali, Indu Kohaar, Yongmei Chen, Jennifer Cullen, Gyorgy Petrovics, Albert Dobi, David G. McLeod, Jacob Kagan, Sudhir Srivastava, Isabell A. Sesterhenn, Inger L. Rosner, Shiv Srivastava, Alagarsamy Srinivasan. Tumor antigens Fetuin-A and Secreted Protein Acidic and Rich in Cysteine (SPARC) Autoantibodies as diagnostic and prognostic biomarkers in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3296.

Abstract 2830: Secreted protein acidic and rich in cysteine antigen and autoantibodies in sera of prostate cancer patients: Potential use in diagnosis /prognosis

Abstract Objectives: Improvements in blood based biomarkers for detecting clinically significant prostate cancer (CaP) or for distinguishing between indolent and aggressive CaP are critical in enhancing the management of this most common non-skin cancer of men in the US. These biomarkers include tumor associated antigens (TAAs) and autoantibodies (AAbs) against TAAs in patient sera. SPARC/Osteonectin is highly expressed in metastatic cancers (glioblastoma, melanoma, breast cancer and prostate cancer) and promotes bone metastasis and epithelial-mesemchymal transition. Our comparative transcriptome analyses of well/moderately differentiated CaP with poorly differentiated CaP, defined SPARC as central node in the network of genes with common regulatory elements (NKXH_NKXH_HOX) associating with poorly differentiated CaP. Further, we reported associations of high levels of SPARC mRNA or protein with Gleason 8-10 or poorly differentiated primary tumors and association with metastatic progression. The aims of this study are: i) Quantify SPARC antigen in the sera CaP patients; ii) Are AAbs against SPARC present in the serum of CaP patients?; iii) Is there a correlation between SPARC AAb level in patient sera and disease status? iii) Does SPARC AAb level vary according to distinct ethnic groups? Methods: Sera from CaP patients and healthy controls were evaluated for SPARC antigen using a commercial enzyme-linked immunosorbent assay (ELISA) kit. AAbs against SPARC were determined by ELISA utilizing recombinant full-length human SPARC protein as a substrate. For evaluation we used Caucasian American (CA, n=117) and African American (AA, n=111) CaP patients comprising Gleason 6-10, and healthy controls (CA, n=52; AA, n=45). Results: SPARC antigen levels in the sera showed a difference in the overall case versus control groups (p=0.0016) and this trend was observed only in AA (p=0.0015) in comparison to CA patients (p=0.1709). SPARC AAbs were detected in the sera and the values were significant in the overall case versus control (p&amp;lt; .0001) and also in CA (p&amp;lt;.0001) and AA (p&amp;lt;.0001) CaP patients with levels significantly lower in patients compared to controls. AAb reactivity for CaP patients was similar between CA and AA groups. Conclusions: This study demonstrated the presence of AAbs against SPARC in CaP patient serum for the first time. Of note, highly significant differences were noted between CaP patient (low) and controls (high) sera, across different ethnic groups. These data suggest further evaluation of SPARC AAbs as a promising serum biomarker for CaP. Source of Funding: This research was supported by the Center for Prostate Disease Research, Uniformed Services University Grant HU0001-10-2-0002. Citation Format: Anshu Rastogi, Andy Martinez, Amina Ali, Shyh-Han Tan, Jennifer Cullen, Yongmei Chen, Gyorgy Petrovics, Albert Dobi, Lakshmi Ravindranath, Denise Young, Isabell Sesterhenn, Jacob Kagan, Sudhir Srivastava, David McLeod, Inger Rosner, Shiv Srivastava, Alagarsamy Srinivasan. Secreted protein acidic and rich in cysteine antigen and autoantibodies in sera of prostate cancer patients: Potential use in diagnosis /prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2830. doi:10.1158/1538-7445.AM2017-2830

AB0493 Association between antiviral igm antibodies and myositis autoantibodies in patients with autoimmune myositis in bulgarian population

BackgroundConsiderable evidences indicate that the viruses may be important environmental factors in the pathogenesis of the connective tissue diseases – systemic lupus erythematodes, systemic sclerosis, myositis, etc.1 Viruses activate a...

Microstructure and thermal degradation of poly(ether ketone sulfone) copolymers: 13C NMR and thermogravimetry studies

Microstructure of poly(ether ketone sulfone) copolymers I–V, derived from varying mol proportions of dihydroxy diphenyl sulfone (DHDPS, A) and dihydroxybenzophenone (DHBP, C) with stochiometric amounts of difluorobenzophenone (DFBP, B) was studied by 13C nuclear magnetic resonance spectroscopy. The results were interpreted in terms of the compositional triads BBB, BBA, ABA, BAB, and AAB because B and C moieties become indistinguishable in the copolymers. Feed ratios calculated from the triad intensities agree well with experimental values, validating the chemical shift assignments. The presence of AAB and BBA triads in polymer II (A : C = 1 : 0) indicates the occurrence of transetherification reaction during its synthesis. Thermal decomposition characteristics of the copolymers were studied by thermogravimetry. Activation energies for thermal degradation were calculated using Coats-Redfern's method assuming the order of the reaction is 1 and was found to vary from 281 to 193 kJ mol−1. A good linear correlation was obtained between activation energy values and BBB triad intensities. These observations were rationalized by consideration of their decomposition mechanisms. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3425–3431, 1999

Microstructure and thermal degradation of poly(ether ketone sulfone) copolymers:13C NMR and thermogravimetry studies

Microstructure of poly(ether ketone sulfone) copolymers I–V, derived from varying mol proportions of dihydroxy diphenyl sulfone (DHDPS, A) and dihydroxybenzophenone (DHBP, C) with stochiometric amounts of difluorobenzophenone (DFBP, B) was studied by 13C nuclear magnetic resonance spectroscopy. The results were interpreted in terms of the compositional triads BBB, BBA, ABA, BAB, and AAB because B and C moieties become indistinguishable in the copolymers. Feed ratios calculated from the triad intensities agree well with experimental values, validating the chemical shift assignments. The presence of AAB and BBA triads in polymer II (A : C = 1 : 0) indicates the occurrence of transetherification reaction during its synthesis. Thermal decomposition characteristics of the copolymers were studied by thermogravimetry. Activation energies for thermal degradation were calculated using Coats-Redfern's method assuming the order of the reaction is 1 and was found to vary from 281 to 193 kJ mol−1. A good linear correlation was obtained between activation energy values and BBB triad intensities. These observations were rationalized by consideration of their decomposition mechanisms. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3425–3431, 1999

Investigation of autoantibodies directed against tissue-specific myocardial antigens in dilated cardiomyopathy

The autoantibodies directed against actin and myosine have been detected in the blood sera of patients with dilated cardiomyopathy (DCMP) at the level that was sufficiently higher than in healthy donors. While comparing of the immunogeneicity of these pro­ teins we have stated that myosine from affected by DCMP myocardium have been more immunogenic then from normal one. In the case of actin the immunogeneicity have been higher for the protein from normal myocard. The investigations of actin by limited proteolysis may suggest that the differencies in immune properties are not connected with primary structure but with structures of higher levels. Introduction. Nowadays the presence of autoimmune processes during the development of various pathologies including heart diseases is obvi­ ous. At the same time the functional activity of autoAbs wasn't exami­ ned enough. The investigation of structural and functional properties of autoantibodies (aAbs) directed against antigens from heart and vessels, the establishment of their role while the origin and development of heart diseases is necessary not only for theoretical but for practical aims also, in the context of developing of novel therapeutic and diagnostic prepa­ rations (1). The aim of our investigation was to study the molecular mechanisms of autoantibodyg enesis directed against the most important tissue-speci­ fic antigens — actin and myosin, during development of dilated cardio­ myopathy (DCMP). In recent studies the aAbs directed against adenine nucleotide translocator (ANT) (2), the mitochondrial enzyme from myo­ cytes were detected; the aAbs directed against another mitochondrial en­ zyme, branched chain keto acid dehydrogenase (BCKD) (3) were also described at DCMP and myocarditis. The laboratory of Limas (USA) during recent years studied the structure and properties of aAbs directed against p-adrenoreceptor (4—8); these aAbs were detected in 30—40 % of patients with DCMP. The presence of aAbs directed against myosin, tropomyosin, vimentin, laminin at some heart diseases such as postmyo- cardial infarction syndrome, dilated cardiomyopathy, infectious myocar­ ditis, and doxorubicin (Adriamycin) cardiotoxicity (9)' is occasionally accompanied by the deposition of antibodies within the myocardium, par­ ticularly on the sarcolemma. The present paper is a first stage of study of aAbs, their properties and role at DCMP progressing, which are directed against the most abundant heart antigens — actin and myosin. The method described (10) for purifing of preparative quantities of antigens from human myocardium (pathomorphological material) enabled us to obtain the mentioned above antigens as from normal myocardium as from myocardium, affected by DCMP. The presence of aAbs in the sera of patients with DCMP was not unexpected because many facts suggested the presence of cellular and humoral immunity in the development of DCMP {4). These data concern © L. L. Sidorik, N. V. Rodnin, V. I. Bobyk, D. V. Ryabenko, A. V, Veberov, T. Yu. Tkachenko G. Kh. Matsuka, 1996