scholarly journals DNA-hydrolysing activity of IgG antibodies from the sera of patients with schizophrenia

Open Biology ◽  
2015 ◽  
Vol 5 (9) ◽  
pp. 150064 ◽  
Author(s):  
Evgeny A. Ermakov ◽  
Ludmila P. Smirnova ◽  
Taisiya A. Parkhomenko ◽  
Pavel S. Dmitrenok ◽  
Nina M. Krotenko ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Mass Spectra ◽  
Intrinsic Property ◽  
Dnase Activity ◽  
Light Chains ◽  
Double Stranded Dna ◽  
Healthy Donors ◽  
Lower Molecular Mass ◽  
Autoimmune Processes ◽  
Dna Antibodies

It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self-antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmune systemic lupus erythematosus (SLE) patients, two maxima of a comparable intensity. In addition, the MALDI spectra of the IgG light chains of five SLE and four SCZ patients contained a small additional brightly pronounced peak with remarkably lower molecular mass compared with the main one. DNase autoantibodies (abzymes) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases without a significant disturbance of the immune status does not contain DNase abzymes. Here, we present the first analysis of anti-DNA antibodies and DNase abzymes in the sera of SCZ patients. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of SCZ patients. The sera of approximately 30% of SCZ patients displayed a higher content of antibodies (compared with 37% of SLE) interacting with single- and double-stranded DNA compared with healthy donors. Antibodies with DNase activity were revealed in 80% of the patients. These data indicate that some SCZ patients may show signs of typical autoimmune processes to a certain extent.

scholarly journals Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

2005 ◽  
Vol 52 (4) ◽  
pp. 1129-1137 ◽  
Author(s):  
Matthew D. Linnik ◽  
Jay Z. Hu ◽  
Kenneth R. Heilbrunn ◽  
Vibeke Strand ◽  
Frank L. Hurley ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Dna Antibodies

scholarly journals Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Guang-ping Ruan ◽  
Xiang Yao ◽  
Shuang-juan Yang ◽  
Jin-xiang Wang ◽  
Fan Shu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Umbilical Cord ◽  
Lupus Erythematosus ◽  
Human Umbilical Cord ◽  
Systemic Lupus ◽  
Multisystem Disease ◽  
Double Stranded Dna ◽  
Dna Antibodies ◽  
Disease Indicators

Background. Systemic lupus erythematosus (SLE) is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists.Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC) transplantation to treat B6.Fas mice.Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation.Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

scholarly journals Tick-borne encephalitis: immunological indicators of possible transformation of acute process into chronic disease

2010 ◽  
Vol 9 (4) ◽  
pp. 5-18
Author(s):  
Ye. I. Gusev ◽  
T. A. Parkhomenko ◽  
V. N. Buneva ◽  
O. B. Doronina ◽  
V. B. Doronin ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Affinity Chromatography ◽  
Clinical Course ◽  
Intrinsic Property ◽  
Relative Activity ◽  
Dnase Activity ◽  
Tick Borne Encephalitis ◽  
Level Of Activity ◽  
Healthy Donors ◽  
Different Levels

Several autoimmune diseases with chronic clinical course are characterized by detection of DNA autoantibodies in patients’ serum, while there are no such IgGs in healthy donors’ blood or in patients with acute clinical course with no evidence of chronization. Tick-borne encephalitis has not been considered this way. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of TBE patients but not from healthy donors. The relative activity of IgGs has been shown to vary extensively from patient to patient, but most of the preparations (91%) had detectable levels of the DNase activity. Polyclonal DNase IgGs were not active in the presence of EDTA or after a dialysis against EDTA, but could be activated by several externally added metal ions, with the level of activity decreasing in the order Mn2+ + Ca2+ ≥ Mn2+ + Mg2+ ≥ Mn2+ ≥ ≥ Mg2+ + Ca2+ ≥ Ca2+ ≥ Mg2+ > Ca2+, while K+ , Na+ , Ni2+, Zn2+, and Cu2+ did not stimulate DNA hydrolysis. Affinity chromatography on DNA-cellulose separated the DNase IgGs into many subfractions with various affinities for DNA and very different levels of the relative activity. Possible reasons for catalytic diversity of polyclonal human Abzs are discussed.

scholarly journals MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti–double-stranded DNA B Cells

1999 ◽  
Vol 189 (11) ◽  
pp. 1799-1814 ◽  
Author(s):  
Laura Mandik-Nayak ◽  
Su-jean Seo ◽  
Caroline Sokol ◽  
Kathryn M. Potts ◽  
Anh Bui ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Genetic Background ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Developmental Arrest ◽  
Double Stranded Dna ◽  
Dna Antibodies ◽  
Cell Defect

A hallmark of systemic lupus erythematosus and the MRL murine model for lupus is the presence of anti–double-stranded (ds)DNA antibodies (Abs). To identify the steps leading to the production of these Abs in autoimmune mice, we have compared the phenotype and localization of anti-dsDNA B cells in autoimmune (MRL+/+ and lpr/lpr) mice with that in nonautoimmune (BALB/c) mice. Anti-dsDNA B cells are actively regulated in BALB/c mice as indicated by their developmental arrest and accumulation at the T–B interface of the splenic follicle. In the MRL genetic background, anti-dsDNA B cells are no longer developmentally arrested, suggesting an intrinsic B cell defect conferred by MRL background genes. With intact Fas, they continue to exhibit follicular exclusion; however, in the presence of the lpr/lpr mutation, anti-dsDNA B cells are now present in the follicle. Coincident with the altered localization of anti-dsDNA B cells is a follicular infiltration of CD4 T cells. Together, these data suggest that MRL mice are defective in maintaining the developmental arrest of autoreactive B cells and indicate a role for Fas in restricting entry into the follicle.

scholarly journals Regulation of Anti–double-stranded DNA B Cells in Nonautoimmune Mice: Localization to the T–B Interface of the Splenic Follicle

1997 ◽  
Vol 186 (8) ◽  
pp. 1257-1267 ◽  
Author(s):  
Laura Mandik-Nayak ◽  
Anh Bui ◽  
Hooman Noorchashm ◽  
Ashlyn Eaton ◽  
Jan Erikson
Keyword(s):  
B Cells ◽  
Lupus Erythematosus ◽  
Turnover Rate ◽  
Cell Repertoire ◽  
Developmental Arrest ◽  
Double Stranded Dna ◽  
B Cell Repertoire ◽  
Dna Antibodies ◽  
Unique Surface

Systemic lupus erythematosus (SLE) and the MRL-lpr/lpr murine model for SLE are characterized by the presence of serum anti–double-stranded (ds)DNA antibodies (Abs), whereas nonautoimmune individuals have negligible levels of these Abs. To increase the frequency of anti-DNA B cells and identify the mechanisms involved in their regulation in nonautoimmune mice, we have used Ig transgenes (tgs). In the present study, we used the VH3H9 heavy (H) chain tg which expresses an H chain that was repeatedly isolated from anti-dsDNA Abs from MRL-lpr/lpr mice. Because the VH3H9 H chain can pair with endogenous L chains to generate anti–single-stranded DNA, anti-dsDNA, and non-DNA B cells, this allowed us to study the regulation of anti-dsDNA B cells in the context of a diverse B cell repertoire. We have identified anti-dsDNA B cells that are located at the T–B interface in the splenic follicle where they have an increased in vivo turnover rate. These anti-dsDNA B cells exhibit a unique surface phenotype suggesting developmental arrest due to antigen exposure.

scholarly journals Lepromatous leprosy mimicking systemic lupus erithematosus: a case report

2019 ◽  
Vol 28 (1) ◽  
pp. 77-81
Author(s):  
Niken Kusumaningrum ◽  
Schandra Purnamawati ◽  
Dwi Retno Adi Winarni ◽  
Hardyanto Soebono
Keyword(s):  
Lupus Erythematosus ◽  
Correct Diagnosis ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Lepromatous Leprosy ◽  
Test Results ◽  
Systemic Lupus ◽  
Double Stranded Dna ◽  
Morphological Index ◽  
Dna Antibodies

The clinical manifestations of leprosy are highly variable, and the disease is notorious for being “a great imitator” of several other conditions. Leprosy may manifest with a variety of phenomena resembling those of autoimmune diseases. Herein, we report a 33-year-old male presenting with wounds on his left leg and hyperpigmented skin lesions all over his body. Six years earlier, the patient was diagnosed with systemic lupus erythematosus (SLE). However, therapy for SLE did not control his symptoms; instead, the patient developed features of leprosy, such as anesthetic skin lesions, nerve enlargement, and tenderness. Tests for antinuclear antibodies and anti-double stranded DNA antibodies were negative. Slit-skin smear showed a bacterial index of 6+ and morphological index of 10 %. Lupus band test results were negative. Histological findings were compatible with lepromatous leprosy. The clinical and serological similarities between leprosy and SLE may lead to erroneous diagnosis. Thus, clinicians should be aware of this characteristic for correct diagnosis.

The impact of biological treatments on the anti-dsDNA and anti-nucleosome tests

Lupus ◽  
2017 ◽  
Vol 27 (1) ◽  
pp. 40-48 ◽  
Author(s):  
M Infantino ◽  
V Grossi ◽  
M Benucci ◽  
F Li Gobbi ◽  
A Damiani ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Predictive Value ◽  
Inflammatory Arthritis ◽  
Diagnostic Performance ◽  
Systemic Lupus ◽  
Drug Induced ◽  
Dna Test ◽  
Double Stranded Dna ◽  
Dna Antibodies

Background Anti-double stranded DNA antibodies are a very heterogeneous group of antibodies, quite specific for systemic lupus erythematosus. Newer technologies, such as addressable laser bead immunoassays (ALBIA), show great potential as a diagnostic application. The production of anti-double stranded DNA antibodies is often encountered in inflammatory arthritis; however, literature reports that the actual onset of drug induced lupus in patients treated with biological drugs is a rare event. False positive results for anti-double stranded DNA and anti-nucleosome antibodies detected in patients with inflammatory arthritis treated with different biologics prompted the investigation of full autoantibody profiles to evaluate each biomarker’s diagnostic performance in systemic lupus erythematosus. The aim of the study was to compare the diagnostic performance of anti-double stranded DNA antibody and anti-nucleosome antibody methods and to evaluate the value of simultaneously measuring anti-double stranded DNA and anti-nucleosome antibodies, along with other anti-nuclear antibody analytes, as biomarkers for systemic lupus erythematosus, using a more appropriate control cohort including inflammatory arthritis patients with a non-clinical drug induced lupus. Methods Anti-double stranded DNA and anti-nucleosome antibody levels were evaluated in 247 patient samples: 70 systemic lupus erythematosus, 177 disease controls (including 97 inflammatory arthritis during treatment with different biologics) using the Bio-Rad BioPlex® 2200. Results Anti-nucleosome antibodies demonstrated greater clinical sensitivity and specificity than anti-double stranded DNA antibodies. At the manufacturers’ cut-off range, considering the two markers as a single or combined test, the “anti-double stranded DNA test or anti-nucleosome antibodies” was the most sensitive combination (0.400) with the best negative likelihood ratio (0.62) and negative predictive value (0.803). Conclusion Anti-nucleosome antibodies are a more sensitive and specific biomarker of systemic lupus erythematosus than anti-double stranded DNA antibodies. Anti-nucleosome antibodies and anti-double stranded DNA antibodies are independent and complementary markers of systemic lupus erythematosus diagnosis and, therefore, are strongly suggested as combined tests (positive predictive value = 0.938). Moreover, the combined use of the two tests may help to overcome the decreased specificity percentage of the anti-double stranded DNA test, when considering an inflammatory arthritis cohort under biological therapies. The ALBIA method for anti-nuclear specificity detection allows a full autoantibody assessment, resulting in a much higher clinical specificity for systemic lupus erythematosus in the presence of ≥3 positive markers and significantly more positive likelihood ratio when ≥2 positive markers are present.

scholarly journals Mesangial Cell-Specific Antibodies Are Central to the Pathogenesis of Lupus Nephritis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Guillaume Seret ◽  
Yannick Le Meur ◽  
Yves Renaudineau ◽  
Pierre Youinou
Keyword(s):  
Lupus Erythematosus ◽  
Matrix Protein ◽  
Mesangial Cell ◽  
Surface Proteins ◽  
Double Stranded Dna ◽  
Common Complaint ◽  
Life Threatening ◽  
Dna Antibodies ◽  
Chromatin Material ◽  
Immune Complex Formation

Not only is nephritis a common complaint in systemic lupus erythematosus, but it is also the most life-threatening complication of the disease. Anti-double-stranded DNA antibodies (Abs), which are found in up to 80% of these patients, might be nephritogenic per se. That is, they may cross-react with mesangial cell (MC) surface proteins, such as alpha-actinin and annexin A2, they may cross-react with mesangial matrix protein such as laminine and fibronectin, or they may recognize chromatin material previously deposited in the glomeruli. The consequence of the binding of anti-MC Abs may be their internalization, which results in activation and proliferation of these MCs. In turn, these activated MCs are suspected of promoting immune complex formation by sequestering and thereby protecting chromatin from degradation. The present paper will explain the mechanisms through which such autoAbs may initiate nephritis.

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