scholarly journals The Anti-DNA Antibodies: Their Specificities for Unique DNA Structures and Their Unresolved Clinical Impact—A System Criticism and a Hypothesis

2022 ◽  
Vol 12 ◽  
Author(s):  
Ole Petter Rekvig

Systemic lupus erythematosus (SLE) is diagnosed and classified by criteria, or by experience, intuition and traditions, and not by scientifically well-defined etiology(ies) or pathogenicity(ies). One central criterion and diagnostic factor is founded on theoretical and analytical approaches based on our imperfect definition of the term “The anti-dsDNA antibody”. “The anti-dsDNA antibody” holds an archaic position in SLE as a unique classification criterium and pathogenic factor. In a wider sense, antibodies to unique transcriptionally active or silent DNA structures and chromatin components may have individual and profound nephritogenic impact although not considered yet – not in theoretical nor in descriptive or experimental contexts. This hypothesis is contemplated here. In this analysis, our state-of-the-art conception of these antibodies is probed and found too deficient with respect to their origin, structural DNA specificities and clinical/pathogenic impact. Discoveries of DNA structures and functions started with Miescher’s Nuclein (1871), via Chargaff, Franklin, Watson and Crick, and continues today. The discoveries have left us with a DNA helix that presents distinct structures expressing unique operations of DNA. All structures are proven immunogenic! Unique autoimmune antibodies are described against e.g. ssDNA, elongated B DNA, bent B DNA, Z DNA, cruciform DNA, or individual components of chromatin. In light of the massive scientific interest in anti-DNA antibodies over decades, it is an unexpected observation that the spectrum of DNA structures has been known for decades without being implemented in clinical immunology. This leads consequently to a critical analysis of historical and contemporary evidence-based data and of ignored and one-dimensional contexts and hypotheses: i.e. “one antibody - one disease”. In this study radical viewpoints on the impact of DNA and chromatin immunity/autoimmunity are considered and discussed in context of the pathogenesis of lupus nephritis.

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jiali Zhu ◽  
Kui Cui ◽  
Jianqun Kou ◽  
Shuzhi Wang ◽  
Yinli Xu ◽  
...  

Systemic lupus erythematosus (SLE) is an autoimmune disease and effective therapy for this pathology is currently unavailable. We previously reported that oral administration ofNaja naja atravenom (NNAV) had anti-inflammatory and immune regulatory actions. We speculated that NNAV may have therapeutic effects in MRL/lpr SLE mice. Twelve-week-old MRL/lpr mice received oral administration of NNAV (20, 40, and 80 μg/kg) orTripterygium wilfordii polyglycosidium(10 mg/kg) daily for 16 weeks. The effects of NNAV on SLE manifestations, including skin erythema, proteinuria, and anxiety-like behaviors, were assessed with visual inspection and Multistix 8 SG strips and open field test, respectively. The pathology of spleen and kidney was examined with H&E staining. The changes in autoimmune antibodies and cytokines were determined with ELISA kits. The results showed that NNAV protected against the manifestation of SLE, including skin erythema and proteinuria. In addition, although no apparent histological change was found in liver and heart in MRL/lpr SLE mice, NNAV reduced the levels of glutamate pyruvate transaminase and creatine kinase. Furthermore, NNAV increased serum C3 and reduced concentrations of circulating globulin, anti-dsDNA antibody, and inflammatory cytokines IL-6 and TNF-α. NNAV also reduced lymphadenopathy and renal injury. These results suggest that NNAV may have therapeutic values in the treatment of SLE by inhibiting autoimmune responses.


EDUKASI ◽  
2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Hendra Karianga

Sources of revenue and expenditure of APBD (regional budget) can be allocated to finance the compulsory affairs and optional affairs in the form of programs and activities related to the improvement of public services, job creation, poverty alleviation, improvement of environmental quality, and regional economic growth. The implications of these policies is the need for funds to finance the implementation of the functions, that have become regional authority, is also increasing. In practice, regional financial management still poses a complicated issue because the regional head are reluctant to release pro-people regional budget policy, even implication of regional autonomy is likely to give birth to little kings in region causing losses to state finance and most end up in legal proceedings. This paper discusses the loss of state finance and forms of liability for losses to the state finance. The result of the study can be concluded firstly,  there are still many differences in giving meaning and definition of the loss of state finace and no standard definition of state losses, can cause difficulties. The difficulty there is in an effort to determine the amount of the state finance losses. The calculation of state/regions losses that occur today is simply assessing the suitability of the size of the budget and expenditure without considering profits earned by the community and the impact of the use of budget to the community. Secondly, the liability for losses to the state finance is the fulfillment of the consequences for a person to give or to do something in the regional financial management by giving birth to three forms of liability, namely the Criminal liability, Civil liability, and Administrative liability.Keywords: state finance losses, liability, regional finance.


2017 ◽  
Vol 3 (2) ◽  
pp. 7
Author(s):  
Saida Parvin

Women’s empowerment has been at the centre of research focus for many decades. Extant literature examined the process, outcome and various challenges. Some claimed substantial success, while others contradicted with evidence of failure. But the success remains a matter of debate due to lack of empirical evidence of actual empowerment of women around the world. The current study aimed to address this gap by taking a case study method. The study critically evaluates 20 cases carefully sampled to include representatives from the entire country of Bangladesh. The study demonstrates popular beliefs about microfinance often misguide even the borrowers and they start living in a fabricated feeling of empowerment, facing real challenges to achieve true empowerment in their lives. The impact of this finding is twofold; firstly there is a theoretical contribution, where the definition of women’s empowerment is proposed to be revisited considering findings from these cases. And lastly, the policy makers at governmental and non-governmental organisations, and multinational donor agencies need to revise their assessment tools for funding.


2019 ◽  
Vol 67 (6) ◽  
pp. 483-492
Author(s):  
Seonghyeon Baek ◽  
Iljae Lee

The effects of leakage and blockage on the acoustic performance of particle filters have been examined by using one-dimensional acoustic analysis and experimental methods. First, the transfer matrix of a filter system connected to inlet and outlet pipes with conical sections is measured using a two-load method. Then, the transfer matrix of a particle filter only is extracted from the experiments by applying inverse matrices of the conical sections. In the analytical approaches, the one-dimensional acoustic model for the leakage between the filter and the housing is developed. The predicted transmission loss shows a good agreement with the experimental results. Compared to the baseline, the leakage between the filter and housing increases transmission loss at a certain frequency and its harmonics. In addition, the transmission loss for the system with a partially blocked filter is measured. The blockage of the filter also increases the transmission loss at higher frequencies. For the simplicity of experiments to identify the leakage and blockage, the reflection coefficients at the inlet of the filter system have been measured using two different downstream conditions: open pipe and highly absorptive terminations. The experiments show that with highly absorptive terminations, it is easier to see the difference between the baseline and the defects.


2020 ◽  
Vol 13 (1) ◽  
pp. e229382
Author(s):  
Tiago Gama Ramires ◽  
Luísa Vieira ◽  
Nuno Riso ◽  
Maria Francisca Moraes-Fontes

A 23-year-old woman with fever, oral ulcers, arthalgias and weight loss of 2-week duration suddenly developed blurred vision, with reduced visual acuity, cotton wool exudates and retinal vascular tortuosity. Laboratory testing revealed anaemia, lymphopaenia, positive antinuclear antibody and high anti-dsDNA antibody titre with low complement components. There was no evidence of infection, clinching the diagnosis of lupus retinopathy. Steroid therapy alone was highly effective and was also accompanied by a normalisation of haemoglobin and lymphocyte counts, after which azathioprine was added. Hydroxychloroquine was introduced after resolution of retinal changes. Immunosuppressive therapy was progressively tapered over the course of 12 months and then discontinued, and the patient remains in remission 48 months after the initial presentation. Our patient exemplifies a very rare manifestation of systemic lupus erythematosus. We emphasise the importance of its early detection and complexity of treatment in order to reduce visual morbidity.


2021 ◽  
pp. 101053952110260
Author(s):  
Mairead Connolly ◽  
Laura Phung ◽  
Elise Farrington ◽  
Michelle J. L. Scoullar ◽  
Alyce N. Wilson ◽  
...  

Preterm birth and stillbirth are important global perinatal health indicators. Definitions of these indicators can differ between countries, affecting comparability of preterm birth and stillbirth rates across countries. This study aimed to document national-level adherence to World Health Organization (WHO) definitions of preterm birth and stillbirth in the WHO Western Pacific region. A systematic search of government health websites and 4 electronic databases was conducted. Any official report or published study describing the national definition of preterm birth or stillbirth published between 2000 and 2020 was eligible for inclusion. A total of 58 data sources from 21 countries were identified. There was considerable variation in how preterm birth and stillbirth was defined across the region. The most frequently used lower gestational age threshold for viability of preterm birth was 28 weeks gestation (range 20-28 weeks), and stillbirth was most frequently classified from 20 weeks gestation (range 12-28 weeks). High-income countries more frequently used earlier gestational ages for preterm birth and stillbirth compared with low- to middle-income countries. The findings highlight the importance of clear, standardized, internationally comparable definitions for perinatal indicators. Further research is needed to determine the impact on regional preterm birth and stillbirth rates.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.


Sign in / Sign up

Export Citation Format

Share Document