A Wideband ADI-FDTD Algorithm for the Design of Double Negative Metamaterial-BasedWaveguides and Antenna Substrates

Background:Rituximab (RTX) is a chimeric monoclonal antibody against CD20. There is a paucity of studies done with RTX biosimilars. This is a Retrospective and Observational study from January 2018 to December 2019 done in the Department of Clinical Immunology & Rheumatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.Objectives:1.To find the effects of varying doses of RTX in attaining clinical remission in RA.2.To find if CD19, CD20 & IgG help in identifying impending flare & if these levels help in deciding the timing of the next dose of RTX.Methods:Rheumatoid arthritis (RA) cases who were given Rituximab from January 2018 were selected. Clinical Response at 6 & 12 months & wherever feasible at 18 & 24 months was assessed by Simplified Disease Activity index (SDAI). RTX initial dose was given at 0 and 14 days followed by fixed dose at six months interval.CD19, CD20 B cell count, IgG levels were tested in patients in whom it was feasible at baseline & 6 months (select patients at 12,18 &24 months). Patients were divided in to 5 groups (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and (500mg & 1g). Patients were divided into three clinical groups, (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and two treatment groups (500mg & 1g) based on clinical indication for RTX and dose of RTX, respectively. In patients with ILD, CT scan & FVC were compared at baseline & 12 months.Results:29 patients (seropositive 28 (RF/Anti CCP/BOTH+VE), seronegative 1) were given RTX for RA over a 2-year period of which 12 had CD19, CD20 & IgG tested. Mean SDAI reduction from baseline to 6 months post treatment was 30%, 32% & 14% while complete remission (SDAI<3.3) was attained in 100%, 18% & 20% in DMARD naïve, DMARD resistant & ILD groups, respectively. CD19, CD20 & IgG reduced from 18.6%, 18.4% & 18.53g/L to 3.7%,3.7% & 9.7g/L respectively FVC improved from 62.4% to 67% at 12. The percentage of patients with lung involvement >20% reduced from 53.3% to 46.7%. Flare was observed in one patient who received 500mg RTX. CD19, CD20 & IgG levels increased from 7.9%, 8% & 9.8g/L to 27%, 25% & 13g/L respectively. 3 patients in the 1g group were followed up at 12,18 & 24 months. In these patients there were no flares or worsening symptoms. 1 patient was double negative for RF & Anti CCP and this patient did not attain clinical remission even after 2 doses of 1g RTX.Conclusion:[1]Patients with early arthritis (diagnosis made within 1 year) and who were DMARD naïve had an excellent response to Rituximab.[2]Complete remission was observed in more patients the 1g compared to 500mg group.[3]Reduction in CD19 & CD20 was associated with significant reduction in the SDAI score.[4]There was no significant reduction of CD19 & CD20 with 500mg dose of Rituximab where either a partial remission or mild flare was observed.[5]There was reduction in the lung involvement to less than 20%(CT) in few patients with 1g dose.[6]Double negative Rheumatoid arthritis poorly responded to Rituximab.[7]The positive effects of 1g Rituximab could be noted up to 24 months.[8]Flare of RA was associated with significant increase in CD19 & CD20.Disclosure of Interests:None declared

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Frontotemporal Dementia with Parkinsonism and Epilepsy Associated with VGKC Antibodies: Case Report and Literature Review

Case Reports in Neurology ◽

10.1159/000513852 ◽

2021 ◽

pp. 205-210

Author(s):

Matthew Saint ◽

Vafa Alakbarzade ◽

Brendan McLean

Keyword(s):

Case Report ◽

Literature Review ◽

Frontotemporal Dementia ◽

Limbic Encephalitis ◽

Poor Response ◽

Double Negative ◽

Aggressive Treatment ◽

Voltage Gated ◽

Negative Results ◽

Autoimmune Conditions

Antibodies directed against the voltage-gated potassium channel complex (anti-VGKCs) are implicated in several autoimmune conditions including limbic encephalitis and epilepsy. However, emerging evidence suggests that only specific subtypes of anti-VGKCs are pathogenic. We present the case of a 55-year-old man who initially presented with focal unaware seizures and behavioural changes mimicking anti-VGKC-seropositive encephalitis that further progressed to parkinsonism with evidence of frontotemporal dementia and pre-synaptic dopaminergic deficit. Aggressive treatment with immunotherapy was ineffective, and antibody subtyping later revealed the anti-VGKC antibodies to be negative for leucine-rich glioma-associated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) – the two known pathogenic subtypes. The clinical relevance of so-called “double-negative” anti-VGKCs (i.e., those not directed towards LGI1 or CASPR2) has been called into question in recent years, with evidence to suggest they may be clinically insignificant. Our case emphasises the importance of antibody subtyping in cases of anti-VGKC seropositivity; negative results, particularly when combined with a poor response to immunotherapy, should prompt a rapid reconsideration of the working diagnosis.

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Trafficking phenotype and production of granzyme B by double negative B cells (IgG+IgD−CD27−) in the elderly

Experimental Gerontology ◽

10.1016/j.exger.2013.12.011 ◽

2014 ◽

Vol 54 ◽

pp. 123-129 ◽

Cited By ~ 26

Author(s):

Matteo Bulati ◽

Silvio Buffa ◽

Adriana Martorana ◽

Giuseppina Candore ◽

Domenico Lio ◽

...

Keyword(s):

B Cells ◽

Granzyme B ◽

The Elderly ◽

Double Negative

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Double-negative T cells are absolutely elevated in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis

Molecular Immunology ◽

10.1016/j.molimm.2021.01.014 ◽

2021 ◽

Author(s):

Yan Qin ◽

Yanlin Wang ◽

Yanyao Wu ◽

Min Feng ◽

Xiangcong Zhao ◽

...

Keyword(s):

T Cells ◽

Double Negative ◽

Antineutrophil Cytoplasmic Autoantibody ◽

Double Negative T Cells

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Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22010274 ◽

2020 ◽

Vol 22 (1) ◽

pp. 274

Author(s):

Claudia Curci ◽

Angela Picerno ◽

Nada Chaoul ◽

Alessandra Stasi ◽

Giuseppe De Palma ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Progenitor Cells ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Double Negative ◽

Chronic Injury ◽

Peripheral Blood Mononuclear ◽

Cell Subpopulations ◽

T Cell Subpopulations

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8+ and CD4+ T cells. Instead, Tregs and CD3+ CD4- CD8- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.

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