Monitoring Autoimmune Reactivity within the Retina

Author(s):  
John J. Hooks ◽  
Chi-Chao Chan ◽  
H. Nida Sen ◽  
Robert Nussenblatt ◽  
Barbara Detrick
Author(s):  
U Hardt ◽  
A Larsson ◽  
I Gunnarsson ◽  
GJ Silverman ◽  
E Svenungsson ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Elias Blasius ◽  
Elke Gülden ◽  
Hubert Kolb ◽  
Christiane Habich ◽  
Volker Burkart

Background. Heat shock proteins (Hsp) act as intracellular chaperones and in addition are used as adjuvant in vaccines of peptides complexed with recombinant Hsp. By interacting with autologous peptides, Hsp may promote the induction of autoimmune reactivity. Objective. Here, we analysed whether the effect of Hsp on macrophages is modulated by insulin peptides known to interact with Hsp. Results. Combinations of the 70 kDa Hsp DnaK with peptide B11-23 from the core region of the proinsulin B-chain induced the release of the inflammatory mediators interleukin-6, tumor necrosis factor α, and interleukin-1β from cells of human and murine macrophage lines. In parallel, there was high-affinity binding of B11-23 to DnaK. DnaK mixed with peptides from other regions of the insulin molecule did not stimulate cytokine secretion. DnaK alone induced little cytokine production, and peptides alone induced none. Conclusion. The macrophage-stimulating potential of Hsp70 family proteins when combined with the proinsulin B-chain peptide B11-23 may contribute to the immunodominance of this peptide in the development of beta cell-directed autoimmunity in type 1 diabetes.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 489-489
Author(s):  
Nicoletta Sorvillo ◽  
Simon D. van Haren ◽  
Paul H. Kaijen ◽  
Anja ten Brinke ◽  
Rob Fijnheer ◽  
...  

Abstract Abstract 489 Autoantibodies directed against ADAMTS13 prohibit the processing of VWF multimers initiating a rare and life-threatening disorder called acquired thrombotic thrombocytopenic purpura (TTP). Recently, HLA-DRB1*11 has been identified as a risk factor for the development of acquired TTP. Here, we identified ADAMTS13-derived peptides presented on MHC class II alleles. Dendritic cells from a panel of both HLA-DRB1*11 positive and negative donors were pulsed with ADAMTS13 and the HLA-DR-presented peptide repertoire was analyzed by mass spectrometry. Interestingly, pulsing of dendritic cells of HLA-DRB1*11 positive donors with 100 nM ADAMTS13 resulted in presentation of a single CUB2 derived ADAMTS13 peptide. This peptide was not presented by HLA-DRB1*11 negative donors. Pulsing of HLA-DRB1*0301 positive cells with 100 nM ADAMTS13 resulted in presentation of a different CUB2 domain derived peptide in 2 out of 3 donors analyzed. Pulsing of dendritic cells employing higher concentrations of ADAMTS13 (500 nM) resulted in increased presentation of ADAMTS13 derived peptides by both HLA-DRB1*11 positive and negative donors. In DRB1*11 negative donors peptides derived of multiple domains were presented which included spacer, TSR2-8, metalloprotease and disintegrin domains. Interestingly, the CUB2 domain peptide (specific for DRB1*11 when dendritic cells were pulsed with 100 nM ADAMTS13) was also presented under these conditions. Apparently, this peptide can be presented by multiple MHC class II alleles although higher concentrations of ADAMTS13 are required for its presentation on DCs derived of non-DRB1*11 positive donors. Interestingly, the diversity of ADAMTS13 derived peptides presented by iDCs of donors HLA-DRB1*11 was not affected by pulsing of iDCs with higher concentration of ADAMTS13. Also, under these conditions the only peptides that were presented were derivatives of the CUB2 domain derived peptide that was also presented at lower concentrations of ADAMTS13. Our results clearly demonstrate that this peptide is efficiently presented when compared to other ADAMTS13-derived peptides. Therefore, we hypothesize that efficient presentation of this CUB2 domain derived peptide on DRB1*11 may provoke proliferation of low affinity self-reactive CD4+ T cells that have escaped negative selection in the thymus and contribute to the onset of acquired TTP. Together these findings may provide further insight in the initiation of the autoimmune reactivity against ADAMTS13 in patients affected by TTP. Disclosures: No relevant conflicts of interest to declare.


2000 ◽  
Vol 35 (3) ◽  
pp. 226-234 ◽  
Author(s):  
Isao Matsuo ◽  
Nobuhiro Ikuno ◽  
Katsuhisa Omagari ◽  
Hideki Kinoshita ◽  
Mikio Oka ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Aristo Vojdani

Autoimmune diseases have registered an alarming rise worldwide in recent years. Accumulated evidence indicates that the immune system's ability to distinguish self from nonself is negatively impacted by genetic factors and environmental triggers. Genetics is certainly a factor, but since it normally takes a very long time for the human genetic pattern to change enough to register on a worldwide scale, increasingly the attention of studies has been focused on the environmental factors of a rapidly changing and evolving civilization. New technology, new industries, new inventions, new chemicals and drugs, and new foods and diets are constantly and rapidly being introduced in this fast-paced ever-changing world. Toxicants, infections, epitope spreading, dysfunctions of immune homeostasis, and dietary components can all have an impact on the body's delicate immune recognition system. Although the precise etiology and pathogenesis of many autoimmune diseases are still unknown, it would appear from the collated studies that there are common mechanisms in the immunopathogenesis of multiple autoimmune reactivities. Of particular interest is the citrullination of host proteins and their conversion to autoantigens by the aforementioned environmental triggers. The identification of these specific triggers of autoimmune reactivity is essential then for the development of new therapies for autoimmune diseases.


2015 ◽  
Vol 2 (3) ◽  
pp. 211-221 ◽  
Author(s):  
Vrushali V. Agashe ◽  
William J. Burlingham

2021 ◽  
Author(s):  
Yunxian Liu ◽  
Joseph E. Ebinger ◽  
Rowann Mostafa ◽  
Petra Budde ◽  
Jana Gajewski ◽  
...  

Background. Amidst the millions of individuals affected directly by the pandemic, pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating not only the acute response but also recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, we deliberately examined sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease. Methods. We used a bead-based array containing over 90 autoantigens previously linked to a range of classic autoimmune diseases to assess autoantibody (AAB) titers in 177 participants. All participants had confirmed evidence of prior SARS-CoV-2 infection based on presence of positive anti-nucleocapsid IgG serology results (Abbott Diagnostics, Abbott Park, Illinois). We used multivariate analysis to determine whether sex-bias was associated with increased rates of AABs reactivity and symptom burden after SARS-CoV2 infection. Results. 82.4% of AABs reactivity was associated with being male compared to 17.6% with female. We found a diversity of AABs responses that exhibited sex-specific patterns of frequency distribution as well as associations with symptomatology and symptom burden. Conclusion. Our results reveal a remarkable sex-specific prevalence and selectivity of AAB responses to SARS-CoV-2. Further understanding of the nature of triggered and persistent AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.


JAMA ◽  
1981 ◽  
Vol 246 (7) ◽  
pp. 763-765 ◽  
Author(s):  
R. A. Sturner

Sign in / Sign up

Export Citation Format

Share Document