MHV68 Infection in a Novel rag2 F62L/F62L Mouse Model Based on a Patient with CID-G/AI Phenotype
Poster Feb 27, 2017
Csomos K, Ujhazi B, Stoltz K, Ijspeert H, Mei Yan, Quan-Zhen Li, Csizmadia E, Butte MJ, Coppola D, van der Burg M, Tarakanova V, Walter JE
Objective: Immunodeficiencies secondary to partial RAG1/2 mutations have a widening autoimmune clinical spectrum and autoantibodies, including those targeting cytokines. Herpes virus infections are often observed prior to the onset of autoimmunity.
Methods: To study this phenomenon, a novel murine model was designed with rag2F62L/F62L (mut/mut) modeling a patient with partial Rag deficiency (19.6% Rag2 recombinase activity), history of autoimmune cytopenia and complicated herpes virus infection. Mice were infected with mouse gammaherpesvirus-68 (MHV-68) and cellular and humoral response were monitored. B cell tolerance checkpoints were examined.
Results: At baseline mut/mut mice had increased use of proximal IgH J genes consistent with partial Rag activity. Although viral latency was comparable, antibody generation to virus and self-antigens were increased and larger lymphoid infiltrates (lung, liver, kidney) were noted in mut/mut versus wt/wt mice (p<0.05). Receptor editing in bone marrow Fraction D B cells, serum B cell activating factor (BAFF) levels and regulatory T compartments did not differ significantly.
Conclusions: MHV-68 infection in our rag2 mouse model induced increased antibody responses to virus and self and inflammatory disease in end organs. Major mechanism of inflammatory infiltrates and autoantibody generation is yet to be determined
Characterization of a Type 2 diabetes-associated islet-specific enhancer cluster in STARD10 by genome editing of EndoC-βH1 cellsPoster
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
Treatment Options for Chronic Parvovirus Viremia in Pediatric Heart Transplant Patients in a Tertiary Care CenterPoster
This abstract discusses three cases of pediatric heart transplant patients who suffered from parvovirus (B19) infection. Of these patients, two ( B & C) responded well to standard intravenous Ig therapy. Patient A however, did not respond to standard treatment and was begun on subcutaneous Ig, which effectively diminished his viral load. Thus, subcutaneous Ig infusions might serve as a second line treatment for transplant patients with parvovirus who do not respond well to the standard approach.READ MORE
T-helper cell phenotype expression in cutaneous lesions of angioimmunoblastic T-cell lymphomaPoster
Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. Our case highlights the extranodal presentation of AITL with cutaneous lesions displaying the TFH phenotype.READ MORE
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