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    Suppression of Host Humoral Immunity by Borrelia burgdorferi Varies Over the Course of Infection
    (2024-03-21) Williams, Megan; Zhang, Yan; Kilgore, Rebecca; Allen, Michael S.; Berg, Rance E.
    Lyme disease is the most common vector-borne illness in the U.S. with approximately 476,000 cases each year. Borrelia burgdorferi, the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. These strategies include complement inhibition, antigenic variation, and suppression of adaptive immunity. The resulting immune response is characterized by unusually strong IgM production and a lack of long-term protective immunity. Previous studies in mice have shown that infection with B. burgdorferi also broadly suppresses host antibody responses against unrelated antigens. Here we aimed to assess how the host’s ability to produce antibodies against an unrelated antigen may change over the course of infection with B. burgdorferi and whether, if at all, the immune system returns to baseline following antibiotic treatment. Mice infected with B. burgdorferi and concomitantly immunized with recombinant SARS-CoV-2 spike protein had an abrogated antibody response to the immunization. To further define how long this humoral immune suppression lasts, mice were immunized at 2-, 4-, and 6-weeks post-infection. Suppression of host antibody production against the SARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. Antibody responses against the SARS-CoV-2 spike protein were also assessed following antibiotic treatment to determine whether this immune suppression persists or resolves following clearance of B. burgdorferi. Host antibody production against the SARS-CoV-2 spike protein returned to baseline following antibiotic treatment; however, anti-SARS-CoV-2 IgM remained high, comparable to levels found in B. burgdorferi-infected but untreated mice. Thus, our data demonstrate restored IgG responses following antibiotic treatment but persistently elevated IgM levels, indicating lingering effects of B. burgdorferi infection on the immune system following treatment.
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    Investigating an early source of IFN-gamma production post large vessel occlusion in mice
    (2024-03-21) Sharif, Safia; Hernandez, Katherine; Jones, Nathan; Ortega, Sterling
    In the United States, strokes are one of the leading causes of death- with ischemic strokes being the most common. The etiology by which ischemic strokes occur may be due to large vessel occlusion. Typically, this process occurs by which a thrombus or embolus occludes a major vessel within the brain leading to reduced blood flow (ischemia) precipitating damage to brain tissue. Large vessel occlusion is a critical event, in which a rapid response is required to ensure the survival of brain tissue. It is understood that IFN-gamma is involved in the production of various inflammatory mediators, however, in the context of the stroke, it is not known where the IFN-gamma production is sourced from early in the stroke cascade. This study investigates the production of IFN-gamma in the context of a large vessel occlusion in mice. In vitro and in vivo studies were utilized to (1) compare the production of IFN-gamma amongst large vessel pre-occlusion, large vessel post-occlusion, and a distal vascular site (2) examine the direct relationship between oxygen-glucose deprivation applied to mixed cortical cultures and naïve lymphocytes (3) investigate the source of IFN-gamma production. Collected data was analyzed by utilizing flow cytometry. Findings revealed that in comparison to the pre-occlusion, the post-occlusion sample of blood contained increased levels of IFN-gamma. Mixed cortical cultures were examined under ischemic-like conditions and demonstrated increased IFN-gamma production from naïve cells. Evidence also suggested that the most likely source of IFN-gamma production stems from macrophages. IFN-gamma could potentially be an important modulator in the exacerbation of brain parenchymal damage, especially in the context of post-large vessel occlusion.
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    A Rare Case of Anti-NXP2 Antibody Positivity in Juvenile Dermatomyositis – A Case Study
    (2024-03-21) Bosques, Rebeca; Quresh, Quretul
    Background: Dermatomyositis (DM) is one of the many subcategories of Idiopathic Inflammatory Myositis (IIM), a treatable group of myopathies. Antibodies serve as a diagnostic tool with prognostic indicators. DM-specific antibodies include anti-NXP2, anti-MDA5, anti-TIF1gamma, Anti-Mi2, Anti- SAE, and anti-SRP. These DM-specific antibodies are mutually exclusive suggesting the idea that each plays a specific role in shaping different phenotypes. 1-17% of adult DM/ polymyositis (PM) and 23-25% of juvenile dermatomyositis (JDM) present with a positive anti-NXP2 antibody. Clinically, positive anti-NXP2 antibody DM patients present with a rash, debilitating muscle weakness, calcinosis, dysphagia, and a higher risk of malignancy. As compared to patients with negative anti-NXP2 antibody DM, positive anti-NXP2 antibody DM patients were younger at the age of onset, with shorter duration between symptom onset to diagnosis, and no significant sex diseases. The prognosis for positive anti-NXP2 antibody DM depends on the complications developed. The worrisome complications which lead to a poor prognosis are calcinosis and malignancies. Case Information: 22 y/o female was referred to rheumatology for evaluation of Systemic Lupus Erythematosus (SLE). For 3 years prior, the patient experienced muscle and generalized weakness, and myalgia in the legs leading to difficulty climbing stairs. At the time of referral, the patient showed CPK 34, ANA positive anti-dsDNA +12, BUN 15, creatinine 0.70, GFR 123, albumin 4.6, AST 15, ALT 6, ESR 35, WBC 6.5, hemoglobin 10.8, platelets 320. On physical exam, upper and lower extremities showed 4/5 muscle strength. An autoimmune panel to test myositis specific antibodies was ordered. Which showed positive anti-NXP2 21, positive ANA screen IFA, actin antibody (IgG) 34, thyroid peroxidase antibodies 267 IU/mL, ANA titer 1:80. 20 days after, the patient had difficulty getting out of bed with profound generalized weakness. The patient had developed a rash in the upper chest and abdomen. The diagnosis of juvenile dermatomyositis (JDM) was made. Patient admitted to hospital treated with 1 g Methylprednisolone for 3 days and tapered 1 mg/kg body weight. Care with neurology was coordinated to start IVIG treatment at 2 g/kg body weight. The patient was found to have positive acetylcholine receptor antibodies and diagnosed with Myasthenia gravis. The patient was given IVIG for 5 days. The patient was also found to have thyroid nodule swelling s/p biopsy concerning Hurthel cell cancer. On follow-up one month later, the patient stated a return of muscle strength with no rashes. The patient was advised to get an EMG and follow up with neurology, the dose of prednisone was decreased to 40 mg daily and advised to take vitamin D 50,000 units weekly. Conclusion: Anti-NXP2 antibody positive JDM has a poor prognosis compared to other subcategories. This stems from increased risk of malignancies and calcinosis leading to fatalities. Our patient was a rare case with anti-NXP2 antibody positive JDM, Myasthenia gravis, and Hurthle cell cancer. There is an increased need in data and research regarding NXP2 antibody and its heterogenous prognosis with DM patients.