Autoimmune Symptoms Research Articles

Prediction and expression analysis of deleterious nonsynonymous SNPs of Arabidopsis ACD11 gene by combining computational algorithms and molecular docking approach.

Accelerated cell death 11 (ACD11) is an autoimmune gene that suppresses pathogen infection in plants by preventing plant cells from becoming infected by any pathogen. This gene is widely known for growth inhibition, premature leaf chlorosis, and defense-related programmed cell death (PCD) in seedlings before flowering in Arabidopsis plant. Specific amino acid changes in the ACD11 protein’s highly conserved domains are linked to autoimmune symptoms including constitutive defensive responses and necrosis without pathogen awareness. The molecular aspect of the aberrant activity of the ACD11 protein is difficult to ascertain. The purpose of our study was to find the most deleterious mutation position in the ACD11 protein and correlate them with their abnormal expression pattern. Using several computational methods, we discovered PCD vulnerable single nucleotide polymorphisms (SNPs) in ACD11. We analysed the RNA-Seq data, identified the detrimental nonsynonymous SNPs (nsSNP), built genetically mutated protein structures and used molecular docking to assess the impact of mutation. Our results demonstrated that the A15T and A39D mutations in the GLTP domain were likely to be extremely detrimental mutations that inhibit the expression of the ACD11 protein domain by destabilizing its composition, as well as disrupt its catalytic effectiveness. When compared to the A15T mutant, the A39D mutant was more likely to destabilize the protein structure. In conclusion, these mutants can aid in the better understanding of the vast pool of PCD susceptibilities connected to ACD11 gene GLTP domain activation.

Autoimmune Skin Disease Exacerbations Following COVID-19 Vaccination.

BackgroundVaccination against COVID-19 reduces the risk of severe COVID-19 disease and death. However, few studies have examined the safety of the COVID-19 vaccine in patients with autoimmune skin disease.ObjectivesWe sought to determine the incidence of disease exacerbation in this population following COVID-19 vaccination as well as the associated factors.MethodsWe performed a chart review of all patients seen in the autoimmune skin disease clinic of the principal investigator during the study period. All patients included for analysis were systematically and prospectively asked about COVID-19 vaccination status, manufacturers, vaccine dates, autoimmune symptoms after the vaccine, and timing of symptom onset using a standardized template as part of their visit. Demographics and autoimmune disease diagnosis were also collected. Analysis used Chi-square and Fisher’s exact tests.Results402 subjects were included for analysis. 85.6% of patients were fully vaccinated, with 12.9% unvaccinated and 1.5% partially vaccinated. 14.8% of fully vaccinated patients reported worsening autoimmune signs and symptoms after the vaccine. Fully vaccinated dermatomyositis patients were more likely to report worsening autoimmune signs and symptoms after the vaccine (22.7%) than fully vaccinated lupus erythematosus patients (8.6%) (p=0.009). Patients fully vaccinated with the Moderna vaccine trended towards an increased likelihood of reporting worsening autoimmune signs and symptoms after the vaccine (19.1%) than those with the Pfizer-BioNTech vaccine (12.0%) (p=0.076). Of the patients who had autoimmune symptoms after vaccination, 20% had symptoms after the 1st dose, 82% after the 2nd dose, and 4% after the 3rd dose with median onset (95% confidence interval) of 7 (2,14), 14 (14,21), and 18 (7,28) days later, respectively.ConclusionsMore fully vaccinated dermatomyositis patients had exacerbation of autoimmune signs and symptoms after the vaccine than fully vaccinated lupus erythematosus patients. However, given the risks of COVID-19, clinicians should still promote vaccination in most patients with autoimmune skin disease.

Breast Implant-Associated Immunological Disorders.

Background Breast implants are commonly placed postbreast cancer reconstruction, cosmetic augmentation, and gender-affirming surgery. Breast implant illness (BII) is a systemic complication associated with breast implants. Patients with BII may experience autoimmune symptoms including fatigue, difficulty concentrating, hair loss, weight change, and depression. BII is poorly understood, and the etiology is unknown. The purpose of this literature review is to characterize BII autoimmune disorders and determine possible causes for its etiology. Methods The PubMed, Google Scholar, Embase, Web of Science, and OVID databases were interrogated from 2010 to 2020 using a query strategy including search term combinations of “implants,” “breast implant illness,” “autoimmune,” and “systemic illness.” Results BII includes a spectrum of autoimmune symptoms such as fatigue, myalgias/arthralgias, dry eyes/mouth, and rash. A review of epidemiological studies in the past ten years exhibited evidence affirming an association between breast implants and autoimmune diseases. The most commonly recognized were Sjogren's syndrome, rheumatoid arthritis, systemic sclerosis, chronic fatigue syndrome, and Raynaud's syndrome. Explantation resulted in alleviation of symptoms in over 50% of patients, strengthening the hypothesis linking breast implants to BII. Studies have shown that silicone is a biologically inert material and unlikely to be the cause of these symptoms. This is supported by the fact that increased risk of autoimmune disease was also reported in patients with other implantable biomaterials such as orthopedic implants. Recent studies shed light on a possible role of bacterial biofilm and subsequent host-pathogen interactions as a confounding factor to this problem. Conclusion BII could be dependent on biofilm infection and the microenvironment around the implants. The true pathophysiology behind these complaints must be further investigated so that alternative treatment regimens other than explantation can be developed. Translational significance of these studies is not limited to breast implants but extends to other implants as well.

Alpha-synuclein peptides presented on chimeric MHC class Ib molecules prevent loss of substantia nigra neurons in an animal model for Parkinson’s disease

Abstract Aim An accumulating body of evidence suggests the involvement of alpha-synuclein (aSyn) specific autoreactive T cells in Parkinson’s disease (PD). Here, we investigate whether novel antigen-specific tolerance-inducing biomolecules, that present peptide antigens on MHC class Ib-related molecules, can inhibit neurodegeneration and prevent PD in vivo. Methods The alpha3 domain of the human MHC class Ib molecule HLA-G inhibits T cells via the human ILT-2 or the murine PIRB receptor. We fused this HLA-G alpha3 domain to MHC class I alpha1-alpha2 antigen presenting domains, antigenic peptides and beta2-microglobulin. These single-chain AutoImmunity Modifying Biologicals (AIM Bios) induce antigen-specific tolerogenic CD8+ Treg cells in human cells in vitro and in mice in vivo. We used this platform to prevent autoimmune disease symptoms in mouse models for autoimmune diseases, including an aSynA53T-AAV driven model for PD. Results Single-chain model AIM Bios with MHC-derived antigen-presenting domains and antigenic peptides polarize cognate CD8+ T cells towards a CD8+CD122+ IL-10 secreting Treg phenotype. Such antigen-specific Treg can also be induced in mice in vivo. Disease-associated aSyn CD8+ epitopes were identified in aSynA53T-AAV PD mice. Corresponding AIM Bios prevented mobility impairments. Post mortem histopathological assessment confirmed the induction a favorable in-situ immune cell composition and the rescue of substantia nigra neurons. The translational potential of this approach deserves further exploration. Supported by grants from the IZKF Wuerzburg A421 and by Aeterna Zentaris Inc.

Effect of COVID-19 on Severity of Signs and Symptoms of Autoimmune Diseases

It is an observational cross-sectional study, the data collected by convenience sampling method from 33 patients in the Ranya General Hospital and private clinics for follow-up patient’s autoimmune diseases state in the Ranya city from the 10th November 2020 to the 20th May 2021 and the study included all the patients had autoimmune diseases that recovered from the COVID-19 disease. For the study materials, the data was collected by a questionnaire form that included demographic and autoimmune disease questions also questions about the patient’s intensity of their autoimmune disease’s signs and symptoms before and after they recovered from COVID-19. Determine patient’s autoimmune disease signs and symptoms intensity based on the prescribed drug for a treat the autoimmune diseases which are changed by special doctors. Furthermore, the data were analysed by SPSS software to produce descriptive statistic measures and to find the difference between dependent categorical variables Sign tests were used but the Chi-square test was used for the categorical independent variables with regarding 0.05 as a significant critical value. The result reveals that the range of their age started from 42 to 74 years old with mean±standard deviation (57.3 ± 8.06) and most of the cases 15(45.5%) were between (55-65) years old, followed by less than 55 years old 13(39.4%) and more than 65 years old age 5(3.8%) cases respectively. Rheumatoid arthritis was a major type 16 (48.5%) of the autoimmune disease compared to other types, Ankylosing Spondylitis 8(24.2%) cases, and Ulcerative Colitis 6(18.2%) cases respectively while Crohn's disease was the minimum 3(9.1%) cases and before the got COVID-19 most of the cases 25(75.8%) had moderate intensity signs and symptoms of their autoimmune diseases and 8(24.2%) cases had severe signs and symptoms but after they recovered from the COVID-19 disease the rate of their signs and symptoms changed to mild 19(57.6%) and moderate 14(42.4%) intensity while severe intensity signs and symptoms were zero with highly significant differences (P-value 0.0001). Despite the current study concluded autoimmune disease patients recovered from the COVID-19 their autoimmune diseases signs and symptoms intensity decreased significantly but still further studies are needed with a bigger sample size to determine and explain this association.

Dual autoimmune diseases: Rheumatoid arthritis with systemic lupus erythematosus and Type 1 diabetes mellitus with multiple sclerosis

AbstractAutoantibodies and inflammation are the hallmarks of autoimmune diseases (ADs). Organ‐specific and nonorgan‐specific ADs are divided according to whether the autoimmune reaction is directed against a specific tissue (e.g., thyroid in Hashimoto's thyroiditis) or widely expressed antigens (e.g., cell nuclei in systemic lupus erythematosus [SLE]). SLE is distinguished by the presence of circulating autoantibodies and immune complex deposition, both of which can induce inflammatory damage to many organs. Rheumatoid arthritis (RA), sometimes called inflammatory arthritis, is a systemic AD that affects the joints and causes synovitis. Multiple sclerosis (MS) is a central nervous system inflammatory disease with various neurological and autoimmune symptoms. Links have been reported between RA and SLE as well as between Type 1 diabetes mellitus and MS. Identification of shared genes and biological processes could aid in the discovery of possible treatment targets in these dual ADs. This review article explores the molecular nature and familial inheritance of dual ADs.

PD-1 cooperates with AIRE-mediated tolerance to prevent lethal autoimmune disease

Immunological tolerance is established and maintained by a diverse array of safeguards that work together to protect against autoimmunity. Despite the identification of numerous tolerogenic processes, the basis for cooperation among them remains poorly understood. We sought to identify synergy among several well-defined tolerance mediators that alone provide protection only from mild autoimmune symptoms in C57BL/6 mice: BIM, AIRE, CBL-B, and PD-1. Survey of a range of compound mutant mice revealed that the combined loss of the autoimmune regulator, AIRE, with PD-1 unleashed a spontaneous, lethal autoimmune disease. Pdcd1−/−Aire−/− mice succumbed to cachexia before adulthood, with near-complete destruction of the exocrine pancreas. Such fatal autoimmunity was not observed in Pdcd1−/−Bim−/−, Bim−/−Aire−/−, or Cblb−/−Bim−/− mice, suggesting that the cooperation between AIRE-mediated and PD-1–mediated tolerance was particularly potent. Immune profiling revealed largely normal development of FOXP3+ regulatory T (Treg) cells in Pdcd1−/−Aire−/− mice, yet excessive, early activation of effector T cells. Adoptive transfer experiments demonstrated that autoimmune exocrine pancreatitis was driven by conventional CD4+ T cells and could not be prevented by the cotransfer of Treg cells from wild-type mice. The development of autoimmunity in mixed bone marrow chimeras supported these observations, indicating that failure of recessive tolerance was responsible for disease. These findings reveal a potent tolerogenic axis between AIRE and PD-1 that has implications for our understanding of how immune checkpoint blockade might synergize with subclinical defects in central tolerance to elicit autoimmune disease.

PD-1 agonism by anti-CD80 inhibits T cell activation and alleviates autoimmunity.

Targeted blockade of the checkpoint molecule programmed cell death 1 (PD-1) can activate tumor-specific T cells to destroy tumors, whereas targeted potentiation of PD-1 is expected to suppress autoreactive T cells and alleviate autoimmune diseases. However, the development of methods to potentiate PD-1 remains challenging. Here we succeeded in eliciting PD-1 function by targeting the cis-PD-L1-CD80 duplex, formed by binding of CD80 to the PD-1 ligand PD-L1, that attenuates PD-L1-PD-1 binding and abrogates PD-1 function. By generating anti-CD80 antibodies that detach CD80 from the cis-PD-L1-CD80 duplex and enable PD-L1 to engage PD-1 in the presence of CD80, we demonstrate that the targeted dissociation of cis-PD-L1-CD80 duplex elicits PD-1 function in the condition where PD-1 function is otherwise restricted. We demonstrate using murine models that the removal of PD-1 restriction is effective in alleviating autoimmune disease symptoms. Our findings establish a method to potentiate PD-1 function and propose the removal of restraining mechanisms as an efficient strategy to potentiate the function of inhibitory molecules.

Intracellular virus sensor MDA5 mutation develops autoimmune myocarditis and nephritis

Mutations in IFIH1 gene encoding viral RNA sensor MDA5 have been reported responsible for many interferonopathies, including Aicardi-Goutières syndrome (AGS) and monogenic lupus, however, the pathological link between IFIH1 mutations and various autoimmune symptoms remains unclear. Here, we generated transgenic mice expressing human MDA5 R779H mutant (R779H Tg), reported in AGS and monogenic lupus patient. Mice spontaneously developed myocarditis and nephritis with upregulation of type I IFNs in the major organs. R779H Tg Mavs−/− and R779H Tg Ifnar−/− showed no phenotypes, indicating direct MDA5-signaling pathway involvement. Rag-2 deficiency and bone marrow cells transfer from wild type to adult mice did not prevent myocarditis development, while mice with cardiomyocyte-specific expression of hMDA5 R779H showed cardiomegaly and high expression of inflammatory cytokines. Taken together, our study clarifies that type I IFNs production and chemokines from cardiomyocytes starts in neonatal period and is critical for the development of myocarditis. Activated lymphocytes and auto-antibodies exacerbate the pathogenesis but are dispensable for the onset.

Correlation between circulating MicroRNA-142-5p expression and Hashimoto's thyroiditis diagnosis and autoimmunity symptoms prediction, pilot study

PurposeTo assess the role of microRNA-142-5p (miR-142-5p) expression alongside serum anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TG) proteins in the autoimmune process of Hashimoto's thyroiditis (HT). MethodsEighty patients with HT and 80 subjects with age and sex compatibility as controls constitute the study participants in this case-control study. The miR-142-5p gene expression is measured in all the study populations by real-time PCR. We assessed the correlation between the miR-142-5p expression with serum anti-TPO and anti-TGA proteins (by enzyme-linked immunosorbent assay (ELISA)), clinical manifestations, and laboratory findings. ResultsThere was a significant difference (p < 0.001) between the patients with HT and controls regarding the miR-142-5p expression levels (Mean ± SD, 110.85 ± 333.14 and 0.09 ± 0.05 respectively). It showed a high diagnostic value at the cutoff point, 0.24 with sensitivity, 97%, specificity, 100%, positive predictive value (PPV), 98%, negative predictive value (NPV), 100%, and accuracy, 99%. Univariate binary logistic regression analysis showed that miR-142 (p = 0.004), anti-TPO (p < 0.001) and anti-TG (p < 0.001) were statistically significant predictors of HT. MiR-142-5p expression was significant, with some of the symptoms suggesting hypothyroidism, autoimmunity, and hypertension. ConclusionsmiR-142-5p expression may be a helpful tool in the diagnosis of HT and autoimmunity symptoms prediction.

Therapeutic Development by Targeting the cGAS-STING Pathway in Autoimmune Disease and Cancer.

DNA immune recognition regulation mediated by the cGAS-STING pathway plays an important role in immune functions. Under normal physiological conditions, cGAS can recognize and bind to invading pathogen DNA and activate the innate immune response. On the other hand, abnormal activation of cGAS or STING is closely related to autoimmune diseases. In addition, activation of STING proteins as a bridge connecting innate immunity and adaptive immunity can effectively restrain tumor growth. Therefore, targeting the cGAS-STING pathway can alleviate autoimmune symptoms and be a potential drug target for treating cancer. This article summarizes the current progress on cGAS-STING pathway modulators and lays the foundation for further investigating therapeutic development in autoimmune diseases and tumors.

Neurological autoimmune diseases following vaccinations against SARS-CoV-2: a case series.

Background and purposePopulation‐based studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines may trigger immune‐mediated thrombotic thrombocytopenia (VITT) raising concerns for other autoimmune responses. The aim was to characterize neurological autoimmunity after SARS‐CoV‐2 vaccinations.MethodsIn this single‐centre prospective case study patients with neurological autoimmunity in temporal association (≤6 weeks) with SARS‐CoV‐2 vaccinations and without other triggers are reported. Clinical, laboratory and imaging data were collected with a median follow‐up of 49 days.ResultsIn the study period 232,603 inhabitants from the main catchment area of our hospital (Rhein‐Neckar‐Kreis, county) received SARS‐CoV‐2 vaccinations. Twenty‐one cases (new onset n = 17, flares n = 4) diagnosed a median of 11 days (range 3–23) following SARS‐CoV‐2 vaccinations (BNT162b2 n = 12, ChAdOx1 n = 8, mRNA‐1273 n = 1) were identified. Cases included VITT with cerebral venous sinus thrombosis (n = 3), central nervous system demyelinating diseases (n = 8), inflammatory peripheral neuropathies (n = 4), myositis (n = 3), myasthenia (n = 1), limbic encephalitis (n = 1) and giant cell arteritis (n = 1). Patients were predominantly female (ratio 3.2:1) and the median age at diagnosis was 50 years (range 22–86). Therapy included administration of steroids (n = 15), intravenous immunoglobulins in patients with Guillain–Barré syndrome or VITT (n = 4), plasma exchange in cases unresponsive to steroids (n = 3) and anticoagulation in VITT. Outcomes were favourable with partial and complete remissions achieved in 71% and 24%, respectively. Two patients received their second vaccination without further aggravation of autoimmune symptoms under low‐dose immunosuppressants.ConclusionsIn this study various neurological autoimmune disorders encountered following SARS‐CoV‐2 vaccinations are characterized. Given the assumed low incidence and mostly favourable outcome of autoimmune responses, the benefits of vaccinations outweigh the comparatively small risks.

Optineurin modulates the maturation of dendritic cells to regulate autoimmunity through JAK2-STAT3 signaling

Optineurin (OPTN) has important functions in diverse biological processes and diseases, but its effect on dendritic cell (DC) differentiation and functionality remains elusive. Here we show that OPTN is upregulated in human and mouse DC maturation, and that deletion of Optn in mice via CD11c-Cre attenuates DC maturation and impairs the priming of CD4+ T cells, thus ameliorating autoimmune symptoms such as experimental autoimmune encephalomyelitis (EAE). Mechanistically, OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. Without such a negative regulation, Optn-deficient DCs eventually induce an IL-10/JAK2/STAT3/IL-10 positive feedback loop to suppress DC maturation. Finally, the natural product, Saikosaponin D, is identified as an OPTN inhibitor, effectively inhibiting the immune-stimulatory function of DCs and the disease progression of EAE in mice. Our findings thus highlight a pivotal function of OPTN for the regulation of DC functions and autoimmune disorders.

Prevalence and clinical correlates of antinuclear antibody in patients with gastroparesis.

Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders. 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA. Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), T1DM (16% of 162), T2DM (18% of 147), and postfundoplication (19% of 48 patients) gastroparesis. Among 536 patients with idiopathic gastroparesis, ANA titer 1:40-1:80 was seen in 33 (6%) patients, 1:160-1:320 in 36 (7%) patients, and ≥1:640 in 17 (3%) patients. Increasing ANA titer was associated with female gender (p=0.05), Hispanic ethnicity (p=0.02), comorbid rheumatoid arthritis (p=0.02), systemic sclerosis (p=0.004), and elevated ESR (p=0.007). ANA positivity was associated with lower total GCSI (p=0.007) and lower nausea/vomiting subscale (p=0.0005), but not related to gastric emptying. The prevalence of a positive ANA in patients with gastroparesis was high at ~17% and did not differ significantly based on etiology. In idiopathic patients, ANA positivity was associated with rheumatoid arthritis, systemic sclerosis, and elevated ESR. ANA-positive gastroparesis represents a subset who often have other autoimmune symptoms or disorders, but less severe nausea and vomiting.

Dose-dependent immunomodulatory effects of bortezomib in experimental autoimmune neuritis.

Proteasome inhibition with bortezomib has been reported to exert an immunomodulatory action in chronic autoimmune neuropathies. However, bortezomib used for the treatment of multiple myeloma induces a painful toxic polyneuropathy at a higher concentration. Therefore, we addressed this controversial effect and evaluated the neurotoxic and immunomodulatory mode of action of bortezomib in experimental autoimmune neuritis. Bortezomib-induced neuropathy was investigated in Lewis rats using the von Frey hair test, electrophysiological, qPCR and histological analyses of the sciatic nerve as well as dorsal root ganglia outgrowth studies. The immunomodulatory potential of bortezomib was characterized in Lewis rats after experimental autoimmune neuritis induction with P253-78 peptide. Clinical, electrophysiological, histological evaluation, von Frey hair test, flow cytometric and mRNA analyses were used to unravel the underlying mechanisms. We defined the toxic concentration of 0.2 mg/kg bortezomib applied intraperitoneally at Days 0, 4, 8 and 12. This dosage induces a painful toxic neuropathy but preserves axonal regeneration in vitro. Bortezomib at a concentration of 0.05 mg/kg significantly ameliorated experimental autoimmune neuritis symptoms, improved experimental autoimmune neuritis-induced hyperalgesia and nerve conduction studies, and reduced immune cell infiltration. Furthermore, proteasome inhibition induced a transcriptional downregulation of Nfkb in the sciatic nerve, while its inhibitor Ikba (also known as Nfkbia) was upregulated. Histological analyses of bone marrow tissue revealed a compensatory increase of CD138+ plasma cells. Our data suggest that low dose bortezomib (0.05 mg/kg intraperitoneally) has an immunomodulatory effect in the context of experimental autoimmune neuritis through proteasome inhibition and downregulation of nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFKB). Higher bortezomib concentrations (0.2 mg/kg intraperitoneally) induce sensory neuropathy; however, the regeneration potential remains unaffected. Our data empathizes that bortezomib may serve as an attractive treatment option for inflammatory neuropathies in lower concentrations.

S1545 Acute Acalculous Cholecystitis Leading to the Diagnosis of Systemic Lupus Erythematosus

Introduction: Acute acalculous cholecystitis (AAC) involves inflammation of the gallbladder without the presence of gallstones, and is commonly seen in ill hospitalized patients. We present a case of acalculous cholecystitis as the initial presentation of systemic lupus erythematosus (SLE). Case Description/Methods: A 34-year-old woman presented with two weeks of fever, epigastric pain with nausea, and a 10-pound weight loss. Review of systems was positive for dry eyes, dry mouth, and myalgias. Past medical history was notable for miscarriage. Complete blood count was notable for thrombocytopenia, normocytic anemia, and neutropenia (with absolute neutrophil count of 660 10*3/uL). Comprehensive metabolic panel was notable for an elevated protein gap and slightly abnormal AST 161 IU/L and ALT 61 IU/L. CT abdomen demonstrated gallbladder wall thickening, with no evidence of cholelithiasis. RUQ ultrasound confirmed the absence of gallstones. HIDA scan showed non-visualization of the gallbladder consistent with cystic duct obstruction. Erythrocyte sedimentation rate was elevated at 56 mm/hr and ferritin was greater than 4000 ng/ml. Further testing revealed positive testing for ANA, double-stranded DNA, anti-ro, and lupus anticoagulant. Given the predominant autoimmune symptoms, she was started on prednisone 60 mg for newly diagnosed lupus with improvement of her symptoms. After discharge she was started on plaquenil and azathioprine, and steroids were tapered. Repeat testing confirmed persistent antibodies for antiphospholipid syndrome. She was lost to follow up 6 months after discharge. Discussion: GI manifestations of lupus can be vast, and include oral ulcers, mesenteric vasculitis, intestinal pseudo-obstruction, protein losing enteropathy, lupus associated pancreatitis, and serositis. Hepatobiliary manifestations include primary sclerosing cholangitis and autoimmune cholecystitis. The pathogenesis of AAC in SLE typically involves vasculitis, serositis, or thrombosis, and gallbladder histology often shows vasculitis of small vessel arteries and venules. Treatment typically involves percutaneous cholecystostomy tube placement or cholecystectomy; however, there have been case reports of successful treatment of AAC in SLE with high dose corticosteroids, often in combination with antibiotics or other immunosuppressants. Our case demonstrates the importance of considering underlying autoimmune conditions in patients presenting with gastrointestinal symptoms.

Informed DEcision for cerebrospinal fluid analysis after epiLeptic seizures- the IDEAL-score: A development and validation study

BackgroundThis observational study was done to develop a score based on clinical predictors that enables a guided decision for the necessity of cerebrospinal fluid (CSF) analysis after first unprovoked epileptic seizures and to validate this score in a retrospective patient cohort. MethodsClinical predictors were identified by two panels of epilepsy experts and selected according to content validity ratios. Based on these predictors a score was created and applied to a cohort of patients with first epileptic seizures. ResultsThe “IDEAL score” consists of 9 items (fever, prolonged disturbance of consciousness, headache, imaging results, cognitive dysfunction, status epilepticus, malignancy, autoimmune encephalitis symptoms) that are collected at two different time points (< 3 h [A-score]; > 3 h [B-score] after hospital admittance). A CSF analysis is recommended, if at least one clinical finding is present, either one of the items evaluated during the acute phase (A-score) or later in the diagnostic process (B-score). In 41 patients (13%) CSF analysis provided essential clues to the cause of the seizure. The combined IDEAL score reached a sensitivity of 98%, a specificity of 53%, a positive predictive value of 24% and a negative predictive value of 99% in this patient cohort. ConclusionsA CSF analysis after first epileptic seizures provided decisive etiological findings in only 13% of all investigated patients. The IDEAL score offers clinicians a simple and easy-to-implement algorithm to assess the necessity of a CSF analysis, and to prevent unnecessary diagnostic procedures.

HIT in the head: a systematic review of cerebral venous sinus thrombosis in classical and autoimmune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) causes thrombosis and thrombocytopenia, usually due to prior heparin exposure, so-called classical HIT. However, in the autoimmune form, the signs and symptoms of HIT occur without prior heparin exposure. Development of cerebral venous sinus thrombosis (CVST) secondary to HIT is a rare occurrence, with relatively few reports in the literature. There is a need to better understand the clinical presentation and treatment paradigms in these rare cases. Therefore, we present the first systematic review of CVST occurring in classical and autoimmune HIT. Cases of HIT-induced CVST were identified through a systematic search of Pubmed from the date of inception to March 2021. Literature search revealed 21 cases of HIT and associated CVST with six cases (28.6%) of autoimmune HIT. Patients presented with signs and symptoms consistent with increased intracranial pressure, intracerebral hemorrhage (ICH), and/or focal neurologic deficits. Headache was the most common symptom with 12 patients (60.0%) presenting as such. 10 patients (47.6%) included in the study developed ICH. Non-heparin anticoagulants, especially direct thrombin inhibitors, were the first-line treatment for the majority of patients (55.6%). Intravenous immunoglobulin (IVIG) was used as treatment for select patients (16.7%) with autoimmune HIT. Few patients received surgical intervention for CVST (14.3%) or ICH (30.0%). Four patients had a full recovery, four patients had residual deficits, and seven patients ultimately expired. Symptoms of HIT-induced CVST are often related to CNS dysfunction. Non-heparin anticoagulants are important to treat CVST, even when patients have concomitant ICH, and may be supplemented with IVIG if treating autoimmune HIT. Rapid identification and treatment of HIT-induced CVST is imperative in order to prevent morbidity and mortality.

Lifestyle Medicine in Practice: Nutrition as a Primary Means of Treatment

ObjectivesOur objective was to describe characteristics of lifestyle medicine (LM) clinicians, use of nutrition in practice, and reported patient outcomes following LM interventions. MethodsThis analysis used data from a closed survey administered to N = 3182 members of the American College of Lifestyle Medicine in the summer of 2019. A total of n = 1,286 respondents began the survey, and the sample of interest for this analysis (n = 612) was restricted to those > 18 yrs, self-identifying as a healthcare practitioner, completing the survey within the US, and indicating that they had observed or supervised patients following LM interventions or lifestyle modifications. ResultsThe sample of interest was 66% female and mean age (SD) was 51 (12). A total of 63% were MDs or DOs. Specialties were as follows: 26% family medicine, 20% internal medicine, 28% other, and 24% not boarded by an ABMS board. Only 24% were certified in LM, but 89% were practicing LM for some or all of their practice. Pillars of LM reported as being regularly incorporated into practice included: nutrition (95%), physical activity (91%), stress reduction (76%), healthy sleep (76%), social support (62%), and avoidance of addictive substances (58%). Total counts of clinicians who reported patient improvements using LM were as follows: weight loss (479), blood glucose (464), blood lipids (437), blood pressure (488), angina (116), atherosclerosis (77), autoimmune symptoms (214), chronic pain (300), and quality of life (497). Total counts of clinicians who reported reduction or discontinuation of medications following LM use were as follows: blood glucose (365), insulin (292), statins (320), high blood pressure (384), and autoimmune (124). ConclusionsResults of this survey provide proof of concept that (1) nutrition is the top-used modality among LM clinicians for treatment, and (2) health improvements and medication reductions following lifestyle interventions are feasible and are not limited to a few, individual practitioners. Further research on nutrition-based LM approaches, including calculation of effect sizes, rigorous randomized trials to test effectiveness of recommended lifestyle modifications, and large-scale cohort studies tracking LM patient populations are needed. Funding SourcesAmerican College of Lifestyle Medicine.

Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms

Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly selective, tight-binding antibody from a 1011-member antibody library using combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass spectrometry analyses demonstrate antibody interaction with an N-terminal region of CXCR2 that is part of the IL-8 epitope. The antibody strongly inhibits IL-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and alleviates hCXCR2-dependent experimental autoimmune encephalomyelitis symptoms in mice. As inappropriate neutrophil migration accompanies many diseases including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic obstructive pulmonary disease, and cancer, this antibody has potential for development as a therapeutic agent, akin to anti-TNF antibodies. However, an important difference here is that the antibody targets the chemokine receptor and competes with natural ligand, rather than targeting the ligand itself.