ANA Titer Research Articles

Increased serum IL-31 levels in chronic spontaneous urticaria and psoriasis with pruritic symptoms

BackgroundChronic spontaneous urticaria (CSU) is a common pruritic skin condition, the pathogenesis of which remains unclear. Interleukin-31 (IL-31) is a major pruritogenic cytokine that plays a role in inducing pruritus in various skin diseases. Aim.To 1) compare serum IL-31 levels among CSU patients, psoriasis patients with pruritic symptoms, and healthy subjects, 2) examine the correlations between serum IL-31 levels and disease severity, and 3) compare IL-31 levels in patients with and without CSU-associated auto-antibodies. MethodsPatients with CSU, psoriasis with pruritic symptoms, and healthy volunteers were recruited in the study. Serum IL-31 levels were measured with commercial kits. Baseline characteristics, urticaria activity score, psoriasis area severity index, pruritic intensity score, and related laboratory results were collected. ResultsSixty-five CSU patients, 30 psoriasis patients who had pruritus, and 31 healthy subjects participated in our study. The CSU patients had significantly higher mean serum IL-31 levels than the psoriasis patients (252.4 ± 115.5 vs 121.4 ± 16.6 pg/mL, P < 0.001). Both CSU and psoriasis patients also had significantly higher mean serum IL-31 when compared with the healthy subjects. Serum IL-31 levels of CSU and psoriasis patients did not differ significantly according to disease or itching severity. Thyroid antibodies and antinuclear antibodies were positive in 22 (33.8%) and 28 (43.1%) CSU patients, respectively. The CSU patients with ANA titers ≥1:160 had significantly higher mean serum IL-31 levels than in those who were negative for ANA and those with titers of 1:80 (P < 0.003 and P < 0.008, respectively). ConclusionHigher serum IL-31 levels were found in patients with CSU and psoriasis with pruritic symptoms. This suggests that IL-31 has a possible role in the pathogenesis of CSU and psoriasis with pruritic symptoms.

A Novel Therapeutic DNA Vaccine Elicits Reduction of Tumor Clones and Favorable Perturbations in the Immune Microenvironment in Patients (pts) with Untreated Smoldering Waldenström Macroglobulinemia (sWM)

A Novel Therapeutic DNA Vaccine Elicits Reduction of Tumor Clones and Favorable Perturbations in the Immune Microenvironment in Patients (pts) with Untreated Smoldering Waldenström Macroglobulinemia (sWM)

Two Rare Cases of Severe Autoimmune Dyserythropoiesis without Any Underlying Haematological Malignancy or Autoimmune Disease

Background: Autoimmune dyserythropoiesis is a rare disorder with only 4 adult cases and 3 paediatric cases reported in the literature. These suggest an underlying cause of haematological malignancy i.e. CLL or autoimmune disorder e.g. SLE1. Two proposed mechanisms of the pathophysiology include erythroblastic synartesis, or a Fas deficiency in autoimmune conditions2. There is no standard of care, however most cases respond to immunosuppression and/or treatment of the underlying condition. This is a report of 2 rare cases of severe autoimmune dyserythropoiesis without any underlying haematological or autoimmune conditions that have both responded to immunosuppression. Methods: Investigations included a haemolytic screen (LDH, bilirubin, haptoglobin, reticulocyte count and DAT), iron, B12 and folate studies, viral screening (EBV, CMV, HBV, HCV, HIV and parvovirus serologies and parvovirus PCR), autoimmune screen (ENA, ANA, RF, anti CCP, dsDNA, ANCA, C3/4), malignancy screen (EPG/IEPG and serum light chains, peripheral blood flow cytometry and imaging including CT CAP and/or PET scans). Bone marrow aspirate and trephine were performed with cytogenetics and molecular testing for myeloid mutations using NGS panels. Results: Case 1 is a 56-year-old female who initially presented in 2006 with fevers, weight loss, night sweats and an unexplained anaemia with a haemoglobin of 67g/L and MCV of 109 fl. WCC was 6.3 x10^9/L and platelet count 495 x 10^9/L. Clinical exam revealed no signs of haematological malignancy or autoimmune disease. Reticulocyte count was low at 7x10^9/L. ESR was significantly elevated at 130 mm/hr. Bone marrow biopsy was hypercellular with increased early erythroid precursors and some erythroid islands that resembled erythroblastic synartesis. Moderate dyserythropoiesis with numerous binucleate forms was also noted. The rest of her investigations were normal. She responded briskly to low dose prednisone (25mg daily) with resolution of her anaemia, reticulocytopaenia and inflammatory markers. She was transitioned onto azathioprine in 2011 as a steroid sparing agent which was ceased in 2018 due to a diagnosis of localised breast cancer. She remained in remission off immunosuppression for 18 months. Her relapse clinical findings and investigations were identical to her initial presentation. Her NGS testing at this time was negative for myeloid genetic mutations. She again responded briskly to prednisolone. Case 2 is a 65-year-old female referred for a 4th opinion in May 2019 regarding transfusion dependent anaemia. Clinical exam revealed no signs of malignancy nor autoimmune disease. Haemoglobin averaged 60g/L with a low reticulocyte count at 11x10^9/L and elevated MCV of 117fL. Ferritin was elevated secondary to multiple prior transfusions at 1190 ug/L. ESR and CRP were elevated with an ANA titre of 1:80 (homogenous). Bone marrow was hypercellular with some minor dysplastic features and increased immature forms. Peripheral blood flow cytometry revealed a small monoclonal B cell population (0.1% of lymphocytes) that was not detected on bone marrow biopsy. The rest of her investigations were normal. She declined a trial of steroid therapy She was commenced on weekly IV rituximab 375mg/m2 for 3 weeks but was unable to tolerate mild infusion reactions and had no response. She was then treated with intravenous immunoglobulin as well as iron chelation therapy and her anaemia, reticulocytopaenia and inflammatory markers quickly resolved. Discussion: These are two rare cases of severe autoimmune dyserythropoiesis with reticulocytopaenia with no autoimmune haemolysis and no underlying autoimmune or malignant disease. Due to the rarity of this disease, there are no clear guidelines on how to manage these patients and more evidence/research is required. Both cases responded well to immunosuppressive treatment in a relapsing/remitting fashion that further reinforces the autoimmune nature of this disease.One patient did not respond to rituximab despite a small monoclonal B lymphocyte population unlike the only other case treated with rituximab reported where this was successful.

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD).

Background and ObjectivesUnderstanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure.MethodsWe prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively.ResultsThirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils.ConclusionsWe are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.

A RARE CASE OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic lupus erythematosus (SLE) interstitial lung disease (ILD) is a spectrum of disease that is further characterized by histopathology. Among the literature, usual interstitial pneumonia (UIP) appears to be the rarest form. We present a case of a young female with this rare phenomenon. CASE PRESENTATION: A 38 year old female with a history of SLE was evaluated by pulmonology outpatient for progressively worsening dyspnea on exertion. Rest relieved the dyspnea and she could walk approximately 30 feet before having to stop. CT pulmonary angiography was negative for pulmonary emboli but showed peripheral interstitial markings bilaterally, greatest in the lower lobes. Pulmonary function test showed mild to moderate restrictive lung disease. Bronchoscopy, transbronchial biopsy, and serologic workup was negative except for elevated ANA. Since her diagnosis of SLE, she only had known joint involvement. ANA titer was 1:320. A repeat CT chest several months later showed subpleural interstitial markings within both upper lobe zones and more pronounced at the bases. CT surgery evaluated her and performed a video assisted thoracoscopy with biopsy of lower lung. Biopsy revealed a honeycomb pattern suggestive of UIP and idiopathic pulmonary fibrosis (IPF). A second opinion by a pathologist at a large academic center confirmed the initial diagnosis. She required supplemental oxygen for hypoxia on exertion and started mycophenolate with eventual addition of pirfenidone. Her symptoms improved and she is being evaluated for lung transplantation. DISCUSSION: Although SLE-UIP is rare, clinicians should remain diligent about thoroughly reviewing past medical history and having a broad differential for patients presenting with dyspnea. SLE-UIP has multiple forms including acute, subacute, and chronic although most cases have non-specific findings on high resolution CT or histopathology to subclassify the disease [1]. The prognosis is better than IPF/UIP associated with other connective tissue diseases [1,2,3] with a 5 year mortality rate of approximately 85% [1]. Literature on SLE-UIP is predominantly case reports and the ideal treatment has not been identified but most patients receive glucocorticosteroids with addition of immunsuppressive therapy if needed. In our patient, perhaps she will receive a lung transplant. CONCLUSIONS: Usual interstitial pneumonia in the setting of systemic lupus erythematosus is uncommon with few reported cases. To optimize treatment, further studies are warranted. Reference #1: Enomoto N, Egashira R, Tabata K, et al. Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study. Sci Rep. 2019;9(1):7355. Reference #2: Nakamura Y, Chida K, Suda T, et al. Nonspecific interstitial pneumonia in collagen vascular diseases: comparison of the clinical characteristics and prognostic significance with usual interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20(3):235-41. Reference #3: Enomoto N, Suda T, Kato M, et al. Quantitative analysis of fibroblastic foci in usual interstitial pneumonia. Chest. 2006;130(1):22-9. DISCLOSURES: No relevant relationships by Bharat Avirneni, source=Web Response No relevant relationships by Christopher Rosse, source=Web Response No relevant relationships by Christopher Schmitt, source=Web Response

S3512 When Your Defense Goes Rogue

INTRODUCTION: Humans have innate and adaptive defense mechanisms that, collectively, protect us against diseases and infections. But a malfunction of our immune system may cause harm in the form of autoimmune diseases. CASE DESCRIPTION/METHODS: We present a 29 year old female with no PMH who sought outpatient evaluation for new onset jaundice. With the intent of losing weight, the patient followed a strict diet, consisting of apples and water with one ‘cheat’ meal per week. In conjunction, patient reported using a daily herbal extract with containing green tea and green coffee bean extract. There was no family history of liver or autoimmune disease. After 4 months, she developed nausea, vomiting and jaundice. She was hemodynamically stable and afebrile. With the exception of jaundice the physical examination was unremarkable. Imaging (CT and MRI) of the liver revealed periportal edema. Initial laboratory evaluation showed ALT 960, AST 1162, T BR 17.3 & INR 1.9. HBV, HCV, HSV, HIV, EBV and CMV, Wilson’s disease and alpha 1 antitrypsin deficiency were ruled out as the cause of the patient’s acute liver injury. ANA titer was 1:1280 with a speckled pattern. Antimitochondrial, smooth muscle and liver kidney microsomal antibodies were negative. Due to persistent decompensation, liver biopsy was done with extensive hepatic necrosis. She was ultimately diagnosed with autoimmune hepatitis and treated with corticosteroids and later azathioprine. DISCUSSION: Although acute liver injury induced by green tea consumption has been described, the association with autoimmune hepatitis has been rarely reported. Green tea leaves contain polyphenols, flavonols and catechinis. The polyphenols have antioxidant, anticarcinogenic, anti-inflammatory, thermogenic and antimicrobial properties. Green tea extract has been associated with acute hepatitis and fulminant hepatic failure. The mechanisms leading to cytotoxicity include mitochondrial membrane destruction and induction of reactive oxygen species. Patients with autoimmune hepatitis may have symptoms of jaundice with hypergammaglobulinemia and positive serum antibodies (ANA, smooth muscle and liver kidney microsomal). The liver develops inflammation, necrosis and fibrosis for which therapy with corticosteroids and azathioprine are used. These findings were noted in our patient after several months of green tea and green coffee bean consumption. Therefore we hypothesize that green tea may, in rare circumstances, be the trigger of autoimmune hepatitis.

S2404 Acute Fatty Liver of Pregnancy in the Early Second Trimester Masquerading as Autoimmune Hepatitis

INTRODUCTION: Acute fatty liver of pregnancy (AFLP) is a rare and potentially fatal condition characterized by microvesicular steatosis and liver failure. It typically presents in the third trimester or early postpartum period, but several cases have been described in the second trimester, with the earliest reported case at 18 weeks gestation. Diagnosis is based on the Swansea Criteria, though liver biopsy can be performed under certain circumstances. Treatment involves supportive care and prompt fetal delivery, with recovery expected over the ensuing days to weeks. We present the earliest known case of AFLP at 15 weeks gestation and detail how its clinical course masqueraded as autoimmune hepatitis (AH). CASE DESCRIPTION/METHODS: A 41-year-old G4P2103 with morbid obesity was transferred to our institution with jaundice, scleral icterus, and vomiting after laboratory testing revealed AST 51 IU/L, ALT 88 IU/L, ALP 191 IU/L, and TB 15 mg/dL. On admission she was alert and oriented with stable vital signs. Laboratory testing was notable for an ANA with >1:1280 titer. Additional autoantibodies, anti-cardiolipin, and ADAMTS13 were negative. Blood smear showed no hemolysis. On day 2 an abdominal ultrasound revealed intrauterine fetal demise, so dilation and evacuation were performed. There was no evidence of preeclampsia or hemolysis with elevated liver enzymes and low platelets, so she was treated with methylprednisolone out of concern for AH. She did not improve with steroids so liver biopsy was performed which revealed mixed micro- and macrovesicular steatosis consistent with AFLP and nonalcoholic fatty liver disease (NAFLD). She was transferred to a liver transplant center where she expired without further intervention. DISCUSSION: This case was challenging because AFLP has never been reported in the early second trimester and the presence of high ANA titers suggested an autoimmune etiology. The biopsy showed mixed micro- and macrovesicular steatosis with cytoplasmic ballooning, mild inflammation, and no fibrosis. AH was excluded due to the lack of interface hepatitis, rosettes, plasma cell inflammatory changes, or improvement with steroids. Although NAFLD is associated with autoantibodies it does not cause acute liver failure, which this patient experienced despite receiving the standard of care. Therefore, based on the patient's clinical course and biopsy we present the earliest case of AFLP complicated by concomitant NAFLD.Figure 1.: Low power, hematoxylin and eosin (H&E) stained section showing mild steatosis in a zonal pattern, primarily involving zone 3. The inflammation is mild with a lobular predominance, composed principally of lymphocytes and plasma cells with smaller populations of neutrophils and eosinophils.Figure 2.: High power, hematoxylin and eosin (H&E) stained section showing cytoplasmic ballooning of hepatocytes with the presence of Mallory's Hyaline (arrows).Figure 3.: High power, hematoxylin and eosin (H&E) stained section of microvesicular (arrowheads) and macrovesicular (asterisk) steatosis.

HEMOPTYSIS WITH POSITIVE ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODY WITHOUT RENAL INVOLVEMENT: UNUSUAL PRESENTATION; IS THIS TRULY AN ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE?

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Anti-GBM disease is a small vessel vasculitis affecting glomerular and pulmonary capillaries due to deposition of anti-GBM autoantibodies along basement membrane. It is characterized by a triad of pulmonary hemorrhage, crescentic glomerulonephritis and circulating anti-GBM autoantibodies (1). In rare cases, pulmonary disease predominates. We report a patient with hemoptysis who was found to have positive anti-GBM Ab but normal renal function. CASE PRESENTATION: A 74-year-old male with 30 pack year smoking history and emphysema came into ED with sudden onset hemoptysis. He reported dry cough and a low-grade fever for a month that did not respond to antibiotics. CT angiogram showed bronchial wall thickening in mainstem and perihilar bronchi and secretions in the left mainstem. No pulmonary embolism, aneurysm or AVM was noted. Laboratory findings included hemoglobin drop from 17 to 14 mg/dl; normal white cell count, platelets, PT/PTT, serum creatinine, urinalysis and negative procalcitonin, respiratory viral panel, ESR and CRP. Bronchoscopy showed recent blood in left mainstem bronchus and multiple segmental bronchi with active oozing from inferior lingular subsegmental bronchus which was cauterized. There were no airway lesions to biopsy or broncholith eroding into the airway wall. BAL cultures were negative. On further testing, ANCA (MPO and PR3 IgG) antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibodies were not detected. However, serum ANA titer was 1:320 with speckled pattern and anti-GBM IgG antibody was 55 AU/ml. He was started on prednisone taper. Multidisciplinary discussion was held as with lack of inflammatory markers and classic radiographic findings, it was not clear if he truly had anti-GBM disease. Repeat serum ANA and Anti-GBM antibody were positive with a decrease in anti-GBM antibody titer from 55 to 41 AU/ml. Kidney biopsy was not obtained due to lack of renal involvement. He was continued on prednisone taper with initiation of mycophenolate. At 6 months follow-up, his anti-GBM titer decreased to 27 AU/ml without recurrence of hemoptysis or renal involvement. DISCUSSION: Pulmonary predominant anti-GBM disease is rare and accounts for <10% of all cases [1]. Our patient presented only with hemoptysis with no typical radiographic findings (diffuse alveolar hemorrhage) or renal involvement. It is possible that smoking or a respiratory infection triggered mucosal injury causing hemoptysis and positive anti-GBM Ab was an incidental early finding [2,3]. However, no other possible explanation for hemoptysis was found on bronchoscopy and his high titer of anti-GBM Ab decreasing with immunosuppressants makes this a plausible diagnosis. CONCLUSIONS: Clinicians should consider anti-GBM disease when patients present with hemoptysis without obvious etiology. Early diagnosis and treatment could potentially delay or even prevent renal involvement and may improve outcome. Reference #1: Justin A. Edward, Jeffrey S. Lee, Peter K. Moore, Andrew K. Levy. A Man in His 50s With Hemoptysis, Dyspnea, and Bilateral Patchy Ground-Glass Opacities. CHEST 2019; 156(2):e41-e45 Reference #2: Chin Jung, George Karpouzas, William W. Stringer. Dyspnea, Hemoptysis, Perihilar infiltrates in a 35-year-old man. CHEST 2005; 127:1437-1441 Reference #3: Emily Ann Boardman, Sameira Sohail, Rajesh Yadavilli. Goodpasture’s disease with late presentation of renal abnormality and anti-GBM autoantibody. BMJ Case Rep 2017. doi:10.1136/bcr-2016-218705 DISCLOSURES: No relevant relationships by Maria Azhar, source=Web Response No relevant relationships by Sukrita Menon, source=Web Response No relevant relationships by harikrishnan nandakumar, source=Web Response No relevant relationships by Ji Hyun Rhee, source=Web Response

S2635 A Unique Case of Neutrophilic Dermatitis (Sweet Syndrome) Associated With Primary Sclerosing Cholangitis: Case Report and Literature Review

INTRODUCTION: We present a unique case of Sweet Syndrome associated with primary sclerosing cholangitis. CASE DESCRIPTION/METHODS: A 39-year-old woman presented to the emergency department with diffuse necrotic skin lesions and recent uveitis. Her inflammatory markers were elevated. Serologic studies showed a positive ANA titer of 1:320 and p-ANCA titer of 1:80. A full-thickness skin biopsy revealed dense neutrophilic inflammation without evidence of vasculitis. Tissue cultures were negative. She was started on oral corticosteroids with complete resolution. She was found to have an elevated alkaline phosphatase of 677 U/L. Magnetic resonance cholangiopancreatography (MRCP) revealed intrahepatic ductal dilation in an irregular beaded pattern consistent with primary sclerosing cholangitis. She did not have any gastrointestinal symptoms and had a normal previous colonoscopy. DISCUSSION: Sweet Syndrome is an inflammatory condition characterized by the abrupt eruption of cutaneous lesions. Characteristic findings on histology include prominent edema in the dermis, a dense neutrophilic infiltrate, and endothelial swelling without vasculitis. The most common extra-cutaneous manifestation is uveitis. The pathogenesis of Sweet syndrome is unclear but has been postulated to be associated with immune and cytokine dysregulation. Sweet syndrome has been associated with multiple disorders including infections, inflammatory bowel disease (IBD), autoimmune, pregnancy, malignancies, and certain prescription medications. To our knowledge, this is the first described case of Sweet Syndrome associated with primary sclerosing cholangitis in a patient without IBD.Figure 1.: Skin Lesion.Figure 2.: Histology.Figure 3.: MRCP.

Serum level of CXCL 12 in patients with systemic lupus erythematosus: Is it worthy for predilection of lupus nephritis?

Aim of the workTo assess serum level of CXCL12 in systemic lupus erythematosus (SLE) patients and to study its relation to clinical features, disease activity and damage. Patients and methodsForty SLE patients and 40 controls were included. SLE disease activity index (SLEDAI) and the damage index were assessed. Serum CXCL12 level was measured using ELISA and renal biopsy done. ResultsThe mean age of the patients was 34.5 ± 10.4 years, disease duration 5 ± 5.2 years and were 38 females and 2 males (F:M 19:1). Renal biopsy was performed in 16 patients; 6 had inactive and10 active lupus nephritis (LN); 24 without signs suggestive of LN. Serum level of CXCL12 was significantly higher in patients (30.8 ± 16.9 ng/ml) than controls (20.2 ± 15.3 ng/ml) (p = 0.004). CXCL12 in patients with active LN (53.2 ± 25.3 ng/ml) was significantly elevated than those without LN (27 ± 12.5 ng/ml)(p < 0.001); and tended to be higher than those with inactive LN (34.2 ± 8.3 ng/ml)(p = 0.31). Levels were comparable between those with inactive LN and those without LN (p = 0.34). A significant correlation was found between serum CXCL12 and each of platelet count (p = 0.02), ANA titer (p = 0.007) and serum creatinine (p = 0.014). No significant correlations was found between CXCL12 and either SLEDAI (p = 0.59) or the damage index (p = 0.48). Alopecia was inversely associated with CXCL12 (p = 0.02). ConclusionCXCL12 is a potential key-player for SLE development. Adding this test to ANA, serum creatinine, platelet count and renal biopsy findings may enhance their diagnostic capacity for lupus nephritis and can help in early management and prediction of its prognosis.

Paraclinical serum markers as aids in the diagnosis of autoimmune encephalitis

Expert opinion suggests the presence ANA and thyroid antibodies may be helpful to diagnosis autoimmune encephalitis (AE). This study investigates the sensitivity of these serum markers in a cohort of 26 patients with AE. TPO-Ab, TG-Ab and ANA (titer ≥1:320) were present in 45%, 35% and 32% of patients tested, respectively. The prevalence of TPO-Ab (11.3%), TG-Ab (10.4%) and ANA ≥1:320 (3.3%) has been previously reported in disease-free populations. Although these antibodies represent non-specific markers of autoimmunity, this study demonstrated that TPO-Ab, TG-Ab and ANA were significantly elevated in AE compared to disease-free populations (p < .001, p = .003, p < .001, respectively).

Obituary for Professor Michael J. Day

On 10th May 2020, Michael Day passed away at the age of 59 after a terminal illness with cancer. There have been many messages and tributes to him. He had many interests and activities as a veterinarian and was involved with the British Veterinary Small Animal Association (BSAVA), the World Small Animal Veterinary Association (WSAVA) as well as being the senior editor of the Journal of Comparative Pathology. There is an online book of condolence with many tributes at http://www.tolbc.com/MichaelDay. Michael trained as a veterinarian at Murdoch University, Perth, Western Australia. He had a profound interest in small animal immunology, infectious diseases and pathology which was focused in his residency and PhD studies performed at Murdoch. Having completed his PhD he held postdoctoral positions in Bristol and Oxford before joining the University of Bristol in 1990 as a lecturer in veterinary pathology in the Veterinary School. In 2017 he left Bristol Veterinary School as emeritus professor in veterinary pathology. Michael had been taught at Murdoch by Susan Shaw, who also joined the University of Bristol in 1990, and they forged a long-term collaborative friendship. For example, they co-authored a chapter entitled “Recent developments in atopic dermatitis of companion animals” (In: Williams HC, ed., Atopic dermatitis: the epidemiology, causes and prevention of atopic eczema. Cambridge: Cambridge University Press, 2000; 233–244). Michael was renowned for his ability to teach immunology to veterinary undergraduates and postgraduates by making the complex seem accessible. This ability was put to use helping residents of the European College of Veterinary Dermatology in their Immunology workshops in Split and ESVD members at a workshop in York. He lectured all over the world at international conferences about small animals and their immune-mediated and infectious diseases. He co-authored, with Ronald Schulz, a successful and popular textbook that has been widely used for teaching veterinary students (Veterinary immunology: principles and practice, 2nd edition. Boca Raton, FL: CRC Press, 2013). He also wrote two other books published by CRC Press, Clinical immunology of the dog and cat and (co-authored with Susan Shaw) Arthropod-borne infectious diseases of the dog and cat. Michael was extraordinarily hard-working and meticulously organised. For example, when compiling the book Veterinary Allergy (Chichester, UK: Wiley, 2014), the editors asked him to write the introductory chapter on “The immunological basis of allergic diseases”. His was, as expected, the first manuscript submitted, on time and complete with no revisions required. Michael worked on various techniques during his residency and PhD studies on the immune system of companion animals, and this is reflected in one of his earliest publications entitled “Immunodiagnosis of autoimmune skin disease in the dog, cat and horse” (Day MJ, Penhale WJ, Aust Vet J 1986; 63: 65–68). His research training in Murdoch led to the establishment of a diagnostic laboratory at the University of Bristol that enabled clinicians to investigate various diseases and conditions; it included testing for immunoglobulins, ANA titres and interpretation of immunohistochemical results for various tissues. This helped to bring him into contact with many clinicians within and outside Bristol Veterinary School and with whom he collaborated, this work helped to contribute to Michael’s large list of over 340 publications. While at Bristol Veterinary School, Michael helped to develop the application of reagents in detecting canine immunoglobulin G subclasses, and this led to a series of studies of immune responses in various skin diseases in dogs including pyoderma, hypersensitivity disorders and immune-mediated diseases. He also published detailed substantial retrospective histopathological studies looking at demodicosis, auto-immune skin diseases, pyoderma and cutaneous lymphoma. Michael will be remembered by many for his engaging and collaborative approach to all things concerning the study of infectious and immune-mediated diseases in companion animals, as well as a substantial portfolio of work on experimental autoimmunity. He supervised numerous PhD students and postdoctoral fellows, and was an external examiner for many. In later years Michael explored his family history and, interestingly, it became apparent that his family had hailed from the southwestern England, from villages in the county of Somerset, before they moved out to Australia in the 19th Century. Consequently, when he worked for the University of Bristol and made his home in Cheddar in the Mendip Hills area of Somerset, he was not far from where his ancestors had set out for Australia. Our thoughts and sympathies are extended to his wife Mary and to his family.

P0080INTERLEUKIN-17A GENE POLYMORPHISM (RS2275913G&amp;gt;A) IN SLE PATIENTS

Abstract Background and Aims There are six IL-17-family ligands [IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (IL-25) and IL-17F]. Interleukin-17A (IL-17A) also commonly called IL-17, is produced by the T helper17 (Th17) subset of CD4+ T cells.Interleukin-17 and other Th17 cytokines are linked to the pathogenesis of diverse autoimmune and inflammatory diseases. IL-17A is detected in synovial fluids and synovium from RA patients and induces proinflammatory cytokine production from synoviocytes, also expression of IL-17A was higher in SLE patients and its level positively correlated with the severity of lupus nephritis, because of its contribution to increasing anti-double-stranded DNA (dsDNA) antibody production in SLE. The aim of the present study is to determine the IL-17A gene polymorphism (rs2275913 G&amp;gt;A) frequency in patients with SLE and lupus nephritis, and to determine the association of this polymorphism with the disease activity. Method This cross-sectional, observational, case control study was carried out on 50 females patients, with their age ranged from 15 to 50 years (mean 25.67±9.29 years) with SLE attending Mansoura University Hospital .A control group of 50 healthy females of matched age were also included. The patient group was subdivided into patients with and those without lupus Nephritis (35 and 15 patients, respectively). Lupus nephritis was confirmed by renal biopsy. All patients were subjected to a thorough clinical evaluation and routine laboratory tests. SLEDAI score was calculated for all patients to determine the degree of lupus activity. DNA extraction was performed for all patients as well as controls, One SNPs of IL-17A (rs2275913G&amp;gt;A) was genotyped utilizing PCR- RFLP technique. Results The frequency of rs2275913 A allele was significantly higher in SLE patients than the control group (34.0% vs. 21.0%, respectively; p=0.04, OR =1.9, 95%CI =1.03-3.65). While G allele was significantly higher in control group, (P=0.04)). Moreover, AA genotype was significantly higher in the SLE patients than in the control group (8.0% vs. 0.0%, respectively; p=0.036) and associated with higher SLEDAI, ANA, and anti-dsDNA antibodies titer, (P=0.03, P=.039, P=0.047 respectively).on the other hand there was no significant difference in GG and GA genotypes in the SLE patients versus the control group. The frequency of both genotype GA and AA was higher in the SLE patients than the controls (60% vs. 42%, respectivley; OR=2.07, CI-95%=0.9-5.59); although the difference was not statistically significant (P= 0.07).Although A allele was numerically higher in lupus nephritis group versus non nephritis group(37.0% vs 27.0%, respectively), the Analysis of the frequency of IL-17A rs2275913 alleles and genotypes showed no statistical differences between the two groups. Moreover there was no statistical significance between different genotypes in cases of nephritis regard lupus nephritis class (P=0.9) and no statistical significance between different genotypes (GG-GA-AA) regarding activity indices (AI) or chronicity indices (CI) in lupus nephritis group (P=0.18, P=0.56 respectively). Conclusion We suggest that there was a significant association between IL-17A rs2275913 G&amp;gt;A polymorphism and SLE, as A allele and AA genotype were increased in SLE patients, lupus nephritis especially those with high activity

Immune-phenotyping IRF5 genetic risk and in vivo targeting of Irf5 hyper-activation in mouse models of lupus

Abstract Genetic variations within interferon regulatory factor 5 (IRF5) associate with risk of systemic lupus erythematosus (SLE) and mice lacking Irf5 are protected from lupus onset and severity. Exactly how IRF5 functions in the context of SLE disease progression remains unclear. We sought to determine how IRF5 genetic risk contributes to SLE disease onset and severity, and whether targeting IRF5 with select inhibitors would alleviate disease severity and mortality. Studies were performed in blood from genotyped healthy donors, SLE patients and mouse models of murine lupus. In NZB/W F1 lupus mice, we found that Irf5 is already hyper-activated before clinical onset in a cell type-specific manner. In healthy donors carrying IRF5 genetic risk, we detected IRF5 hyper-activation in the myeloid compartment that drives a pre-symptomatic SLE immune-phenotype. In SLE patients, IRF5 hyper-activation correlates with SLEDAI and dsDNA titers. To test whether IRF5 hyper-activation is a targetable function, we developed novel inhibitors that are cell permeable, non-toxic and selectively bind to the inactive IRF5 monomer. Treatment of NZB/W F1 and MRL/lpr mice with inhibitor attenuated lupus pathology by reducing serum ANA and dsDNA titers. In NZB/W F1 mice, we detected significant reductions in the number of circulating plasma cells and age- or autoimmune-associated B cells (ABCs), which alleviated kidney pathology and improved overall survival. In ex vivo human studies, the inhibitor blocked SLE serum-induced IRF5 activation in healthy immune cells and reversed basal IRF5 hyper-activation in SLE immune cells. This study provides the first in vivo pre-clinical support for treating SLE patients with an IRF5 inhibitor.

Higher seroprevalence of hepatitis E virus in autoimmune hepatitis: Role of false-positive antibodies.

Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P=.006), had higher IgG levels (27g/dL vs 13g/dL; P=.03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P=.045), and were more likely to have another autoimmune disease (60% vs 16%; P=.03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17g/L vs 11g/L; P=.009), ANA (1:160 vs 1:60; P=.026) and ASMA titres (1:80 vs 1:40; P=.021). Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.

Clinical and immunological characteristics of 56 patients with systemic lupus erythematosusin Uganda.

ObjectivesThe prevalence and burden of SLE in Africa are poorly understood. This health-facility-based retrospective study aimed to describe the frequency and the clinical and immunological characteristics of SLE in Uganda.MethodsWe reviewed clinical notes of patients presenting with rheumatological complaints in two large rheumatology outpatient clinics in Uganda between January 2014 and December 2019.ResultsOf the 1019 charts reviewed, 5.5% (56) of the patients had confirmed SLE, with a median age of 29 (range: 14–65) years. The male-to-female ratio was ∼1:10, and 19.6% (11/56) of the patients had SLE and RA overlap syndrome. Patients presented with joint pains or swellings (n = 39, 69.6%), typical photosensitive malar rash (n = 34, 60.7%), oral ulceration (n = 23, 41.1%), anaemia (n = 14, 25.0%), hair loss and polyserositis (n = 12, 21.4% each), constitutional symptoms (n = 10, 17.9%), RP (n = 4, 7.1%) or LN (n = 3, 5.4%). ANA and anti-dsDNA autoantibodies were both positive in 25 (75.8%) of the 33 patients with available results. ANA titres were ≥1:160, with a median titre of 1:160 (range: 1:160 to 1:3200). Six patients had titres ≥1:320. The median dsDNA level was 80 (range: 40–283) IU. Ten patients had results of C3 and C4 complement protein levels and, of these, 4 patients had low C3 levels and 3 had low C4 levels.ConclusionSLE is uncommon among patients presenting with rheumatological complains in Uganda. SLE overlaps with RA in our setting, and a majority of patients present to care with complications.

Hydralazine Induced Lupus Nephritis

Renal involvement is uncommon in the hydralazine induced systemic lupus erythematosus. We conducted a retrospective study to identify patients with biopsy proven Hydralazine induced lupus nephritis. Material and Methods: In this retrospective study, patients who had a diagnosis of hydralazine-induced lupus and were on hydralazine prior to their diagnosis of biopsy proven lupus nephritis were included. Clinical and laboratory data were obtained from review of medical records. The median follow-up time was 12 months. Results: Medical records were reviewed between 2013 to 2017. Four patients had a diagnosis of biopsy proven hydralazine-induced lupus nephritis and were on hydralazine prior to their diagnosis. The median age was 68 years at the time of diagnosis. The majority of patients were Caucasian (75%). Three were female (75%) and three (75%) were exposed to hydralazine 100mg three times daily. All four patients had biopsy proven lupus nephritis (class II, III, IV, III/IV) with elevated serum creatinine and were positive for ANA (titer of 640-1280, homogenous pattern). Of the three patients tested, all were positive for anti-Histone antibody. Two patients had positive anti-dsDNA, and one of them had low C3 and C4. The level of Anti-dsDNA normalized at 3 months while low C3 in one patient persisted at 12months. All had negative C-ANCA and 3 of the 4 had positive P-ANCA. All had strong positive MPO titer and 2 of the 3 tested had positive PR3.In addition to withdrawal of hydralazine, all four patients were treated with steroids, hydroxychloroquine and mycophenolate mofetil. Two of four patients received PLEX and two received Cytoxan and hemodialysis. Conclusion: A timely diagnosis of hydralazine induced lupus nephritis can be critical. In addition to withdrawal of hydralazine, all patients also require aggressive treatment similar to idiopathic lupus nephritis.

Introducing the tolerogenic macrophage therapy as an alternative approach to manage systemic lupus erythematosus: a case series

Introduction: Systemic Lupus Erythematosus (SLE) has been quite an enigma in medicine. The possibility of the host own defense mechanism attacking itself is still quite difficult to understand. Patients who suffer from this disease tend to have a problem in their qualities of life, especially as the majority affect female in their productive ages. Conservative therapy to manage this disease is widely developed and implemented. Since the known therapies have several side effects and limitation, a need to develop a new strategy that can re-establish the “tolerance” mechanism of our immune system is increasingly needed. Immunotherapy is already a promising field in the strategy against autoimmune cases. In our facility, we developed immunotherapy called ToM (Tolerogenic Macrophage) which similar to Mreg (Regulatory Macrophage) in order to utilise the “tolerance” ability of this immune apparatus.Case: In this study, we present 2 cases of female patients who suffer from SLE, which underwent ToM Therapy in our Cellcure facility in RSPAD Gatot Soebroto Jakarta-Indonesia. After the procedure the patient was monitored one month and one year. Clinical and control parameter such as ANA (IF) and ANA profile was examined again in both patients to measure the effect of this therapy. The ANA titer and the titer of specific antibodies such as dsDNA, Nucleosomes and Histones results show significant reduction, accompanied by the improvement of the symptoms.Conclusion: ToM Therapy seems to have a good efficacy as immunotherapy for SLE. Further study needed to establish this approach.

Interferon score is increased in incomplete systemic lupus erythematosus and correlates with myxovirus-resistance protein A in blood and skin

ObjectivesPatients with incomplete systemic lupus erythematosus (iSLE) have lupus features, but do not meet classification criteria for SLE. Type I interferons (IFN) are important early mediators in SLE, and IFN upregulation in incomplete SLE may be associated with progression to SLE. Since many patients present with skin symptoms, the aim of this study is to investigate IFN type I expression and IFN-related mediators in the blood and skin of iSLE patients.MethodsTwenty-nine iSLE patients (ANA titer ≥ 1:80, symptoms < 5 years, ≥ 1 objectified clinical criterion), 39 SLE patients with quiescent disease (fulfilling ACR or SLICC criteria, SLEDAI ≤4), and 22 healthy controls were included. IFN signature was measured in whole blood, based on 12 IFN-related genes, using RT-PCR, and IFN-score was calculated. IFN-related mediators myxovirus-resistance protein A (MxA), IFN-γ-induced protein 10 (IP-10), and monocyte chemoattractant protein (MCP-1) were measured using ELISA. IFN type I expression in the unaffected skin was analyzed by immunostaining with MxA.ResultsIFN-score was increased in 50% of iSLE patients and 46% of SLE patients and correlated positively with the number of autoantibodies, anti-SSA titer, ESR, and IgG and negatively with C4 in iSLE. Levels of MxA correlated strongly with IFN-score (r = 0.78, p < 0.0001). Furthermore, MxA expression was found in 29% of unaffected skin biopsies of iSLE and 31% of SLE patients and also correlated with IFN-score (r = 0.54, p < 0.0001).ConclusionsIFN-score was increased in half of the iSLE patients, and given the correlation with complement and autoantibody diversity, this suggests a higher risk for disease progression. MxA in the blood and unaffected skin correlated strongly with the IFN-score and is possibly an easily applicable marker for IFN upregulation.

NIVOLUMAB-INDUCED MYOCARDITIS, MYOSITIS, AND RESPIRATORY FAILURE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Nivolumab is a checkpoint inhibitor first approved for the treatment of metastatic melanoma. Several autoimmune side effects have been reported secondary to nivolumab, including autoimmune pneumonitis, hepatitis, colitis, myocarditis and myositis. We describe a case of myocarditis and myositis with diaphragmatic muscle weakness leading to hypercarbic respiratory failure after treatment with nivolumab, a previously unreported constellation of adverse events CASE PRESENTATION: A 61 years old male with metastatic melanoma underwent resection melanoma and thereafter received his first dose of nivolumab. He presented 7 days later with atrial fibrillation and moderately reduced EF (41-49%) on Echocardiogram. His initial troponin was 2.95 NG/ML. He underwent a left heart catherization showing clean coronaries without any culprit lesions. His CPK was noted to be 4000 IU/L on admission with Aldolase of 84U/L. Patient was obtunded and a CT head showed multiple cerebral embolic strokes. He was intubated and mechanically ventilated. Patient failed multiple extubation trials and underwent tracheostomy insertion for respiratory support and PEG tube insertion for functional dysphagia. Patient underwent CT chest scan showing small lung volumes and elevated diaphragm without any evidence of pulmonary embolism. Patient was gradually weaned off mechanical ventilation to tracheal mask. His muscle strength also improved as his CPK trended down to 90 IU/L and his Aldolase also trended down to 17 U/L. His troponin trended down gradually to 0.08 NG/ML. His ANA titer was also noted to be elevated at 1:160. Patient refused EMG testing and refused to be started on corticosteroids. He was diagnosed with Nivolumab induced myocarditis, myositis, diaphragmatic weakness and was discharged to rehab after a 36 day hospital stay. DISCUSSION: Nivolumab has been recently reported to cause myositis, myocarditis and myasthenia like syndromes. Patients in those case series had elevated CPK, ANA titer and LDH. Onset of side effects is highly variable, ranging from 1 day post infusion to several months. Usually autoimmune side effects of nivolumab are treated with corticosteroids. Depending on the grade severity of the side effect, the decision to discontinue nivolumab is made. It is important to recognize autoimmune side effects of Nivolumab early as we could have spared the patient a tracheostomy placement had he been treated with corticosteroids early upon onset of side effects. CONCLUSIONS: Recognize diaphragmatic muscle weakness as a side effect of Nivolumab. Early treatment with corticosteroids can be life saving and helps shorten hospital stay. Discontinuing nivolumab use is appropriate, though it is unclear whether switching to other immune checkpoint inhibitor is a safer strategy. Further research is required as the use of immune checkpoint point increases in Oncology. Reference #1: Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al.Fulminant myocarditis withncombination immune checkpoint blockade. N Engl J Med 2016; 375:1749–1755. Reference #2: Nora Möhn et al. Acute progressive neuropathy–myositis–myasthenia-like syndrome associated with immune-checkpoint inhibitor therapy in patients with metastatic melanoma. Melanoma Research 6 March 2019. Reference #3: Syed S Mahmood et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. Journal of the American College of Cardiology Apr 2018, 71 (16) 1755-1764; https://doi.org/10.1016/j.jacc.2018.02.037 DISCLOSURES: No relevant relationships by Amit Chopra, source=Web Response No relevant relationships by Wafic Itani, source=Web Response No relevant relationships by Boris Medarov, source=Web Response No relevant relationships by Ali Wazir, source=Web Response