Negative Antinuclear Antibody Research Articles

The Onset of Antinuclear Antibodies (ANAs) as a Potential Risk Factor for Mortality and Morbidity in COVID-19 Patients: A Single-Center Retrospective Study.

The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) (p < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; p < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; p < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; p < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients.

#2989 Superposition of atypical hemolytic syndrome and tubulointerstitial nephritis, a case report

Abstract Background and Aims Hemolytic uremic syndrome is a heterogeneous group of diseases that have in common the development of thrombotic microangiopathy with diffuse endothelial damage, resulting in the classic triad composed of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury, on the other hand, tubulointerstitial nephritis is characterized by the presence of inflammatory infiltrates and edema and of the interstitial compartment that causes deterioration of renal function. Method The following is the case of a patient with acute kidney injury of etiology composed of thrombotic microangiopathy and tubulointerstitial nephritis. Results 27-year-old female patient without significant history, began 3 weeks prior to admission with fever, chills, asthenia, nausea and vomiting of food content, approximately 5 episodes per day for 3 days, presenting intermittent episodes of jaundice of the mucous membranes and conjunctivae, with progressive increase of the symptoms to the point of preventing daily activities, she was admitted for study, detecting hemolytic anemia, thrombocytopenia and severe acute kidney injury, so she was referred to our center was decided for evaluation by Nephrology and Hematology. In our institution, urinary sediment with dysmorphic erythrocytes was documented, peripheral blood smear without the presence of schistocytes, positive Coombs 4 crosses, renal ultrasound with data compatible with acute kidney injury, and supportive management with hemodialysis was initiated. Due to suspicion of autoimmune glomerulopathy, an autoantibody panel was indicated with negative antinuclear antibodies, anti-double-stranded DNA, anti-Sm, anti-B2 glycoproteins, and lupus anticoagulant, with normal complement values, stool culture, and negative stool Shiga protein assay, angiotomography of the abdomen where the integrity of renal circulation is verified, so renal biopsy with immunohistochemical study is performed, finding data compatible with thrombotic microangiopathy and acute tubulointerstitial nephritis. The patient is maintained with supportive care, steroids and hemodialysis as required with progressive recovery of renal function until renal replacement therapy is weaned, she is discharged with a steroid regimen and clinical nephrology and hematology follow-up. Conclusion Acute kidney injury is a complex and multifactorial entity, which requires a comprehensive approach in order to identify the best therapeutic option and to offer a better outcome in the renal function of these patients. The case of our patient presented a sudden deterioration of renal injury composed of two entities with different pathophysiology, demonstrating that, although the approach to these two entities converge in certain etiologies, it is imperative that the clinician does not forget the wide variety of factors that contribute to the development of renal injury.

The titers of antinuclear antibodies are associated with the degree of inflammation and organ damage in Primary Sjögren's Syndrome

Primary Sjögren’s Syndrome (pSS) falls within the category of connective tissue diseases, characterized by the presence of autoantibodies such as antinuclear antibodies (ANA). However, according to the classification criteria for pSS, some patients may exhibit a negative result for autoantibodies. Patients with a negative result for autoantibodies may lack typical features of connective tissue diseases, and the immunological state as well as the extent of organ involvement and damage may differ from those with positive autoantibodies. This study aims to compare the clinical phenotypes of patients with positive and negative autoantibodies, providing insights for disease classification and treatment selection for clinicians. Patients with pSS were grouped based on the presence and titers of their autoantibodies. Subsequently, differences in organ damage and laboratory indicators were compared between these groups, aiming to analyze the value of autoantibody titers in assessing the condition of pSS. (1) Patients with positive ANA exhibited elevated levels of inflammatory indicators, including ESR, IgG levels, lip gland biopsy pathology grade, and overall organ involvement, in comparison with patients with negative ANA (P < 0.05). Furthermore, ANA-positivity correlated with a higher occurrence of multi-organ damage, particularly affecting the skin, mucous membranes, and the hematological system (P < 0.05). (2) As ANA titers increased, patients demonstrated elevated levels of IgG and an escalation in organ involvement (P < 0.05). (3) Patients in the positive autoantibody group (positive for antinuclear antibodies, anti-SSA, or anti-SSB antibodies) had higher IgG levels compared to the negative group (P < 0.05). (4) Patients with positive anti-SSA and anti-SSB antibodies exhibited higher levels of inflammatory indicators and IgG compared to other patients (P < 0.05); however, no significant differences were observed in terms of organ involvement and organ damage. Patients with positive ANA in pSS typically exhibit higher levels of inflammation and an increased likelihood of experiencing multi-organ damage. Furthermore, as the ANA titers increase, both inflammation levels and the risk of multi-organ damage also escalate. Additionally, the presence of anti-SSA and anti-SSB antibodies may contribute to an elevated risk of increased inflammation levels, but does not increase the risk of organ damage.

Primary Immunodeficiency Disorders (PIDs) and its Rheumatologic Manifestations Mohammad Imnul Islam

The hallmark of Primary Immunodeficiency Disorders (PIDs) is increased susceptibility to recurrent infections, which are often poorly responsive to therapy, prolonged and life-threatening. The infections can involve bones and joints. PIDs may also predispose to allergic, autoimmune, autoinflammatory and malignant disorders. Arthritis is the most common rheumatological manifestation of PIDs. Recurrent septic arthritis, arthritis with increased susceptibility to infection, skeletal changes, autoimmune disease or systemic lupus erythematosus with negative antinuclear antibody (ANA) are the essential clinical clues that could be considered rheumatologic manifestations of PIDs. This is considerable concern that early detection of PIDs patients invariably improves the quality of life and life expectancy through the prompt implementation of appropriate medical intervention. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 82-85

Clinical Profile of Patients with Primary Sjögren's Syndrome with Non-Identified Antinuclear Autoantibodies.

Objectives-The aim of the present study was to characterize the clinical phenotype of patients with primary Sjögren's syndrome (pSS) with non-identified antinuclear antibodies (ANA) in comparison with that of patients with pSS with negative ANA, positive typical ANA (anti-Ro/SSA and/or La/SSB) and positive atypical ANA. Methods-We conducted an observational, retrospective monocentric study at the Erasme University Hospital (Brussels, Belgium). Two hundred and thirty-three patients fulfilling the 2002 American-European Consensus Group criteria for pSS were included in this study. The patients were subdivided according to their ANA profile and demographics. The clinical and biological data of each subgroup were compared. Moreover, the relationships between these data and the ANA profiles were determined by multiple correspondence analysis. Results-In our cohort, 42 patients (18%) presented a non-identified ANA-positive profile. No statistically significant difference could be observed between non-identified ANA patients and ANA-negative patients in terms of age and/or ESSDAI score at diagnosis. There were significantly more frequent articular manifestations, positive rheumatoid factor (RF), and the use of corticosteroids in anti-Ro/SSA-positive patients compared to ANA-negative (p ≤ 0.0001) and non-identified ANA-positive patients (p ≤ 0.01). However, a significantly higher proportion of RF positivity and corticosteroid treatment was observed in non-identified ANA-positive patients compared to ANA-negative patients (p < 0.05). Conclusions-For the first time to our knowledge, our study has characterized the clinical phenotype of patients with pSS with non-identified ANA at diagnosis. The non-identified ANA-positive patients featured mostly a clinical phenotype similar to that of the ANA-negative patients. On the other hand, the non-identified ANA-positive patients were mainly distinguished from the ANA-negative patients by a greater proportion of RF positivity and the need for corticosteroid use due to articular involvement.

A Case of Lupus-Like Nephritis in a Patient with a Negative Antinuclear Antibody (ANA)

A Case of Lupus-Like Nephritis in a Patient with a Negative Antinuclear Antibody (ANA)

#5034 ANCA ASSOCIATED VASCULITIS AFTER COVID-19

Abstract Background and Aims ANCA associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by inflammation of small and medium sized vessels. The three main types of AAV are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Similar pathways are involved mechanisms of disease involving COVID-19 and ANCA-associated vasculitis. For instance, neutrophil extracellular traps (NETs) are induced in both entities. Method We describe 3 cases reports of patients with ANCA associated vasculitis after COVID19. Results Case 1: A 46-year-old female patient was hospitalized in intensive care unit for COVID19 pneumonia. She has fever, cough and dyspnea. A few days before, the SARS-CoV-2 polymerase chain reaction(PCR) was positive on nasopharyngeal swab. She received high flu nasal canula. She presented a pneumo-renal syndrome with intra-alveolar hemorrhage and acute kidney injury. Chest scanner shows lesions on bilateral lung parenchyma, and an acute kidney injury (AKI) on admission. Urinalysis revealed an active sediment with dysmorphic erythrocytes and signifcant proteinuria. Renal function gradually deteriorated. So intermittent hemodialysis treatment was initiated. Serological evaluation showed negative antinuclear antibody, and anti-dsDNA, normal serum complements, and an elevated MPO. In kidney biopsy, pauci-immune necrotizing GN with cellular crescents was detected. The patient received pulse dose corticosteroids and subsequently, she was transitioned to oral prednisone. She underwent 2 sessions of plasmapheresis, which were stopped in the absence of confirmation of pulmonary involvement. She received cyclophosphamide during the hospitalization. While hematuria and proteinuria were persistant in the most recent urinalysis, the sCr level decreased to 159 µmol/L. In addition, she developed adrenal insufficiency after stopping corticosteroid therapy, requiring her to be put on Cortef. Case 2: A 63-year-old female patient with past medical history of hypertension, was hospitalized in intensive care unit for dyspnea and hemoptysis. A few months before, the SARS-CoV-2 polymerase chain reaction(PCR) was positive on nasopharyngeal swab. She received high flu nasal canula (HFNC). At this moment, she had acute kidney injury with a sCr level of 165µmol/L that was not explored. Currently she presented a pneumo-renal syndrome with a rapidly progressive glomerulonephritis and intra-alveolar hemorrhage. Renal function gradually deteriorated and peak sCr level of 308µmol/L. Chest scanner shows ground glass lesions of bilateral lung parenchyma, and hemoglobin at 4.9 g/dL. Urinalysis revealed an active sediment with dysmorphic erythrocytes and signifcant proteinuria. So intermittent hemodialysis treatment was initiated. The patient received pulse dose corticosteroids and subsequently, she was transitioned to oral prednisone. She received cyclophosphamide during the hospitalization. Serological evaluation showed negative antinuclear antibody, and anti-dsDNA, normal serum complements, and an elevated MPO. She underwent 6 sessions of plasmapheresis, for intra-alveolar hemorrhage. There was an improvement in respiratory and renal function Case 3: 57 years old, with a history of functional colopathy, covid infection 1 month before her hospitalization in nephrology department for kidney injury. Currently she presented a pneumo-renal syndrome with a rapidly progressive glomerulonephritis and intra-alveolar hemorrhage. Urinalysis revealed an active sediment with dysmorphic erythrocytes and signifcant proteinuria. Serological evaluation showed negative antinuclear antibody, and anti-dsDNA, normal serum complements, an elevated MPO and positive anti GBM. She was treated with plasmapheresis and cyclophosphamide. Conclusion SARS-CoV-2 infection can be a 'trigger factor' for vasculitis. ANCA-associated vasculitis should be kept in mind in patients who develop acute kidney injury after COVID-19.

A Case of Linear Scleroderma in a Young Child: A Diagnosis Easily Missed in Primary Care.

BACKGROUND This case illustrates the challenges in diagnosing linear scleroderma (LS) in a child who presented to a primary care setting. Diagnosis of LS is easily missed due to the lack of prominent symptoms, subtle visible skin changes, and under-recognition of this condition. CASE REPORT A 7-year-old boy presented with a linear, painless, non-itchy rash at the center of his forehead, which has been present for 6 months. The rash extends vertically from the hairline to the bridge of the nose. The color gradually evolved from reddish to purplish-grey and shiny within 3 months. He had underlying eczema, allergic rhinitis, and allergic conjunctivitis since birth. His condition remained unrecognized despite consultations with various medical specialties, including family medicine specialist, ophthalmologist, otorhinolaryngologist, and a general pediatrician. Six months after the onset of his lesion, he was subsequently referred to a pediatric dermatologist and pediatric rheumatologist, who made the diagnosis of LS. Laboratory investigations for autoimmune disease showed that negative antinuclear antibodies (ANA) and inflammatory markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were normal. Skin biopsy provided a tissue confirmation of the diagnosis. MRI of the lesion showed no extension into the underlying muscle or bone erosions. The patient was initially treated with intravenous (IV) methylprednisolone for 3 days, followed by oral methotrexate weekly and prednisolone. The lesion improved after 1 month of treatment, and after 15 months it was less pigmented and less noticeable. CONCLUSIONS LS is the commonest form of localized scleroderma in children. LS on the forehead can erode into the underlying tissues and is sometimes associated with extensive hemifacial atrophy. Treatment should be instituted early to prevent late irreversible fibrotic sequelae. This report aims to highlight the importance of early diagnosis and treatment of an uncommon but potentially disfiguring condition.

Negative ANA-IIF in SLE patients: what is beyond?

The antinuclear antibody (ANA) test has high sensitivity in diagnosing and classifying systemic lupus erythematosus (SLE).ObjectivesTo describe the immunological pattern of SLE patients through investigating specific antinuclear autoantibodies by enzyme dot immunoassay and studying their frequency in both positive and negative ANA indirect immunofluorescence assay (IIF) cases.MethodsIn a cross-sectional study, blood samples from 393 newly diagnosed SLE patients were analyzed using (IIF) on HEp-2 cells and ANA dot immunoassay by automated enzyme immunoassay (EIA) to detect 19 antibodies.ResultsNinety-one percent of the patients are females; their mean age was 37 ± 12.28. Antinuclear antibody (ANA) was detected by IIF in 82.4% of cases, with 181 (46.1%) speckled and 167 (42.4%) homogeneous ANA patterns. The majority of patients (96%) demonstrated autoantibodies via EIA. Among the ANA-IIF-negative patients, 97.2% demonstrated autoantibodies. There was a significant difference in the frequency of certain autoantibodies between SLE patients with negative and positive ANA-IIF (1.44 0.73, 3.12 2.09, p = 0.00) respectively.ConclusionThe results of analyzing 19 autoantibodies with the ANA staining pattern increased the significance of analyzing the immune profile even if IIF is negative when clinical symptoms strongly suggest SLE diagnosis. Certain autoantibodies may evade staining by the IFA approach while they are present in the patient’s serum, and they may not be detected by the ANA EIA profile if it does not contain that antigenic substrate.Key Points• Indirect immunofluorescence on Hep-2 is the conventional method for ANA detection and is regarded as the “gold standard” for testing in clinical practice for SLE.• In our study, ANA profile dot enzyme immunoassay (EIA)-based test was performed to evaluate 19 autoantibodies in SLE patients either positive or negative for ANA-IIF.• The presence of anti-dsDNA with ANA-IIF-negative serum in 32.4% of SLE patients provides evidence that not all anti-dsDNA antibodies are identified on standard HEp-2 substrates.• certain autoantibodies can evade staining by the ANA-IIF method despite being present in the SLE patient’s blood; this supports the ANA profile enzyme dot immunoassay as a more sensitive test.

Clinical and Laboratory Evaluation of Acute Pericarditis Associated with Antinuclear Antibodies Positivity.

Up to 30% of patients with acute pericarditis develop recurrent pericarditis. Acute pericarditis may be a manifestation of an underlying systemic autoimmune disease. Therefore, we evaluated the characteristics of patients with acute pericarditis according to antinuclear antibodies (ANA) positivity/negativity. Participants with acute pericarditis and negative ANA (n=29), recurrent pericarditis with positive ANA (n=30) and healthy controls (n=11) were examined. The groups were compared using serum parameters (ANA, C-reactive protein, leucocyte count, erythrocyte sedimentation rate, total antioxidant status, nitric oxide (NO), and oxidative stress index (OSI)) and imaging techniques (electrocardiogram, echocardiography, cardiovascular magnetic resonance, and venous Doppler ultrasound). In females, acute pericarditis associated with ANA occurred more frequently (p<0.001). ANApositive acute pericarditis had significantly lower NO and OSI (p<0.05 and p<0.001, respectively) and pericardial inflammation on magnetic resonance. We found a pulmonary embolism in one patient with positive ANA. Slow venous flow (SVF) occurred more often in acute pericarditis associated with ANA than in the ANA-negative group on venous ultrasound (p<0.05). The prevalence of positive ANAs was 1.6 times higher among SVF patients than in controls. This study suggests that acute pericarditis associated with ANA is more common in middle- aged females. SVF and lower oxidative stress tests were more common in patients with ANAassociated acute pericarditis. Acute pericarditis associated with ANA could be considered as a hypercoagulable state. Therefore, all newly diagnosed pericarditis patients (especially females) should be checked for ANA positivity. Awareness of this coexistence should be promptly addressed to establish management strategies.

Raynaud's Phenomenon: A Brush Up!

Raynaud's Phenomenon: A Brush Up!

Do Antinuclear Antibodies Influence the Clinical Features of Chronic Spontaneous Urticaria?: A Retrospective Cohort Study.

Antinuclear antibody (ANA) is often used as a screening test for autoimmune comorbidities in patients with chronic spontaneous urticaria (CSU). However, the relationship of ANA status and the clinical course of the disease have not been fully described. To compare clinical features of CSU patients who are positive and negative for ANA. This was a retrospective cohort study that enrolled CSU patients attending the Urticaria Clinic at Siriraj Hospital from 2013 to 2019. Demographics, clinical characteristics, laboratory investigations, and treatments were collected until July 2021. All patients were investigated for ANA. Clinical feature data was compared between CSU patients with positive ANA and negative ANA groups using the 2-sample t-test and the Mann-Whitney U test for quantitative variables. The chi-squared test or Fisher's exact test was conducted to explore the association of qualitative variables. Disease relapse and remission were analysed via Kaplan-Meier survival analysis. Of 323 CSU patients, 31% had positive ANA. There were no significant differences in disease severity or impairment in quality of life. Patients with a positive ANA test had significantly lower prevalence of allergic rhinitis (p = .048) and significantly higher level of erythrocyte sedimentation rate (p = 0.007). Kaplan-Meier survival analysis showed that 2% of ANA positive CSU patients achieved remission status after one year and 28% did so after five years. There was no statistically significant difference in time to remission and time to relapse between ANA-positive and negative groups. Positive ANA in CSU patients could not indicate the differences in main disease characteristics from the ANA-negative CSU patients. Investigation for ANA may be useful in CSU patients who are suspected of having autoimmune diseases.

A retrospective study of prevalence and pattern of international consensus on ANA patterns among patients with hepatitis C virus infection.

BackgroundA previous study reported a 30% prevalence of various autoantibodies among patients with hepatitis C virus (HCV) infection. The International Consensus on Anti-Nuclear Antibody (ANA) Patterns was recently introduced to classify ANA patterns based on immunoassay on HEp-2 cells. There is no previous report with this newly developed classification to evaluate patients with HCV infection. The study aims to study the prevalence and pattern of ANA patterns among HCV-infected patients.MethodsWe retrospectively analyzed the medical records of patients with HCV infection from September 2020 to June 2021 at our institution. A positive ANA is defined as a titer of more than 1:320. We compared patient features among the positive and negative groups.ResultsOverall, 258 patients were enrolled—184 patients with negative ANA and 74 patients (28.7%) with positive ANA. The mean age was 67.3 in ANA positive group and 61.2 ANA negative group. Female was prominent with ANA positive and accounted for 63.5%. The most detected ANA pattern was AC-1(homogeneous) (25.9%), followed by AC-4(fine speckled) (25.2%) and AC-21(anti-mitochondrial antibody) (9.6%). In ANA positive group, we found a trend of lower HCV viral load (5.72 log10 IU/ML vs. 6.02 log10 IU/ML), lower alanine aminotransferase level (39.5 U/L vs. 44 U/L), and higher advanced fibrosis (F3 and F4) (38.5% vs. 26.1%). In addition, higher positive ANA (more than 1:640) is significantly associated with lower estimated glomerular filtration rate (eGFR) (77.76 vs. 87.94 mL/min/1.73 m2, P = 0.044).ConclusionsA high prevalence (28.7%) of ANA was found in patients with chronic hepatitis C. The presence of positive ANA is not related to the severity of their hepatic manifestation. However, higher positive ANA was significantly associated with lower eGFR.

S3159 Skin as Yellow as Turmeric: A Case Report on Turmeric-Induced Liver Injury

Introduction: Turmeric has been used for centuries, in food and as a medical remedy. It generally has a good safety profile, however over-the-counter and online available turmeric herbal and dietary supplement (HDS) have been recently implicated in Drug Induced Acute Liver Injury (DILI). Case Description/Methods: A 63 year old woman was admitted for worsening jaundice for two weeks. On admission total bilirubin was 20.9mg/dL, direct bilirubin 12.1mg/dl, AST 1987 IU/L, ALT 2075 IU/L, Alkaline phosphatase (ALKP) 285 IU/L, INR 0.96, normal albumin and platelets levels. Meld-Na score was calculated to be 24. Ultrasound of liver and CT scan of abdomen did not show any hepatic or biliary abnormality. Viral hepatitis serology was negative. Auto-immune hepatitis was ruled out with negative anti-nuclear antibody (ANA), anti-smooth muscle (ASM) and anti-mitochondrial antibodies and there was no hypergammaglobulinemia. Patient denied drinking alcohol or using any other medication. She reported consuming daily Turmeric dietary supplements 6 weeks ago. Liver biopsy reveled minimal portal chronic inflammation, but no lobular inflammation/necrosis, fibrosis or plasma cell infiltration- suggesting in favor of drug induced liver injury and against autoimmune hepatitis (AIH). Turmeric was discontinued and liver enzymes gradually trended down in next few weeks. Discussion: Turmeric has been used for centuries in food and recently is available over-the-counter and online as herbal dietary supplements (HDS). It is also used as herbal remedy for arthritis, digestive diseases etcetera for its anti-inflammatory and anti-oxidant properties. It is hypothesized that Turmeric supplements available online often contain piperine or nanoparticle delivery methods that increase its bioavailability resulting in DILI. It can occur from few weeks to months after initiation of drug. Some patient may develop drug induced autoimmune hepatitis (DI-AIH) with positive autoantibodies, however in this patient negative autoantibodies, imaging studies and liver biopsy, ruled out all other possible causes of liver injury. Roussel-Uclaf Causality Assessment Method (RUCAM) score can be used for causality assessment in DILI. RUCAM score was 9 in this case which means ‘high probability’ that Turmeric was the cause of DILI.

S3081 Newfound Glow: The First Reported Case of Drug-Induced Liver Injury Due to Tofacitinib

Introduction: Tofacitinib, a Janus kinase (JAK) inhibitor, is a medication used to treat autoinflammatory conditions. It has previously been associated with mild hepatocellular liver enzyme elevations, but here we describe the first reported case of a clinically apparent drug-induced liver injury (DILI) related to tofacitinib. Case Description/Methods: A 29-year-old man with ulcerative colitis developed jaundice, malaise, anorexia, abdominal pain, diarrhea, and pruritus six months after starting tofacitinib. His only other medication was lisinopril. He consumes less than three alcoholic drinks weekly. Liver chemistries revealed aspartate aminotransferase (AST) 635 IU/L, alanine aminotransferase (ALT) 614 IU/L, alkaline phosphatase (ALP) 150 IU/L, total bilirubin (T-Bili) 3.2 mg/dL, and direct bilirubin (D-Bili) 1.7 mg/dL. Coagulation studies were normal. Abdominal ultrasound showed a diffusely hypoechoic liver and a diffusely thickened gallbladder wall but no biliary pathology. He stopped taking tofacitinib, and his liver chemistries peaked at AST 826 IU/L, ALT 1427 IU/L, ALP 182 IU/L, and T-Bili 6.5 mg/dL. Anti-smooth muscle antibody was slightly positive at 41. Additional workup included negative antinuclear antibody and negative serologies for cytomegalovirus, Epstein-Barr virus, and hepatitis A, B, and C. His symptoms improved, and he resumed tofacitinib two months after symptom onset. Four months later, the patient’s symptoms recurred and labs redemonstrated acute liver injury with a new peak of T-Bili 9.1 mg/dL. Liver biopsy revealed acute hepatitis with diffuse severe hepatocanalicular cholestasis, inflammation, and necrosis, consistent with DILI. He stopped taking tofacitinib, and after one month his symptoms resolved and liver chemistries normalized. He was transitioned to vedolizumab and has remained asymptomatic. (Figure) Discussion: This patient developed a clinically apparent liver injury with jaundice six months after initiating therapy with tofacitinib for ulcerative colitis. Other causes, such as viral hepatitis, alcohol-related liver disease, and autoimmune hepatitis, were ruled out. Biopsy results were consistent with DILI, and he was on no other culprit medications. He was rechallenged with tofacitinib and redeveloped liver injury, strongly supporting the diagnosis of tofacitinib-induced DILI. The mechanism of liver injury is not fully understood but might be attributed to drug metabolism via CYP3A4. More research should be conducted to better elucidate the mechanism of liver injury by tofacitinib.Figure 1.: Liver biopsy with acute hepatitis, severe hepatocanalicular cholestasis, inflammation, and necrosis, as well as a multinucleated hepatocyte, consistent with drug-induced liver injury in the setting of tofacitinib use.

P40 Dry eyes and a dry mouth: is it Sjögren’s syndrome?

P40 Dry eyes and a dry mouth: is it Sjögren’s syndrome?

P37 A rare cause of autoimmune hepatitis secondary to a biological therapy

P37 A rare cause of autoimmune hepatitis secondary to a biological therapy

Clinical significance of autoantibodies against ubiquitin carboxyl hydrolase L1 epitopes in the screening and diagnosis of Sjögren syndrome

Objective: To study the clinical significance of autoantibodies against different ubiquitin carboxyl hydrolase L1 (UCH-L1) epitopes in Sjogren syndrome (SS). Methods: The serum levels of different UCH-L1 epitope autoantibodies in 98 SS patients [SS group, 17 males and 81 females, aged (49.1±12.3) years] in the Fifth Affiliated Hospital of Zhengzhou University and Peking University People's Hospital from January 2017 to January 2020 and 37 healthy controls [control group, 6 males and 31 females, aged (46.3±5.8) years] were determined by enzyme-linked immunosorbent assay (ELISA). Three potential epitopes of UCH-L1 protein were analyzed and synthesized and anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies were studied between the two groups. The levels of the two anti-UCH-L1 antibodies in the two groups were compared. The correlation between the levels of UCH-L1 antibodies and clinical data of SS patients were analyzed by Pearson correlation analysis. Results: The serum levels of anti-UCH-L1203-214 and anti-UCH-L158-69 antibody in SS patients were significantly higher than those in healthy controls (HCs) (anti-UCH-L1203-214: 108.2±54.3 vs 78.9±25.8, P<0.001, anti-UCH-L158-69: 86.8±33.3 vs 60.4±21.5, P<0.001). The positive rates of anti-UCH-L1203-214 and anti-UCH-L158-69 antibodies in serums of SS patients were 27.6 % (27/98) and 25.5% (25/98), and those in HCs were 2.7%(1/37) and 5.4 %(2/37), respectively. In SS patients with positive serum anti-UCH-L158-69 antibody, the levels of IgG, γ globulin and rheumatoid factor (RF) and anti-SS-related antigen B (anti-SSB) antibody positive rate were all significantly higher than those in patients with negative antibody (all P<0.05). In SS patients with negative antinuclear antibody (ANA), anti-RNA binding protein (anti-RNP) antibody, anti-SS-related antigen A (anti-SSA) antibody and anti-SSB antibody, the positive rates of anti-UCH-L1203-214 antibody was 32.1%(9/28), 27.2%(25/92), 36.4%(12/33), 28.6%(18/63), respectively; and the positive rates of anti-UCH-L158-69 antibody was 21.4%(6/28), 30.4%(28/92), 30.3%(10/33), 20.6%(13/63), respectively. The level of serum anti-UCH-L1203-214 antibody in SS patients was positively correlated with the IgA level (r=0.21, P=0.024). The level of anti-UCH-L158-69 antibody in SS patients was positively correlated with the levels of γ-globulin, IgG and RF (r=0.35, 0.33, 0.32, all P<0.01). Conclusion: Autoantibodies against UCH-L1 epitopes are correlated with some clinical parameters of SS patients, which is of promising significance in the screening and diagnosis of SS.

Expanded assessment of xenobiotic associations with antinuclear antibodies in the United States, 1988-2012.

The prevalence of autoimmunity in the U.S. has increased recently for undetermined reasons. Little is known about associations between autoimmunity and environmental causes. In a large representative sample of the U.S. population, we expanded our prior exploratory study of how exposures to selected xenobiotics and dioxin-like (DL) mixtures relate to antinuclear antibodies (ANA), the most common biomarker of autoimmunity. We analyzed cross-sectional data on 12,058 participants aged≥12years from three time periods of the National Health and Nutrition Examination Survey between 1988 and 2012, of whom 14% were ANA-positive. We used lognormal regression models and censored-data methods to estimate ANA associations with xenobiotic concentrations overall and in sex, age, and race/ethnicity subgroups. Our analyses adjusted for potential confounders and appropriately handled concentrations below detection limits. Observed ANA associations were positive for most DL compounds and nonDL polychlorinated biphenyls (PCBs), negative for most phthalates, and mixed for other xenobiotic classes. After correcting for multiple comparisons, some associations remained statistically significant. In subgroup analyses, the most significant finding was a positive ANA association with N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (MHB2) in males, followed by positive associations with 2,2',3,5'-tetrachlorobiphenyl (PCB 44), 2,2',4,5'-tetrachlorobiphenyl (PCB 49), and 2,2',3,4',5',6-hexachlorobiphenyl (PCB 149) in 12-19year-olds, and with 3,4,4',5-tetrachlorobiphenyl (PCB 81), 2,2',3,3',4,4',5,5',6-nonachlorobiphenyl (PCB 206), and N-acetyl-S-(phenyl)-L-cysteine (PMA) in Mexican Americans. Negative associations were found with mono-benzyl phthalate (MBzP) in 20-49year-olds and mono-n-butyl phthalate (MnBP) in 12-19year-olds. In overall analyses, combining stratum-specific results across race/ethnicity strata revealed a positive ANA association with PCB 81 and a negative ANA association with N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA). This study identified potential associations between ANA and various xenobiotics. Further investigation to confirm these observations and elucidate effects of certain xenobiotics on immune regulation could have important mechanistic, preventive, and treatment implications for a variety of immune-mediated disorders.

Systemic sclerosis patients with negative antinuclear antibodies have distinctive clinical manifestations: amulticenter CRDC cohort in China.

The presence of circulating antinuclear antibodies (ANAs) is ahallmark of immune dysregulation in patients with systemic sclerosis (SSc). Avariety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in aChinese Rheumatism Data Center (CRDC) multicenter cohort in China. Patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs. Antinuclear antibodies were detected in 2129 of 2809patients enrolled in the study; 4.2% of patients were negative. There were more males among ANA-negative SSc patients (29/60 vs. 294/1746, p < 0.001). The incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs. 18.5%, p = 0.002), interstitial lung disease (65.2% vs. 77.9%, p = 0.015), and pulmonary arterial hypertension (11.5% vs. 29.0%, p = 0.006) was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal erythrocyte sedimentation rate (32.4% vs. 47.6%, p = 0.013) and IgG elevation (14.3% vs. 37.0%, p = 0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients. Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.