anti-Ro Research Articles

CASE OF REFRACTORY INTERSTITIAL LUNG DISEASE IN ANTISYNTHETASE SYNDROME

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Along with corticosteroids, patients with anti-synthetase syndrome associated interstitial lung disease (ILD) require a corticosteroid-sparing agent, such as azathioprine, rituximab, or cyclophosphamide. However, there is no study that demonstrates the superiority of one agent, making it difficult to choose one over the other given their high side effect profile. CASE PRESENTATION: A 67 years old female who had symptoms of left shoulder, arms, and eye pain that started 5 months ago, and dyspnea with exertion that started 7 months prior to presenting with worsening dyspnea. Initial work up was significant for elevated CK and aldolase, and positive ANA, anti Jo-1 and anti SS-A. CT was significant for NSIP pattern; and workup for infection was negative. Her initial oxygen requirement was 6 L. She was started on prednisone 60 mg daily, but her dyspnea progressed, getting into respiratory failure that required intubation. She was switched from prednisone to methylprednisolone 1 g/day for 3 days. She also received 2 doses of IV cyclophosphamide 1000 mg, followed by a total of 3 doses of IV Rituximab 700 mg that was initiated 8 days later. She was extubated 6 days later to facemask ventilation. She had frequent episodes of worsening dyspnea that occurred after a corticosteroid tapering attempt, therefore, requiring increased corticosteroids. She was eventually weaned to 2 liters of oxygen and discharged with home oxygen and a tapered dose of prednisone. DISCUSSION: Anti-synthetase syndrome is part of the idiopathic inflammatory myopathies (IIM) in which antibodies develop against aminoacyl tRNA. The diagnostic criteria for antisynthetase syndrome is the presence of tRNA synthetase autoantibody in addition to clinical features, such as ILD and/or myositis. The most commonly identified antibody is anti-Jo-1; other less common antibodies include: anti-PL12 and anti-PL7. ILD Anti-synthetase syndrome is more severe, rapidly progressing and leads to a high mortality when compared to ILD in the other IIMs. Corticosteroid-monotherapy in these patients is known to cause frequent lung disease reoccurrence. Therefore, an additional agent needs to be added in refractory cases. Azathioprine is a commonly used agent in conjunction with prednisone, but not well studied. Multiple other case studies showed improvement in lung function and/or pulmonary symptoms in patients who received Rituximab as the adjunctive medication. The treatment options that can be used in antisynthetase ILD lies at the discretion of the physician. In our case, the use of corticosteroids, Rituximab, and cyclophosphamide appeared to have significant clinical outcome. CONCLUSIONS: To better treat patients with this condition, high clinical suspicion is needed, and patients may benefit from early rituximab therapy. Future studies that compare the effect of corticosteroid-sparing agents would help on deciding the best treatment agents. Reference #1: Witt L., Curran J., Strek M. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016 Sep; 23(5): 218-226. DISCLOSURES: no disclosure on file for Subramanyam Chittivelu; No relevant relationships by Ronald Espinosa, source=Web Response No relevant relationships by Abdirahman Hussein, source=Admin input

EP32 Gastroparesis in Sjögren’s syndrome

EP32 Gastroparesis in Sjögren’s syndrome

O14 Transitions in diagnosis and between services in juvenile idiopathic arthritis: living and learning

O14 Transitions in diagnosis and between services in juvenile idiopathic arthritis: living and learning

EP30 Sensory ganglionopathy as a possible presenting feature of Sjögren’s syndrome

Case report - IntroductionPrimary Sjögren’s syndrome is a systemic autoimmune disease affecting the exocrine glands, commonly resulting in dryness of mouth and eyes. It can also rarely present with neurological symptoms most commonly peripheral neuropathies. The case highlights a rare case of sensory and motor neuropathy with some features suggestive of Sjögren’s syndrome as an underlying diagnosis.Case report - Case descriptionA 54-year-old Caucasian lady was transferred from a local hospital for specialist neurology care. She described widespread paraesthesia over two months progressing to lower limb weakness worsening over a two-day period. Her symptoms further progressed to involve her arms and new blurred vision. On further questioning she reported previous severe mouth ulcers, possible genital ulcers and painful jaw swelling with long standing history of dry mouth. On thorough neurological examination, the positive findings were mild ptosis of the right eye, paraesthesia on palpation of face, upper limbs had a flaccid tone with reduced power and pseudoathetosis of outstretched arms, reduced proprioception, and absent reflexes. Lower limbs were more affected with worse power and absent proprioception. Schirmer’s test showed normal tear production but saliva production was reduced.MRI brain and spine were reported as pathological enhancement in both optic nerves, no obvious brain parenchymal abnormality, no obvious spinal cord abnormality. Lumbar puncture CSF pro 0.38, white cells 12 (poly 50%, mono 50%), red cells 3700, no organisms on gram stain, opening pressure 21.5 cmH2O. Sural nerve biopsy demonstrated profound loss of sensory axons, severe loss of large myelinated fibres in all fascicles with motor nerve involvement. Muscle biopsy demonstrated chronic neurogenic atrophy. Rheumatology screen showed positive anti Ro 52 antibodies (on an extended myositis screen). EMG demonstrated neurophysiological evidence of widespread marked loss of sensory axons in the upper and lower limbs and partial loss of motor axons in several lower limb territories. USS parotid glands showed some possibly mildly abnormal areas, minor salivary gland biopsy was normal. She received methylprednisolone, IV immunoglobulin and two courses of plasma exchange. Given some improvement following this treatment, further immunosuppression was felt to be appropriate. Initially Mycofenolate mofetil was started and Rituximab is now being considered.Case report - DiscussionThis case demonstrates a mixed neuropathy picture. Following thorough investigations, many differential diagnoses of mixed neuropathy were considered and excluded (e.g. Guillain Barre, Syphilis, MS, HIV, Hepatitis). Neurological symptoms can develop before the onset of sicca symptoms in Sjögren’s syndrome. With a positive Anti Ro52, xerostomia and clinical improvement with methylprednisolone and plasmaphereses it seems likely there is an underlying autoimmune diagnosis in this case and despite a normal biopsy she would meet the 2016 ACR/EULAR classification criteria for Sjögren’s syndrome.Case report - Key learning pointsSjögren’s syndrome should be considered as a potential underlying cause in patients with a sensory ganglionopathy.Neurological symptoms can develop before the onset of sicca symptoms in Sjögren’s syndrome.

PRIMARY SJOGREN SYNDROME CAUSING PULMONARY EXTRANODAL MARGINAL CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extranodal marginal zone lymphoma (MZL) of the lung is a rare pulmonary lymphoid malignancy and World Health Organization (WHO) classifies Mucosa associated lymphoid tissue (MALT) lymphoma as a subtype of B-cell MZL. CASE PRESENTATION: 80 year old Caucasian male with past medical history of obstructive sleep apnea, chronic kidney disease stage III, type II diabetes mellitus, hypertension and tobacco abuse, was first seen in pulmonary clinic for asymptomatic innumerate bilateral pulmonary nodules noted on Computed Tomography (CT) scan of the chest. He complained of occasional chronic dry mouth on further questioning. Antibody testing was positive for Antinuclear antibodies (245 AU/ml) and SS Ro antibody (188 AU/ml). His dry mouth and lower lobe predominant cystic and nodular changes were concerning for lymphoid interstitial pneumonia associated with Sjogren's syndrome. He was referred to rheumatology then subsequently lost to follow up. He presented two years later with increased shortness of breath and progressive weight loss. Pulmonary function tests (PFTs) showed an isolated low diffusing capacity for carbon monoxide at 33% predicted (down from 75% prior). CT scan revealed progression of his bilateral lung nodules and cystic changes in the lower lungs bilaterally. He then underwent bronchoscopy and surgical lung biopsy. This showed a low-grade B- cell lymphoma with plasmacytic differentiation, most consistent with MALT stage 1E Extranodal marginal zone lymphoma. Patient was started on rituximab weekly for 4 weeks and reported some improvement in his sicca symptoms. DISCUSSION: Roughly 10 to 20 percent of SS patients have clinically significant lung disease defined by symptoms most commonly cough and dyspnea. Abnormal imaging and PFTs are common. Thin-walled lung cysts are detected with CT imaging in 12 to 46 percent of SS patients. Interstitial lung disease can occur in SS in several forms (1). In a series of thirteen patients with pulmonary MALT lymphoma performed by Yachoui et. al, 54% were positive for primary sjogren syndrome (PSS) (2). No difference in outcomes was noted on two large retrospectives studies involving different treatment modalities including surgery, chemotherapy or combined therapy. Asymptomatic patients should be observed with no treatment indicated initially. It is indicated for patients with a high burden of lymphadenopathy with splenomegaly, organ dysfunction, bone marrow suppression, and/or rapid disease progression (3). Series performed by Yachoui et. al demonstrated a favorable prognosis in all cases of pulmonary MALT lymphoma with all treatment modalities resulting in complete and sustained response (2). CONCLUSIONS: SS can have wide ranging organ involvement. Prompt referral to rheumatology and active monitoring is paramount. Further investigation is warranted to better understand pulmonary MALT pathogenesis, treatment, and outcomes in PSS. Reference #1: Stojan, G., et al. (2013). “Pulmonary manifestations of Sjögren's syndrome.” Current allergy and asthma reports 13(4): 354-360. Reference #2: Yachoui R, Leon C, Sitwala K, Kreidy M. Pulmonary MALT lymphoma in patients with Sjögren's syndrome. Clinical medicine & research. 2017;15(1-2):6-12. Reference #3: Pinotti G, Zucca E, Roggero E, Pascarella A, Bertoni F, Savio A, et al. Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma. Leukemia & lymphoma. 1997;26(5-6):527-37

The Analysis of Clinical Features of Systemic Lupus Erythematosus (SLE) in Children

Objective: Observe the clinical characteristics of children with SLE, namely, to observe the symptoms and laboratory examinations, such as blood routine, blood lipid, immunoglobulin, complement, autoantibodies, serum 25 (OH) D and other indicators, and to explore the clinical characteristics, the difference and the significance of vitamin D supplements between male and female SLE patients in children respectively. Methods: We enrolled 64 cases of SLE patients in children who were admitted into the department of pediatrics and rheumatology of the third affiliated hospital of sun yat-sen university in guangzhou from May 1, 2011 to February 1, 2019, They were analyzed retrospectively, adopting ?² test for statistical analysis. Results: 64 cases of SLE in children, which included 10 cases of male and 54 cases of female. Clinical manifestations: facial skin rash in 48 patients (75%), fever in 38 cases (59.4%), arthritis in 28 cases (43.8%), oral ulcer in 18 cases (28.1%), serositis in13 cases (20.3%), and the sun allergy in 9 cases (14.1%), the damage of central nervous system in 7 cases (10.9%) . Laboratory examination: 30 cases of leukopenia (46.9%), anemia in 30 cases (46.9%), thrombocytopenia in 12 cases (18.8%), hematuria in 18 cases (28.1%), proteinuria in 33 cases (51.2%), 6 patients with renal impairment (9.4%), antinuclear antibody positive in 63 cases (98.4%), anti-double-stranded DNA (dsDNA) antibody positive in 48 cases (75%), anti SSA antibody positive in 44 cases (68.7%), SSB antibody positive in 33 cases (51.6%), Sm antibody positive in 40 cases (62.5%), nucleosome antibody positive in 28 cases (43.8%) .Among these children, male SLE patients were higher than female children with SLE in the damage of kidney, Sm antibodies and resisting nucleosome antibody positive rates (?²= 4.451, 8.336, 6.803, P<0.05), the female children with SLE was higher than male SLE Children in the anti-SSB antibody positive rate (?²=4.945, P < 0.05). In 64 cases of SLE children, which included 52 cases were lower than the normal level of serum 25 (OH) D measurements, 12 cases were in the normal lower limit of serum 25 (OH) D measurements, at the same time, the female SLE. Patients was higher than male children with SLE in the reduce rate of serum 25 (OH) D (?²= 8.351, P < 0.05). Conclusion: Male SLE patients which appeared damage of kidney easier than female patients , the proteinuria was the most common in the damage of kidney. Resistance to Sm antibodies which was the risk factor of renal injury with higher incidence in male children with SLE; Anti nucleosome antibody which was the risk factor for the disease activity in male children with SLE were higher than female children with SLE. It was estimated that the risk of Sjogren's syndrome appeared in female with SLE were higher than that in male SLE children. In this retrospective study, the serum 25 (OH) D levels were significantly lower in children with SLE, and vitamin D supplementation was required.

Anti-Ro52 antibodies in clinical practice: A single-centre experience.

To analyse the clinical significance of anti-Ro52 autoantibodies that target TRIM21 protein and occur in a variety of connective tissue diseases (CTD), 4782 cases with blood tested positive for anti-Ro52 antibodies between January 2016 and September 2017 in Drum Tower Hospital were enrolled. Anti-Ro52 and anti-Ro60 were measured using the immunoblotting method together with antibodies against other extractable nuclear antigens at the time of the patient's first visit. In this cohort, females accounted for the majority of all subjects (75.9%) and the average age was 47.25years old. About 97.4% were diagnosed as having various diseases, in which around 2/3 were CTDs. The incidence of CTD in patients with merely anti-Ro52 was lower than those with both anti-Ro52 and anti-Ro60 (54.7% vs 85.5% for all patients and 53.3% vs 87.1% for inpatients, both P<.0001). Amongst CTDs, the incidence of systemic lupus erythematosus was significantly decreased, while the incidence of inflammatory myositis as well as undifferentiated connective tissue diseases was increased in anti-Ro52 single-positive group. For patients with either CTDs or non-CTDs, respiratory involvement was more common in patients with merely anti-Ro52 (67.6% vs 34.7%, P<.0001 and 53.2% vs 36.3%, P<.01). Sub-analysis revealed that both interstitial lung disease and pulmonary infection were related to anti-Ro52 in CTD inpatients (P<.0001 and P<.05). Our study shows that anti-Ro52 could occur in various clinical conditions. These antibodies may appear in the early stage of CTD with the lung an important target organ, thus their presence warrants long-term follow-up.

Anti-Ro52 antibody is an independent risk factor for interstitial lung disease in dermatomyositis

AimRecent studies have shown that anti-Ro52 antibody is associated with both interstitial lung disease (ILD) and the degree of disease severity in juvenile patients with dermatomyositis (DM). We found that more than half of adult patients with DM were positive for anti-Ro52 antibody. In this study, we analysed the correlation between anti-Ro52 antibody and ILD in adult patients with DM. MethodSerum samples were collected from 153 adult inpatients with DM, at the First Medical Centre of PLA General Hospital, Beijing, China, who met the classification criteria of idiopathic inflammatory myopathies from March 1, 2016 to September 30, 2019. The patients were followed up to May 31, 2020. Immunoblotting was used to detect 16 types of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) from serum samples. High-resolution computed tomography (HRCT) was used to calculate the ILD score, and tumours were screened. Clinical data and HRCT scores were evaluated and analysed retrospectively. ResultsOur results showed that anti-Ro52 antibodies were the most commonly found antibodies in patients with DM, with a positive rate of 52.9%. Anti-Ro52, anti-aminoacyl-tRNA synthetase (anti-ARS), and anti-melanoma differentiation-related gene 5 (anti-MDA5) antibodies were found to be risk factors for ILD development. Anti-Ro52 antibodies had a strong predictive effect on ILD in patients with DM. ConclusionThe occurrence of ILD is highly likely in patients with DM who are positive for the anti-Ro52 antibodies. Thus, anti-Ro52 antibodies is an independent risk factor for ILD in patients with DM.

Puntaje de tinción ocular en pacientes con diagnóstico de síndrome de Sjögren en una institución de salud en Medellín, Colombia

IntroductionSjögren's syndrome is an autoimmune disease associated with multiple genetic and environmental factors. It mainly affects the salivary and lacrimal glands with cellular infiltration leading to dry eye symptoms, with keratoconjunctivitis sicca and its complications often being described. Its classification criteria have changed over the years, due to the diversity in the organs involved and clinical spectrum of the disease. Today, there are clinical and para-clinical parameters for its identification. One of these is the ocular staining score (OSS), standardised from the SICCA cohort. ObjectiveTo describe the findings in the ocular evaluation, the results of the tests of the OSS, and the clinical characteristics of the classification criteria in patients with Sjögren syndrome in the outpatient service of Rheumatology Outpatient Department a university hospital in north-western Colombia. MethodsAn observational, descriptive, cross-sectional study was conducted. The characteristics of the Sjögren syndrome classification criteria were described, including the OSS score for one year. Clinical tests and standardised ocular stains were performed, evaluating characteristics of the ocular surface, tear production, and lissamine green and fluorescein stains on the conjunctiva and cornea, assigning, according to the findings, a score to each parameter in order to assess positivity according to the classification standard. The qualitative variables were expressed by means of absolute and relative frequencies, and the quantitative ones as the median and interquartile range (P25-P75), according to the distribution of the data. Epidat statistical package, version 4.2, was used. ResultsA total of 28 patients were included. Dry eye symptoms were present in 89.2%, 96.4% had positive findings in the eye examination, and 78.5% had a score on the OSS according to the classification criteria. The median OSS was 6.14, and anti-Ro antibodies were positive in 57.1%. ConclusionEye evaluation by objective tests is a simple and reproducible method in patients with Sjögren's syndrome. The most affected indices were those of a decrease in tear production. The ocular stains did not have a direct relationship with the positivity of antibodies, nor rheumatoid factor.

LUPUS: Trends of the disease in Northwest Punjab

Objectives: The aim of this study was to study the clinical profile of systemic lupus erythematosus (SLE) patients from a tertiary care center in Northwest Punjab. Materials and Methods: It was an observational cross-sectional study conducted at the Rheumatology Clinic, Adesh Hospital, Bathinda. Twenty-five patients classified to be suffering from SLE as per standard classification criteria (Systemic Lupus International Collaborating Clinics [SLICC]) were enrolled after obtaining consent for the same. Socio-demographic data, disease duration, disease activity, and treatment received were recorded. Analysis was performed for the various parameters. Results: The majority of patients (88%) were females with a female to male ratio of 7.3:1 with mean age of 30.5 years. Mucocutaneous involvement (92%) followed by musculoskeletal (84%). Nephritis was seen in 36%, deforming arthritis in 8%, and pleural involvement in 36% while ILD in 12%. Pericarditis was seen in 16%, and myocarditis was seen in 12%. Neurological involvement was seen in 36% patients with two cases of thrombotic CVA, one case of SAH and three cases of seizure disorder. Psychiatric symptoms were observed in 16% cases. AIHA was seen in 12%, leukopenia in 44%, and thrombocytopenia in 68%. Most common antibody was anti-dsDNA being present in 48% cases, followed by Anti Ro-60, Ro-52, Anti Sm, and Anti U1RNP antibody. Conclusion: We found a striking difference in the prevalence of pleuropulmonary features, neuropsychiatric features, Leukopenia, and thrombocytopenia in our subgroup of population as compared to the earlier studies from central and southern parts of India thus further emphasizing the fact that ethnic backgrounds predispose a patient for different phenotype.

A study of antigen-specific anti-cytomegalovirus antibody reactivity in patients with systemic sclerosis and concomitant anti-Ro52 antibodies.

Anti-Ro52 autoantibody (autoAb), highly prevalent in Sjogren's syndrome (SjS) and systemic lupus erythematosus (SLE), is also frequent in systemic sclerosis (SSc). Viral agents, such as human cytomegalovirus (HCMV), have been considered as a trigger for SSc and SSc-associated autoAbs. To seek for antigen-specific anti-HCMV associations with anti-Ro52, we assessed the dominant anti-HCMV ab responses in anti-Ro52 antibody (ab)-positive and -negative patients with SSc and compared them with those in SLE and SjS. 116 Anti-HCMV ab(+) sera were analyzed, including 70 from anti-Ro52(+) patients (29 SSc, 23 SLE and 18 SjS) and 46 from anti-Ro52(-) patients (29 with SSc, 9 with SLE and 8 with SjS) as negative controls. Abs against specific HCMV pp130/UL57, pp65/UL83, pp55/UL55, pp52/UL44, p38 and pp28/UL99 antigens were tested by immunoblotting. Anti-Ro52(+) SSc patients reacted more frequently against pp52/UL44 and p38 compared to anti-Ro52(-) [(13/29, 44.8%; 95% CI 26.7-62.9% vs. 1/29, 3.4%; 95% CI 0-10%, p < 0.001, and 9/29, 31.0%; 95% CI 14.2-47.8% vs. 2/29, 6.9%; 95% CI 0-16.1%, p = 0.041, respectively]. No such differences were noted between anti-Ro52(+) and anti-Ro52(-) SLE or SjS patients. Also, antibody titres against HCMV pp65/UL83, pp52/UL44 and p38 antigens were higher in anti-Ro52(+) than anti-Ro52(-) SSc patients (p < 0.01). Ab responses against specific HCMV antigens differ among anti-Ro52 ab-positive and -negative patients with SSc (as well as between SSc and SLE or SjS), but whether these differences are epiphenomenal remains to be seen.

A Broader Perspective on Anti-Ro Antibodies and Their Fetal Consequences-A Case Report and Literature Review.

The presence of maternal Anti-Ro/Anti-La antibodies causes a passively acquired autoimmunity that may be associated with serious fetal complications. The classic example is the autoimmune-mediated congenital heart block (CHB) which is due in most cases to the transplacental passage of Anti-Ro/Anti-La antibodies. The exact mechanisms through which these pathologic events arise are linked to disturbances in calcium channels function, impairment of calcium homeostasis and ultimately apoptosis, inflammation and fibrosis. CHB still represents a challenging diagnosis and a source of debate regarding the best management. As the third-degree block is usually irreversible, the best strategy is risk awareness and prevention. Although CHB is a rare occurrence, it affects one in 20,000 live births, with a high overall mortality rate (up to 20%, with 70% of in utero deaths). There is also concern over the lifelong consequences, as most babies need a pacemaker. This review aims to offer, apart from the data needed for a better understanding of the issue at hand, a broader perspective of the specialists directly involved in managing this pathology: the rheumatologist, the maternal–fetal specialist and the cardiologist. To better illustrate the theoretical facts presented, we also include a representative clinical case.

Estimation of Some Immunological and Biochemical in the Patients with Systemic Lupus Erythematosus in Males and Females in Baghdad

Background: Systemic lupus erythematosus (SLE) is the prototypic multisystem autoimmune disease caused by the mistakenly in the body immune system that attacks healthy tissue in many parts of the body. Autoimmune thyroiditis (AT) is an organic-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. Methods: the study consist of 90 subjects from the both sexes were registered in this study.. The subjects have been divided in to three groups, group one and group two represent the patient groups that include, (30 SLE patients without taking steroid drugs group one (3male-27female) and 30 SLE patients with taking steroid drugs group two (2male-28female) with age range (16-57)years and thirty healthy subjects regards as a control (5male-25female)). Various clinical and laboratory parameters of SLE were measured for each groups. Also thyroid function tests were measured, which included free T3, free T4 and TSH. Antimicrosomal was measured for all groups were estimated by VIDAS method. Results: the results showed thyroid disorders were common (23.33%%) in lupus patients. Hypothyroidism was the commonest (13.33%) abnormality in SLE patients then hyperthyroidism (1.66%). At the same time, the results showed significance decreasing (p<0.01) in level of FT3 in (G1 and G2) when compared with the control group. Also, the results showed high significant decrease (p<0.01) in level of FT4 in (G2) comparison with both groups (G1) and control group. But, The results showed no significant differences (P<0.01) in level of TSH comparison with other studies groups included in the study. Further antiTPO a significant increasing (p<0.01) in (G1) comparison with both groups (G2) and control group. Then this study revealed a significance increasing of ESR, hsCRP, anti dsDNA, and ANA in both patients groups rather than control group.

Sjögren's Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and have a Germinal Center T Follicular Helper Transcriptional Profile.

To assess the types of salivary gland (SG) T cells contributing to Sjögren’s syndrome (SS), we evaluated SG T cell subtypes for association with disease features and compared the SG CD4+ memory T cell transcriptomes of subjects with either primary SS (pSS) or non-SS sicca (nSS). SG biopsies were evaluated for proportions and absolute numbers of CD4+ and CD8+ T cells. SG memory CD4+ T cells were evaluated for gene expression by microarray. Differentially-expressed genes were identified, and gene set enrichment and pathways analyses were performed. CD4+CD45RA− T cells were increased in pSS compared to nSS subjects (33.2% vs. 22.2%, p < 0.0001), while CD8+CD45RA− T cells were decreased (38.5% vs. 46.0%, p = 0.0014). SG fibrosis positively correlated with numbers of memory T cells. Proportions of SG CD4+CD45RA− T cells correlated with focus score (r = 0.43, p < 0.0001), corneal damage (r = 0.43, p < 0.0001), and serum Ro antibodies (r = 0.40, p < 0.0001). Differentially-expressed genes in CD4+CD45RA− cells indicated a T follicular helper (Tfh) profile, increased homing and increased cellular interactions. Predicted upstream drivers of the Tfh signature included TCR, TNF, TGF-β1, IL-4, and IL-21. In conclusion, the proportions and numbers of SG memory CD4+ T cells associate with key SS features, consistent with a central role in disease pathogenesis.

A comparative study on clinical characterizations between acute myelitis onset of neuromyelitis optica spectrum disease and idiopathic transverse myelitis

ABSTRACT Background/Aims Both of neuromyelitis optica spectrum disease (NMOSDs) and idiopathic transverse myelitis (ITM) could present as acute transverse myelitis. However, long-term immunological treatment and prognosis are different for high recurrence of NMOSDs. In this study, we summarized clinical differences between acute attack myelitis of NMOSDs and ITM, we further screened serum auto-antibodies to help understand the two distinct clinical entities. Methods This is a retrospective study on 48 NMOSD patients and 49 ITM patients in neurological department of Nanjing Drum Tower Hospital from 2013 to 2019. Clinical, CSF and MRI profiles on the acute episode were also compared between NMOSD patients and ITM patients. Serum AQP4 and auto-antibodies were tested. Clinical parameters were further compared between NMOSD patients with and without auto-antibodies. Results Compared with ITM patients, NMOSD patients manifested with longer vertebral segments (5.42 ± 3.17 segments vs. 2.31 ± 2.36 segments, p < 0.001), higher female/male ratio (13:3 vs. 20:29, p < 0.001), higher IgG index (30.30% vs. 9.09%, p < 0.05). Positive rates of anti-Ro-52 (47.92% vs. 14.29%, p < 0.001), anti-ANAs (50.00% vs.10.20%, p < 0.001) and anti-SSA (35.42% vs. 6.12%, p = 0.001) were significantly higher in the NMOSD patients than the ITM patients. Seropositive Ro-52 and SSA were associated with longer injured spinal cord segments. However, Ro-52 antibody may not be associated with NMOSD relapsing during our follow up. Conclusions NMOSD patients manifested with longer vertebral segments, higher female/male ratio, IgG index, anti-ANAs, anti-Ro-52 and anti-SSA seroprevalence than ITM patients. These features may help clinicians better distinguish NMOSD from ITM and provide long-term immunotherapy reasonably.

AB0555 ANTI-RO POSITIVITY EFFECT ON CLINICAL CHARACTERISTICS AND MORTALITY IN A SINGLE-CENTER COHORT OF ANTISYNTHETASE SYNDROME PATIENTS

Background:Antisynthetase syndrome (ASSD) is an heterogeneous disease characterized by the occurrence of anti-synthetase antibodies (ARS) and the classic triad of arthritis, myositis and Interstitial Lung Disease (ILD). Pulmonary involvment bears an increased risk of life threatening events, being the main cause of mortality in these patients. No significant differences in mortality have been noticed among the different ARS specificities. However the role of extractable nuclear antigen antibodies on mortality in these patients is still matter of debate.Objectives:To asses the effect of anti-RO antibodies on clinical characteristics and mortality in a large italian single-center cohort of ASSD patients.Methods:Cohort study of outcome, clinical and laboratory characteristics, at baseline and at last follow-up, of 55 ASSD patients progressively enrolled and followed-up at our out-patient clinic. Survival was estimated with Kaplan-Meier function and comparison between frequencies of clinical characteristics was studied with Chi-square test.Results:We identified 30 anti-Ro+ (M:F=1:4) and 25 anti-Ro- (M:F=1.5:1) ASSD patients. No difference in the age of onset was observed (p value=0.83). Classic triad prevalence and evolution was similar between the two groups with only significant difference of ILD prevalence at last follow up, higher in anti-Ro+ patients group (p value=0.01). Overall mortality was of 13 subjects (23%) during the follow-up period (median 53 months, IQR 16-114). Despite the significantly higher pulmonary involvment in the anti-Ro+ group no difference between mortality in anti-Ro positive and negative groups was observed. Adjusting mortality to include disease-related events only did not provide any additional difference (p value=0.5) (Table 1). Survival curves of the two groups were not different at any time point (Log-rank test, p value 0.98) (Figure 1).Table 1.Clinical and Demographic Characteristics of the cohortASSDRo+Ro-P valuePZ (M:F)30 (6:24)25 (14:10)/Age (years) at disease onset (median, IQR)56 (43-69)54 (46-68)0.83Disease duration (months) (median, IQR)55 (23-112)52 (13-130)0.681Arhtritis at onset (%)22 (73)17 (68)0.664Arhtritis at last follow-up (%)26 (86)18 (72)0.175Myositis at onset (%)12(40)15 (60)1Myositis at last follow-up (%)19 (63)21 (84)0.086ILD at onset (%)20 (66)12 (48)0.162ILD at last follow-up (%)30(100)20 (80)0.01Complete form at onset (%)8 (26)4 (16)0.34Complete form at last follow-up (%)17 (56)13 (52)0.729Raynaud phenomenon (%)7 (23)8 (32)0.472Mechanic’s hands (%)12 (40)12 (48)0.551Death (%)7 (25)6 (24)0.953Disease related death (%)3 (42)4 (66)0.506Figure 1.Kaplan-meier curve of anti-Ro+ and anti-Ro – ASSD patients.Conclusion:The clinical spectrum and the time course of ASSD is not significantly affected by the presence of anti-Ro antibodies, althuough ILD seems to be more associated to anti-Ro antibodies. Despite higher prevalence ofILD in Ro positive group no difference in mortality was observed in respect to anti-Ro negative patients.

AB0125 EXPRESSION OF INTERFERON TYPE I- AND TYPE II-INDUCED GENES IN PATIENTS WITH SJÖGREN’S SYNDROME WITH AND WITHOUT EXTRAGLANDULAR INVOLVEMENT

Background:It is well known that Sjögren’s syndrome (SjS) is characterized by an upregulation of interferon (IFN)-induced genes. Namely, IFN type I signature has been reported in peripheral blood mononuclear cells (PBMCs) and in salivary glands of patients with this disease. However, few data are available on possible variability of IFN-induced gene upregulation in different clinical phenotypes of SjS.Objectives:To verify whether upregulation of IFN-induced genes is comparable in patients with SjS characterized by different clinical phenotypes, i.e., patients with systemic extraglandular manifestations (EGMs) versus patients with a disease limited to glandular features (GFs) and with widespread pain (WP).Methods:The study population was composed by 11 patients with SjS and EGMs (1 male, age range 18-78 years), and 10 patients with only GFs and WP (all females, age range 46-81 years), all classified according to ACR-EULAR criteria. The prevalence of anti-SSA(Ro) antibodies was 11/11 and 8/10, respectively. Lip biopsy was positive in all cases. Six healthy normal subjects were also included in the study as control population.Four IFN type I- and 5 IFN type II-induced genes were chosen for the study on the basis of previous literature data. Total RNA from each patient and control was isolated from purified PBMCs, followed by cDNA preparation and real time quantitative-PCR (RQ-PCR) analysis, using specific primer/probe sets. For calculation of relative expression, all samples were normalised against expression of a household gene (beta actin). A further normalization was performed against the mean value of relative expression obtained in the normal controls. Final fold change values were determined from the double-normalised values using the 2−ΔΔCT method (Applied Biosystems).Results:Fold change values of gene expression of both IFN type I- and type II-induced genes in PBMCs were different in the two clinical phenotypes of SjS. Fold change values of IFN type I-induced genes appeared strongly higher in patients with EGM, and some of them only moderately increased in those with only GF and WP. The expression of some of IFN type II-induced genes were slightly increased in patients belonging to both clinical phenotypes. Results are detailed in the table.Table.Fold change values of gene expression in patients with SjS plus EGMs, in patients with disease limited to GF and WP, and in controls.GeneMX1IFIT1IFT3IFI44IDO1GRP1MIGIP-10P2RY14SjS-EGMs85.938.524.440.425.18.34.51.55.5SJS-GF-WP4.21.72.04.84.11.20.60.31.3Controls2.11.61.11.51.41.31.51.31.4Legend. IFN type I-induced genes: MIX, IFN-induced GTP binding protein 1; IFIT1, IFN-induced protein with tetratricopeptide repeats 1; IFIT3, IFN-induced protein with tetratricopeptide repeats 3; IFI44, IFN-induced protein 44.IFN type II-induced genes: IDO1, indolamine-deoxygenase 1; GBP1, guanylate binding protein 1; MIG, C-X-C chemokine 9 (CXCL9); IP-10, C-X-C chemokine 10 (CXCL10); P2RY14, purinergic receptor 14.Conclusion:The present data indicate that IFN type I- and, to a lesser degree, type II-induced genes are upregulated in patients with SjS, but this phenomenon is consistently stronger in patients with systemic EGMs. In patients with only GFs IFN-induced gene upregulation is milder in PBMCs, and then probably more restricted to the exocrine target tissues.Disclosure of Interests:Nicoletta Del Papa: None declared, Claudio Vitali: None declared, Maurizio Lorini: None declared, Vincenzo Carbonelli: None declared, Wanda Maglione: None declared, Francesca Pignataro: None declared, Antonina Minniti: None declared, Nicola Montano: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp &amp; Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

AB0624 PREDICTIVE PARAMETERS FOR DEVELOPMENT OF INTERSTITIAL LUNG DISEASE IN IDIOPATHIC INFLAMMATORY MYOSITIS

Background:Idiopathic Inflammatory Myositis (IIM) is a group of heterogeneous connective tissue diseases, primarily characterized by chronic muscle inflammation as well as myositis-specific or myositis-associated autoantibodies and a spectrum of different extra-muscular features.The most frequent organ involment in IIM is Interstitial Lung Disease (ILD), occurring in 5-80% of different IIMs cases and considered the hallmark of morbidity and mortality in patients with IIMs.Objectives:To retrospectively assess the predictive factors for development of ILD in IIM patientsMethods:We retrospectively analyzed the prevalence of ILD in a single-center cohort of 165 IIM patients. Patient data was collected from clinical charts. ILD was diagnosed by chest X-ray scan and chest CT scan. All chest CT and chest X-ray scans available and performed at our hospital were consequently re-evaluated by our expert pneumologist for uniform evaluation.Results:Myositis-related ILD (M-ILD) was found in 52 IIM patients (31.5%): 46.15% was affected by anti-synthetase syndrome (ARS), 21.15% by polymyositis (PM), 19.23% by dermatomyositis (DM) and 13.46% by overlap myositis. The pulmonary involvement was characterized by Non-specific interstitial pneumonia (NSIP) (30.6%), Unusual Interstitial Pneumonia (UIP) (38.77%), Bronchiolitis Obliterans with Organizing Pneumonia (BOOP) (20.4%), overlap NSIP/BOOP (4.1%) and Undetermined/Unspecific pattern (6.12%). Eighty four percent of M-ILD consisted of non-smokers and 69.23% presented with dyspnea at onset.ILD was diagnosed in 90.38% of patients within the first year of IIM diagnosis (early onset ILD) and was associated with dyspnea and/or cough in 70.2% and 17% respectively. On the other hand, late onset ILD presented mostly with dyspnea and/or cough in 60% of cases and was significantly associated with anti-Ku antobodies.At onset ILD was significantly associated with: ARS (p&lt;0.0001; OR:12.98), anti-Jo-1 (p&lt;0.0001; OR:6.1), anti-Ro (p=0.038; OR:2.2), mechanic’s hands (p&lt;0.0001; OR:10.41), arthritis (p=0.01; OR:2.58), polyarthritis (p=0.001; OR:4.578), dyspnea (p&lt;0.0001; OR:9.66), and high levels of CPK (p=0.0001) and GOT (p=0.0146). By contrast, the following features: DM (p=0.012; OR:0.36), facial rash (p=0.003; OR:0.31), anti-NXP-2 (p=0.019; OR&lt;0.0001), anti-PL-12 (p=0,03; OR&lt;0.0001) and myositis (p&lt;0.0001; OR:0.173) present at onset were less frequently associated with M-ILD.At multivariate analysis M-ILD was predicted by anti-Ro (p=0.0448), polyarthritis (p=0.0093) and dyspnea (p=0.0001) at onset. On the other hand, patients presenting myositis (p=0.0383) and facial rash (p=0.0398) at onset were less likely to developed M-ILD.Conclusion:ILD occurs in about one third of patients with IIM, mostly affected by ARS. The presence of anti-Ro antibodies as well as polyarthritis and dyspnea at onset predict the development of ILD.Disclosure of Interests:None declared

Novel shared antibody specificities in anti-Ro/ La antibody negative Sjögren’s Syndrome

Abstract INTRODUCTION Sjögren’s syndrome (SS) is a rheumatic autoimmune disease characterized by focal lymphocytic infiltrates in the lacrimal and salivary glands, severe dry mouth and eyes, pain and debilitation. Diagnosis requires autoantibodies to ubiquitous Ro antigens or a lip biopsy positive for focal lymphocytic infiltrates. Here we used human proteome arrays to identify novel antibodies in plasma from Ro positive and Ro/La antibody negative SS patients compared with healthy controls. METHODS Anti-Ro positive (n=15) and anti-Ro negative (n=15) cases meeting 2016 ACR/EULAR classification criteria for SS were age, race, and sex matched with each other and healthy controls (n=15). Plasma IgG binding to human proteome arrays containing &amp;gt;19,500 recombinant human proteins representing &amp;gt;80% of the human proteome (HuProt v3.2 arrays, CDI Laboratories) was assessed. Data were normalized by the Robust Linear Model using the PAA Bioconductor Package in R and log intensity values for each protein generated. Thresholds of mean + 4SD were established using the controls. Antigens bound by IgG more frequently in cases compared to controls (p&amp;lt;0.05, one-tailed Fisher’s exact test) were considered significant. RESULTS IgG from Ro positive SS cases significantly bound 18 proteins, including the canonical SS antigens Ro60 and Ro52. IgG from Ro negative SS cases significantly bound 4 proteins compared to controls, 3 of which were shared with the Ro positive group. Binding to any one of 4 novel proteins identified 73% of the Ro negative SS cases. CONCLUSION A total of 17 novel antigen specificities were identified in SS, with 4 antigens being bound by plasma IgG from Ro/La negative SS cases. These antigens may be useful for diagnosing SS without a lip biopsy.

Sjögren’s syndrome minor salivary gland CD4+ T cells associate with glandular disease features and have a germinal center T follicular helper transcriptional profile

Abstract Objective To assess the types of salivary gland (SG) T cells contributing to Sjögren’s syndrome (SS), we evaluated SG T cell subtypes for association with disease features and compared the SG CD4+ memory T cell transcriptomes of primary SS (pSS) and sicca subjects not meeting SS criteria (nSS). Methods SG biopsies of pSS and nSS subjects were evaluated for proportions (n=51 pSS, n=69 nSS) and absolute numbers (n=35 pSS, n=57 nSS) of CD4+ and CD8+ T cells. SG memory CD4+ T cells from focus score positive pSS (n=17) and focus score negative nSS subjects (n=15) were evaluated for gene expression by microarray. Differentially-expressed genes were identified and gene set enrichment and pathways analyses were performed. Results CD4+CD45RA− T cell frequencies were increased in pSS compared to nSS subjects (33.2 vs. 22.2%, p&amp;lt;0.0001), while CD8+CD45RA− T cells were decreased (38.5 vs. 46.0%, p=0.0014). SG fibrosis positively correlated with numbers of memory T cells, regardless of phenotype. Proportions of SG CD4+CD45RA− T cells correlated with focus score (r=0.43, p&amp;lt;0.0001), corneal damage (r=0.43, p&amp;lt;0.0001), and serum Ro antibodies (r=0.40, p&amp;lt;0.0001). Differentially expressed genes in CD4+CD45RA− cells of pSS versus nSS subjects indicated a T follicular helper (Tfh) profile, increased homing and increased cellular interactions. Predicted upstream drivers of the Tfh signature included TCR, TNF, TGF-β1, IL-4 and IL-21. Conclusions The proportions and numbers of SG memory CD4+ T cells associate with key SS features, consistent with a central role in disease pathogenesis. SG memory CD4+ T cells express a germinal center Tfh profile.