Undifferentiated Connective Tissue Disease Research Articles

Matrix metalloproteinases system profile analysis and their endogenous inhibitors in children with periodontal diseases and various dysplasia phenotypes

Relevance. The search and development of modern non-invasive methods for early periodontal disease detection are of scientific and practical value for a personalized approach to disease course prognosis and explaining the choice of treatment tactics. Morphological immaturity, high intensity of anabolic processes, functional failure of neurohumoral, endocrine and immunological defence systems combined with an imbalance between the synthesis and degradation of extracellular matrix components in children with undifferentiated connective tissue disease (UCTD) significantly increases the risk of developing periodontal diseases. The available data on the activity of salivary matrix metalloproteinases (MMPs), which play a leading role in regulating connective tissue protein metabolism and bone remodelling mechanisms in children with UCTD of various degrees, are scarce and require further study.Purpose. The study aimed to explain the clinical, diagnostic and prognostic value of MMPs as markers of inflammatory periodontal diseases in children with UC TD and dysplastic disorders of various se verity.Material and methods. The study included 67 children with UCTD (main group) and 34 children of health groups I and II (comparison group) aged 12-17. The UCTD severity was established according to the diagnostic criteria by L. N. Abbakumova (2006) and a scale for assessing the significance of phenotypic and visceral signs. The main group was divided into two subgroups: Subgroup 1 (n = 38) – children with mild and moderate UCTD; Subgroup 2 (n=29) – children with severe UCTD. The studied groups had their periodontal status assessed, as well as the concentration of MMP-1, MMP-2, MMP-8, MMP-9 and their tissue inhibitors (TIMP-1, TIMP-2) in the oral fluid identified using the enzyme immunoassay, along with calculation done for the MMP ⁄ TIMP coefficients that set a balance between the degradation and synthesis of collagen.Results. The children with phenotypic signs of UCTD in the oral fluid appeared to show a statistically significant increase in the MMP-1, MMP-2, MMP-8, and MMP-9 levels and an imbalanced ratio in MMP-1⁄TIMP-1, MMP- 2⁄TIMP-2, MMP-8⁄TIMP-1, MMP-9⁄TIMP-1, compared with health groups I, II. An increase in the MMP-1, MMP-2, and MMP-8 concentrations, along with dominating expression of MMP-9 over TIMP-1 in the oral fluid of children of Subgroup 2, causes an increase in intensity and prevalence of periodontal diseases compared to the patients in Sub-group 1 and comparison group.Conclusion. Thus, when children with UCTD don’t demonstrate an increase in specific tissue inhibitors TIMP-1 and TIMP-2 in their oral fluid, along with an increase in the levels of the respective matrixins is the key pathogenetic factor in the degradation of extracellular matrix proteins, which causes a depressing impact on the proliferative activity in the periodontal set of tissues.

Capillaroscopic findings in undifferentiated connective tissue disease with Raynaud’s phenomenon

Background: Undifferentiated connective tissue disease (UCTD) is characterized with presence of clinical signs and immunological findings suggestive of connective autoimmune disease, but the criteria for a definite rheumatic disease are not fulfilled. Raynaud’s phenomenon (RP) could be found in approximately 50% of cases with UCTD and about half of patients with UCTD and RP exhibit “scleroderma-like” pattern.
 The aim of the study: To assess the characteristics of capillaroscopic changes in early UCTD.
 Patients and methods: Inclusion criterion for the study was newly diagnosed by rheumatologist, early UCTD in patients with RP. 26 patients were included in the study – 24 females and 2 males, mean age 38±14 years (range 19 – 66 years). Capillaroscopic examination was performed in all patients using USB microscope Dino-Lite. Follow-up was perfomed for a period between 1 and 3.5 years.
 Results and discussion: At the time of the initial diagnosis, “scleroderma-like” pattern, “early” phase (giant capillaries, presence of hemorrhages in some cases, preserved distribution, normal capillary density) was found in 17 patients (65%). More advanced capillaroscopic changes including devascularization and derangement were not observed. In 4 patients nonspecific capillaroscopic findings were present (dilated capillaries, hemorrhages, increased tortuousity, elongated capillaries,) and in 5 cases – normal capillaroscopic picture was found. During the follow-up in one patient the diagnosis was revised to systemic lupus erythematous due to newly appeared clinical, laboratory and immunological findings. The normal capillaroscopic pattern was changed to nonspecific findings in this case. Two patients fulfilled the criteria for prescleroderma during the follow-up without skin and visceral involvement. In the rest patients clinical diagnosis and capillaroscopic findings remained unchanged.
 Conclusion: In conclusion, “scleroderma” type microangiopathy, “early” phase is a common finding in UCTD with RP, while more advanced microvascular pathology is not usually observed. Stable capillaroscopic pattern during the follow-up correlates with the stable clinical course. Capillaroscopy is a key technique for assessment of RP patients in rheumatology and for early diagnosis of UCTD with peripheral vascular syndrome.

Analysis of adverse neonatal outcomes in pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies

Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.

Anti-SSA Ro52 and anti-Ro60 autoantibodies: association with clinical phenotypes.

Anti-SSA autoantibodies can be differentiated according to their antigenic target proteins as anti-Ro60 (60 kDa) or anti-Ro52 (52 kDa). Anti-SSA(Ro60) antibodies are clearly associated with connective tissue diseases (CTD), but the clinical significance of anti-SSA(Ro52) antibodies remains unclear. The aim of the present study was to analyse the disease phenotype of patients with anti-Ro52 and/or anti-Ro60 antibodies. A multicentre, cross-sectional study was carried out of positive anti-Ro52 and/or Ro60 antibodies patients followed at 10 Rheumatology centres from January 2018 until December 2021. Patients were categorised into 3 groups: group 1 (Ro52+/Ro60-); group 2 (Ro52-/Ro60+); group 3 (Ro52+/Ro60+). Antinuclear antibodies were evaluated by indirect immunofluorescence assay and further screened for anti-extractable nuclear antigen (ENA) antibodies. Demographicsand clinical data were compared between the 3 groups, by patients' medical chart review. Univariate analysis was performed and subsequently logistic regression was used to identify intergroup differences and calculate the odds ratio with a 95% confidence interval (95% CI). We included 776 patients [female: 83.1%; median age: 59 (46-71) years]. Groups 1, 2, and 3 comprised 31.1%, 32.6%, and 36.3% of the patients, respectively. Anti-Ro52 antibody alone was more frequently associated with non-rheumatic diseases, older age, and men (p<0.05). Among patients with CTD, the diagnosis of systemic lupus erythematosus is 3 and 2 times more prevalent in groups 2 and 3, respectively, than in group 1 [OR 2.8 (95% CI 1.60, 4.97), p<0.001; OR 2.2 (95% CI 1.28, 3.86), p<0.01]. In group 2, the diagnosis of undifferentiated CTD is more frequent than in the other groups. Group 1 was more frequently associated with inflammatory myositis than group 2 [OR 0.09 (95% CI 0.01, 0.33), p<0.001] or group 3 [OR 0.08 (95% CI 0.01, 0.29), p<0.001]. Group 1 was also more frequently associated with arthritis (p<0.01), interstitial lung disease (p<0.01), and myositis (p<0.01). Anti-Ro52+ antibody alone is frequently found in patients with non-rheumatic diseases. In addition, anti-Ro52+ antibody is also prevalent in patients with CTD and associated with clinical phenotypes that are different from anti-Ro60+ antibody.

Connective tissue disease related interstitial lung disease: a single center experience

Objectives: We aimed to determine the clinical features of the patients followed by our hospital with the diagnosis of connective tissue disease related interstitial lung disease (CTD-ILD). Methods: The study included 113 patients who were followed up with the diagnosis of CTD-ILD, admitted to Kahramanmaraş Sütçü İmam University, Faculty of Medicine, Rheumatology Department between January 2019 and December 2020. Demographic characteristics, laboratory data and high-resolution computed tomography (HRCT) patterns of the patients were recorded retrospectively. Results: Of 113 patients diagnosed with CTD-ILD; 90 were female, 23 were male. When the distribution of connective tissue disease (CTD) evaluated; 50 were rheumatoid arthritis, 41 were systemic sclerosis, 8 were sjogren's syndrome, 4 were systemic lupus erythematosus, 7 were overlap syndrome and 3 were undifferentiated connective tissue disease. There was no statistically significant difference between laboratory parameters. In the HRCT evaluation, 86 patients had nonspecific interstitial pneumonia (NSIP), 25 patients had usual interstitial pneumonia (UIP), and 2 patients had lymphocytic interstitial pneumonia (LIP) pattern. The most common pattern, including rheumatoid arthritis, was NSIP. Conclusions: In our study, as inconsistent with the literature the most common pattern in RA patients was found to be NSIP.

Assessment of N-terminal pro-brain natriuretic peptide in patients with arrhythmia due to undifferentiated connective tissue disease

Aim. To study the relationship between the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and myocardial abnormalities in patients with cardiac arrhythmias due to undifferentiated connective tissue disease (UCTD).Material and methods. This cross-sectional comparative study included young and middle-aged patients with arrhythmias due to UCTD: group 1 (18-44 years old, n=127), group 3 (45-59 years old, n=10). The control groups (n=30, group 2; n=8, group 4) included volunteers with single phenotypic signs of UCTD, comparable in age and sex. A standard clinical examination, 72-hour electrocardiographic monitoring, Speckletracking echocardiography, and NT-proBNP level assessment were performed.Results. In patients of groups 1 and 3, a significant increase in the concentration of NT-proBNP was noted compared to the control groups. At the same time, the average NT-proBNP level in the study groups did not exceed the reference values. Significant correlations were revealed between NT-proBNP and heart rate (r1=0,462, p=0,010; r3=0,397, p=0,034), UCTD diagnostic cut-off level (r1=0,496, p=0,001; r3=0,401, p=0,043), the presence of mitral valve prolapse (r1=0,469, p=0,002) and mitral regurgitation (r1=0,53, p=0,008), premature ventricular contractions (PVCs) of class III (r1=0,582, p=0,045), IVa (r1= 0,39, p=0,042) and V (r1=0,397, p=0,037); cardiac index (r1=-0,329, p=0,037) and ejection fraction (r1=-0,407, p=0,044). However, no significant correlation was found between the left ventricular global longitudinal strain and NT-proBNP level.Conclusion. The study demonstrated the association of NT-proBNP level with UCTD diagnostic cut-off level, mitral valve prolapse, mitral regurgitation, and PVCs, which makes possible the use of this biomarker as an additional diagnostic criterion for myocardial changes in against the background of UCTD.

P18 Bullous leukocytoclastic vasculitis in a patient with known undifferentiated autoimmune rheumatic disease

P18 Bullous leukocytoclastic vasculitis in a patient with known undifferentiated autoimmune rheumatic disease

Undifferentiated connective tissue disease with an incidental photo-provocation: a case report

A female patient with undifferentiated connective tissue disease and no documented history of photosensitivity fastidiously adhered to the rheumatologist's recommendation to avoid UV light exposure. Due to unexpected UV exposure, she developed multiple erythematous/violaceous macules, concerning a cutaneous lupus erythematosus reaction with a chilblain-like appearance. This study highlighted the importance of screening for unintentional photo-provocation in those who are suspected of having or being at risk for developing systemic lupus erythematosus.

Systemic Lupus Erythematosus Risk Probability Index: ready for routine use? Results from a Chinese cohort

ObjectivesTo evaluate the performance of Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in patients with SLE using a Chinese cohort.MethodsThe Chinese cohort included 352 patients with and 385 without SLE...

Autoantibody status according to multiparametric assay accurately estimates connective tissue disease classification and identifies clinically relevant disease clusters

ObjectiveAssessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential...

Posterior reversible encephalopathy syndrome as the first presentation of a connective tissue disorder: A case report

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical-radiological diagnosis. Although hypertension is the main cause of this condition several secondary causes have been identified. Here we discuss a 53-year-old woman with a history of hypertension who presented with sudden onset of headache, seizures, and bilateral cortical blindness. MRI was suggestive of PRES. She had minimal blood pressure fluctuations. Antinuclear antibodies were significantly positive and a history of symmetrical polyarthritis was revealed. As the criteria for a particular connective tissue disorder were not fulfilled, the diagnosis of an undifferentiated connective tissue disease was made. In the presence of classical symptoms and imaging, PRES should be suspected even amongst patients without blood pressure fluctuations. Secondary causes should be identified and corrected in such patients.

Clinical Features and Outcome Analysis of Type B Insulin Resistance Syndrome: A Single-Center Study in China.

Type B insulin resistance syndrome (TBIRS) is a rare condition, for which effective treatment remains challenging. This work aimed to summarize the clinical characteristics of TBIRS and explore effective therapeutic strategies. The clinical manifestations, biochemical indices, and treatment of 8 patients (3 men and 5 women) with TBIRS from Peking Union Medical College Hospital were retrospectively analyzed and their clinical outcomes were evaluated. The average age of the patients was 49.5 ± 16.5 years, and the duration of the disease ranged from 2 months to 1 year. Seven patients with hyperglycemia had normal/lower triglycerides (TGs) and lower insulin-like growth factor 1 (IGF-1) levels. One patient complained of intractable hypoglycemia. Five patients had accompanied systemic lupus erythematosus, 2 had mixed connective tissue disease, and 1 had undifferentiated connective tissue disease. Five patients had acanthosis nigricans and 3 women of child-bearing age had hyperandrogenism. All 8 patients were treated with glucocorticoids combined with immunosuppressants, among whom, 5 received high-dose glucocorticoid pulse therapy followed by conventional-dose glucocorticoid therapy, all of whom achieved partial remission within 2 to 4 weeks. Among the 3 patients receiving conventional glucocorticoid therapy, 2 achieved partial remission within 2 to 4 weeks. Six patients were tracked for 10 weeks to 4 years; 4 and 2 achieved complete and partial remission, respectively. Decreased serum complement 3 and IGF-1 levels and normal/decreased TG levels act as striking biochemical features of TBIRS. High-dose glucocorticoid pulse therapy followed by conventional-dose long-term therapy combined with immunosuppressants achieves good clinical efficacy.

Distribution and clinical significance of anti-carbamylation protein antibodies in rheumatological diseases among the Chinese Han population.

Several studies have demonstrated that anti-carbamylation protein antibodies (Anti-CarPA) are persistent in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSC), primary Sjögren's syndrome (pSS), and interstitial lung disease associated with RA (RA-ILD). However, the relationship between anti-CarPA and other rheumatic diseases (RDs) and non-RA-ILD is not known till now. This study sought to examine the presence of anti-CarPA in Chinese Han patients with RDs and its clinical significance. The study included 90 healthy controls (HCs) and 300 patients with RDs, including RA, SLE, polymyositis/dermatomyositis (PM/DM), pSS, SSC, spondyloarthritis (SpA), anti-neutrophil cytoplasmic autoantibodies associated with vasculitis (AAV), undifferentiated connective tissue disease (UCTD), and Behcet's disease (BD). Antibodies against carbamylated human serum albumin were detected using commercial enzyme-linked immunosorbent assay kits. Correlations between clinical and laboratory parameters were analyzed. Serum levels of anti-CarPA in RA (34.43 ± 33.34 ng/ml), SLE (21.12 ± 22.23 ng/ml), pSS (16.32 ± 13.54 ng/ml), PM/DM (30.85 ± 17.34 ng/ml), SSC (23.53 ± 10.70 ng/ml), and UCTD (28.35 ± 21.91 ng/ml) were higher than those of anti-CarPA in the HCs (7.30 ± 5.05 ng/ml). The concentration of serum anti-CarPA was higher in patients with rheumatic disease-related interstitial lung disease (RD-ILD), especially RA-ILD, PM/DM-ILD, and pSS-ILD. Patients with RD-ILD who tested positive for anti-CarPA were more likely to have a more severe radiographic classification (grades II, p = 0.045; grades III, p = 0.003). Binary logistic regression analysis suggested that anti-CarPA had an association with ILD in RA (p = 0.033), PM/DM (p = 0.039), and pSS (p = 0.048). Based on receiver operating characteristics (ROC) analysis, anti-CarPA cutoffs best discriminated ILD in RA (>32.59 ng/ml, p = 0.050), PM/DM (>23.46 ng/ml, p = 0.038), and pSS (>37.08 ng/ml, p = 0.040). Moreover, serum levels of anti-CarPA were correlated with antibodies against transcription intermediary factor 1 complex (anti-TIF1) (R = -0.28, p = 0.044), antibodies against glycyl-transfer ribonucleic acid synthetase (anti-EJ) (R = 0.30, p = 0.031), and antibodies against melanoma differentiation-associated gene 5 (anti-MDA5) (R = 0.35, p = 0.011). Serum anti-CarPA could be detected in patients with RA, PM/DM, pSS, SSC, and UCTD among the Chinese Han population. And it may also assist in identifying ILD in patients with RA, PM/DM, and pSS, which emphasized attention to the lung involvement in anti-CarPA-positive patients.

Microvascular damage in autoimmune connective tissue diseases: a capillaroscopic analysis from 20 years of experience in a EULAR training and research referral centre for imaging

ObjectiveNailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of...

Epipericardial fat necrosis in chest CT and MRI: a case report of an unusual cause of chest pain associated with the initial diagnosis of undifferentiated connective tissue disease

BackgroundEpipericardial fat necrosis (EFN) is a benign and self-limited condition of unknown cause with a good prognosis, usually affecting otherwise healthy patients. Clinically, it presents with severe acute left pleuritic chest pain, often leading the patient to the Emergency Room (ER).Case presentationA 23-year-old male, smoker (5 pack-years), was evaluated in the ER due to left pleuritic chest pain, worsening with deep breathing and Valsalva maneuver. It was not associated with trauma and did not present other symptoms.The physical examination was unremarkable. The arterial blood gases while breathing room air and the laboratory tests, including D-dimers and high-sensitivity cardiac Troponin T, were normal. The chest radiograph, electrocardiogram, and transthoracic echocardiogram showed no abnormalities.A computed tomography (CT) pulmonary angiogram showed no signs of pulmonary embolism but depicted at the left cardiophrenic angle a focal 3 cm ovoid-shaped fat lesion with stranding and thin soft tissue margins, consistent with necrosis of the epicardial fat, which was confirmed by magnetic resonance (MRI) of the chest.The patient was medicated with ibuprofen and pantoprazole, with clinical improvement in four weeks. At a two-month follow-up, he was asymptomatic and presented radiologic resolution of the inflammatory changes of the epicardial fat of the left cardiophrenic angle on chest CT. Laboratory tests revealed positive antinuclear antibodies, positive anti-RNP antibody, and positive lupus anticoagulant. The patient complained of biphasic Raynaud’s phenomenon initiated five years ago, and a diagnosis of undifferentiated connective tissue disease (UCTD) was made.ConclusionsThis case report highlights the diagnosis of EFN as a rare and frequently unknown clinical condition, which should be considered in the differential diagnosis of acute chest pain. It can mimic emergent conditions such as pulmonary embolism, acute coronary syndrome, or acute pericarditis. The diagnosis is confirmed by CT of the thorax or MRI. The treatment is supportive and usually includes non-steroidal anti-inflammatory drugs. The association of EFN with UCTD has not been previously described in the medical literature.

Regulation of MicroRNA Expression in Scleroderma and Idiopathic Pulmonary Fibrosis: A Research Study

Introduction: Scleroderma (SSc) is an autoimmune disorder with the hallmark of fibrosis of the skin, vasculature and internal organs. Patients with SSc and undifferentiated connective tissue disease (UCTD) are susceptible to interstitial lung disease (ILD), leading to decreased lung function and death. Idiopathic pulmonary fibrosis (IPF) is a form of ILD that is not associated with extrapulmonary manifestations. In this study, lung involvement of SSc was studied by observing how disease progression and pathogenesis differ among patients with SSc, UCTD, and ILD compared to healthy controls and patients with IPF. Our group has previously identified disease targets through microRNA sequencing, including the DICER enzyme, which works closely with the protein DGCR8 and the enzyme DROSHA in the RNA interference pathway. The canonical pathway stipulates that DICER processes microRNAs in the cytosol while DGCR8 and DROSHA process microRNAs in the nucleus. DICER, DROSHA, and DGCR8 are hypothesized to contribute to ILD progression. Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from voluntary participants, including healthy controls. PBMCs were subsequently lysed with subcellular fractionation buffer. Western blotting was done on the resulting cytosolic and nucleic fractions for DICER, DROSHA, and DGCR8 protein expression. The cytosolic fractions were normalized to GAPDH, while the nucleic fractions were normalized to B2M. Nonparametric Kruskal‐Wallis tests were used for statistical analysis. Results: The medians were significantly higher for healthy controls for DICER in the nucleus with a p-value of 0.0302, and DROSHA in the cytosol with a p-value of 0.0406 compared to patients with SSc, UCTD, and IPF. Discussion: Differences in expression were found for DROSHA in the cytosol and DICER in the nucleus, suggesting dysregulation of the non-canonical RNA interference pathways in SSc, UCTD, and IPF patients. Variability of disease progression within the groups could lead to variable enzyme and protein levels within the same disease status. With larger sample sizes, statistically insignificant differences would become significant. Lipid nanoparticle technology could be used to deliver deficient microRNAs to silence mRNA in patients. Conclusion: Due to dysregulation of the RNA interference pathway, microRNAs may be inadequately processed in the patient groups.

AB1539 PREVALENCE OF ANTI-CN1A ANTIBODIES AND ITS CLINICAL SIGNIFICANCE – A RETROSPECTIVE MONOCENTRIC STUDY

BackgroundAnti-cytosolic 5’-nucleotidase 1A (anti-cN1A) antibodies have recently been proposed as a biomarker for inclusion body myositis (IBM). With high specificity (87-100%), they can help differentiate IBM from other myositis.[1,2]Besides IBM, it has been detected in other inflammatory conditions. Recently, a higher prevalence of IBM has been associated with Sjogren Syndrome (SS), and anti-cN1A has been associated with myositis in SS, regardless of the subtype of myositis.[3]However, it can also be detected in healthy individuals and despite its high specificity in IBM, it may not be a useful biomarker for the diagnosis of autoimmune conditions.[4]Thus, the clinical relevance of anti-cN1A remains unknown.ObjectivesThe aim of this study was to identify the clinical and laboratory manifestations associated with the presence of anti-cN1A.MethodsA retrospective study of patients with anti-cN1A positivity (detected by immunoblot assay), observed from January 2021 to December 2022, in a tertiary hospital, was conducted. Demographic, clinical and immunological data were collected. A descriptive analysis was made.ResultsSixty-five patients were positive for anti-cN1A: 53 women (81.5%) and the median age was 47.2±14.9 years. Rheumatic inflammatory diseases were diagnosed in 15 (22.7%) patients, of which 5 had systemic lupus erythematosus (SLE), 4 had SS, and 1 with rheumatoid arthritis, polymyalgia rheumatica, granulomatosis with polyangiitis, juvenile idiopathic arthritis, spondyloarthritis and undifferentiated connective tissue disease. Eight (12.1%) patients had autoimmune thyroiditis, without known rheumatic diseases associated. The presence of anti-cN1A was also found in the context of infection in 7 (10.6%) patients and malignancy in 2 (3.0%) patients. Half of the patients (50.8%) patients were healthy individuals. No diagnosis of IBM or other myositis was made. Twenty-nine (44.6%) patients showed other antibodies specificities: anti-SSA/Ro52 (20%), anti-Ku (4.6%), anti-Mi-beta2 (4.6%) and anti-DSF70 (4.6%). In the SLE and SS groups, the most frequent presenting clinical features were sicca syndrome (66.7%), lymphopenia (9.2%), arthritis (6.1%) and photosensitivity (3.1%). No patient had signs or symptoms of muscular involvement.ConclusionAnti-cN1A was detected in diverse rheumatic conditions, but also in autoimmune thyroiditis and mostly in healthy individuals. SLE and SS were the most frequent systemic autoimmune rheumatic diseases associated with these antibodies. Contrary to expectations, no diagnosis of IBM or myositis was made. Further studies regarding the clinical significance of anti-cN1A are needed to attribute the real diagnostic value of this marker.

Clinical Presentation of Connective Tissue Disease Patients with and without Interstitial Lung Disease: A Retrospective Study

Background: Connective tissue diseases (CTDs) are responsible for about 20% of interstitial lung disease (ILD) cases, but their diagnosis in a pulmonary unit (PU) is not always straightforward due to a heterogeneous clinical picture. Objectives: The aim of this study was to evaluate the clinical presentation of rheumatoid arthritis (RA) and CTD-ILD cases diagnosed in PU, compared to RA and CTD patients diagnosed in a rheumatologic unit (RU). Methods: Patients with RA, systemic sclerosis (SSc), primary Sjӧgren’s syndrome (pSS), and idiopathic inflammatory myopathy were retrospectively enrolled from an RU and a PU designated to manage ILD during a period from January 2017 to October 2022. The classification of CTD-PU was carried out in a multidisciplinary setting, including the same rheumatologists that diagnosed CTD in the RU. Results: ILD-CTD-PU patients were prevalently male and older. Progression from undifferentiated CTD to a specific condition was more common in ILD-CTD-PU, and those patients generally obtained a lower score on specific classification criteria. RA-PU patients resembled polymyalgia rheumatica in 47.6% of cases, also showing a greater proportion of typical joint deformities (p = 0.02). SSc-PU patients showed a usual interstitial pneumonia pattern in 76% of cases and, compared with SSc-RU, were more commonly seronegative (p = 0.03) and generally lacked fingertip lesions (p = 0.02). The majority of the diagnoses of pSS-PU were in patients with previously diagnosed ILD, in which seropositivity and sicca syndrome developed during follow-up. Conclusions: CTD-ILD patients diagnosed in the PU show severe lung involvement and a nuanced autoimmune clinical picture.

Anti-ganglioside antibody positive neuromyelitis optica spectrum disorders with peripheral neuropathy: a case report

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) is a group of autoimmune-mediated disorders of the central nervous system primarily involving the optic nerve and spinal cord. There are limited reports of NMOSD associated with peripheral nerve damage.Case presentationWe report a 57-year-old female patient who met the diagnostic criteria for aquaporin 4 (AQP4)-IgG positive NMOSD with undifferentiated connective tissue disease and multiple peripheral neuropathy. In addition, the patient was positive for multiple anti-ganglioside antibodies (anti-GD1a IgG antibodies and anti-GD3 IgM antibodies) and anti-sulfatide IgG antibodies in serum and cerebrospinal fluid. After treatment with methylprednisolone, gamma globulin, plasma exchange, and rituximab, the patient’s status improved and was subsequently discharged from our hospital.ConclusionsThe neurologist should be aware of the unusual association between NMOSD and immune-mediated peripheral neuropathy undifferentiated connective tissue disease and nerve damage mediated by multiple antibodies may have combined to cause peripheral nerve damage in this patient.

P037 The NIHR IMID Bioresource: a descriptive analysis of the first 5000 participants

Abstract Background/Aims The NIHR Immune-mediated inflammatory diseases (IMID)-Bioresource is a recallable resource of patients with an IMID, pre-disease states and unaffected first-degree relatives. Here, we report on the recruited cohort to date, focusing on co-existent comorbidities. Methods Patients are categorised into one of three primary IMID groups: rheumatoid arthritis (RA), axial-spondyloarthropathy-psoriasis spectrum (AxSpA-PsO: AxSpA, PsO, psoriatic arthritis [PsA], reactive arthritis) and systemic autoimmune rheumatic diseases (SARDs: systemic lupus erythematosus [SLE], mixed and undifferentiated connective tissue disease). Data were collected on clinical phenotype, secondary IMIDs, medications and key co-morbidities. Results 5028 participants (4965 IMIDs, 46 pre-disease, 17 relatives) have been enrolled to the IMID-Bioresource Sept-2020-Aug-2022 from 63 UK-centres. Of those with a diagnosed IMID, RA (N = 2472) was the largest group, then AxSpA-PsO (N = 2012) and SARDs (n = 479). Two-thirds (N = 3210, 64.7%) female, median (IQR) age 57.9 (47.3-67.6) years. 1544 (62.5%) patients with primary IMID RA were seropositive. The commonest AxSpA-PsO diseases included PsO (N = 1232, 24.8%), PsA (N = 1116, 22.5%) and AxSpA (N = 467, 9.4%). SLE was the commonest SARD (N = 376, 7.6%), a third (N = 133, 35.4%) reported previous lupus nephritis. 1241 (25.0%) patients reported &amp;gt;1 IMID diagnoses. The commonest overlaps were PsO and RA (N = 108, 2.2%), PsO and AxSpA (N = 72, 1.5%) and RA and Sjögren’s syndrome (N = 65, 1.3%). 2880 (58.0%) reported minimum one (range 1-11) co-morbidity, the commonest, hypertension (N = 1201, 24.2%), depression (N = 820, 16.5%) and asthma (N = 580, 11.7%). 274 (5.5%) patients reported ischaemic heart disease, commonest in RA (N = 152, 6.2%). Interstitial lung disease was reported by 75 (1.5%) patients, again most frequent in RA (N = 48, 1.9%). Overall, 696 (14.0%) IMID patients had ≥3 co-morbidities. Oral steroid use was highest in SARD (N = 166, 34.7%). The commonest DMARD in all groups was methotrexate, followed by sulfasalazine in RA (N = 379, 15.3%) and AxSpA-PsO (N = 189, 9.4%) and mycophenolate mofetil in SARDs (N = 69, 14.4%). Overall, 2079 (41.9%) IMID patients were receiving a biological DMARD. Conclusion A high proportion of IMID patients have more than one IMID diagnoses. Significant multi-morbidity with cardiovascular, respiratory and mood disorders was observed and considerable ongoing glucocorticoid usage. The IMID-Bioresource aims to refine patient subsets based on shared immune mechanisms to ultimately, improve precision medicine and patient outcomes. Disclosure S. Dyball: Grants/research support; MRC. Other; GSK, UCB. E. Vital: None. S. Plein: None. D. McGonagle: None. A.G. Pratt: None. J. Isaacs: None. B. Griffiths: None. W. Ng: None. J. McBeth: None. C.E.M. Griffiths: None. B. Parker: Honoraria; Fresenius-Kabi, AbbVie. Grants/research support; GSK, Genzyme/Sanofi. Other; Eli Lilly, Roche. M.H. Buch: None. I. Bruce: Consultancies; ILTOO, AstraZeneca, Eli Lilly, GSK, Merck Serono, UCB. Grants/research support; Genzyme/Sanofi, GSK, UCB, Roche. Other; AstraZeneca, GSK, UCB.