POS0755 PREVALENCE AND RELEVANCE OF ANTIBODIES AGAINST CITRULLINATED ALPHA ENOLASE (ANTI-CEP1) IN CONNECTIVE TISSUE DISEASES

Background:Anti-citrullinated alpha enolase antibodies have been investigated in rheumatoid arthritis and associated with bone erosion and interstitial lung disease but little is known about their prevalence and role in connective tissue diseases (CTDs).Objectives:The aim of this study was to investigate the prevalence and relevance of anti-CEP1 antibodies in CTDs.Methods:Serum samples from five independent patient cohorts were assessed: 1) established (est) primary Sjogren’s syndrome (pSS) N=78, 2) est-systemic lupus erythematosus (SLE) N=52, 3) est-systemic sclerosis (SSc) N=71, 4) pSS at disease onset N=30, 5) SLE at disease onset N=46 (cohorts 4 and 5 had at least 3 years of follow-up). Samples from ninety sex and age matched healthy donors (HD) and 200 patients with est-RA (disease controls) were also tested. Anti-CEP1 IgG antibodies were measured with a commercially available ELISA kit (Euroimmun, Luebeck, Germany).Results:Anti-CEP1 titer was significantly higher in est-pSS, est-SLE and est-SSc compared to HD, significantly lower in est-pSS and est-SSc compared to est-RA and comparable in est-SLE versus est-RA. We divided patients in every CTD group based on whether their anti-CEP1 titer was below or above the 25th, 50th and 75th percentile. In est-SLE anti-CEP1 values over the 25th percentile were associated with articular involvement (odds ratio, OR (95% confidence interval, CI)=11.5; 1.9-70.6, p=0.008). In est-pSS, no relationship between anti-CEP1>25th percentile and articular involvement was found but rather an association with rheumatoid factor positivity (OR (95% CI)=4.8, 1.6-14.1, p=0.004) and salivary gland swelling (OR (95% CI)=6.2, 1.3-29.1, p=0.021). In est-SSc no difference could be detected across the 3 groups. Anti-CEP-1 titers in pSS and SLE at onset did not differ from each other, were comparable also to those of HD and significantly lower than those of est-pSS, est-SLE and est-RA patients (all p<0.0001).). Of interest, we could retrieve a serum sample collected at the time of diagnosis for 5 patients from the cohort of established pSS and we observed that anti-CEP1 titers were significantly lower at pSS onset than during follow up (at least 12 months after the diagnosis, p=0.0024). No difference was observed in the clinical presentation at disease onset according to different anti-CEP1 titer and they did not predict the development of new clinical manifestations during follow-up.Conclusion:Anti-CEP-1 antibodies can be detected in CTDs at different title during the disease course and may increase overtime, at least in pSS. Although anti-CEP1 antibodies are associated with specific clinical manifestation in est-CTDs, such as articular involvement in est-SLE, they seem to lack a predictive value for future manifestations when measured at disease onset.References:[1]Alunno A, Bistoni O, Pratesi F et al Rheumatology (Oxford) 2018.[2]Manca ML, Alunno A, D’Amato C et al. Joint Bone Spine 2018.Disclosure of Interests:None declared

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FRI0565 PREVALENCE AND SIGNIFICANCE OF ANTIBODIES AGAINST CITRULLINATED ALPHA-ENOLASE (ANTI-CEP1) IN CONNECTIVE TISSUE DISEASES.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4549 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 885.2-885

Author(s):

A. Alunno ◽

F. Carubbi ◽

O. Bistoni ◽

M. Antonucci ◽

E. Bartoloni Bocci ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Lupus Erythematosus ◽

Bone Erosion ◽

Connective Tissue Diseases ◽

Serum Samples ◽

Erosive Disease ◽

Normal Controls

Background:Anti-cyclic citrullinated peptide (anti-CCP) auto-antibodies represent the current gold standard for the diagnosis of rheumatoid arthritis (RA). However, growing evidence suggests that a variety of other citrullinated self-proteins may act as autoantigens and lead to the production of autoantibodies (1). Furthermore, autoantibodies believed to be RA-specific have been detected also in patients with connective tissue diseases (CTDs). We recently demonstrated that antibodies against citrullinated alpha-enolase (anti-CEP1) are a biomarker of erosive disease and RA-associated interstitial lung disease (2).Objectives:The purpose of this study was to investigate the prevalence and possible prognostic value of anti-CEP-1 in patients with CTDs.Methods:Two hundred and twelve consecutive patients with CTDs (51 systemic lupus erythematosus (SLE), 85 primary Sjogren’s syndrome (pSS) and 76 systemic sclerosis (SSc)) were studied and compared to 97 sex and age matched normal controls (NC) and 267 patients with RA. Anti-CEP1 IgG were detected in serum samples with a commercial ELISA kit (Euroimmun).Results:The overall prevalence of anti-CEP1 in CTDs was 7% (15/212 patients). In detail, these antibodies were detectable in 4 out of 85 pSS (5%), 5 out of 51 SLE (10%) and 6/76 SSc (8%). The prevalence and the titer of anti-CEP1 in CTDs was significantly higher compared to NC and significantly lower compared to RA. Anti-CEP1 positive patients did not display a specific clinical and serological picture. Unlike in RA, anti-CEP1 did not correlate with CTD-associated ILD.Conclusion:This is the first study assessing anti-CEP1 in a large cohort of patients with CTDs. We demonstrated that the association of these autoantibodies with ILD is specific for RA since it is not observed in SLE, pSS and SSc. Furthermore, although being significantly more prevalent and at higher titer compared to NC, anti-CEP1 do not allow to discriminate different patient subsets displaying peculiar clinical or serological phenotypes. Based on our results, the application of anti-CEP1 in CTDs is not advisable, however larger studies may possibly identify correlations not evident in our cohort.References:[1] Bonifacio AF, Alunno A, La Paglia GMC, Valentini E, Leone MC, Bartoloni E, Gerli R. Novel autoantibodies in rheumatoid arthritis. Reumatismo 2019;71(1):1-12[2] Alunno A, Bistoni O, Pratesi F, La Paglia GMC, Puxeddu I, Migliorini P, Gerli R. Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in rheumatoid arthritis. Rheumatology (Oxford). 2018;57(5):850-855Disclosure of Interests:Alessia Alunno: None declared, Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Onelia Bistoni: None declared, Matteo Antonucci: None declared, Elena Bartoloni Bocci: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer, Roberto Gerli: None declared

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Pulmonary Hypertension Associated With Scleroderma and Connective Tissue Disease: Potential Molecular and Cellular Targets

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-16.2.61 ◽

2017 ◽

Vol 16 (2) ◽

pp. 61-67

Author(s):

Maria Trojanowska

Keyword(s):

Pulmonary Hypertension ◽

Connective Tissue ◽

Connective Tissue Disease ◽

Lupus Erythematosus ◽

Molecular Mechanisms ◽

Critical Role ◽

Connective Tissue Diseases ◽

Clinical Manifestations ◽

Response To Treatment ◽

Organ Systems

Systemic sclerosis (SSc) is characterized by autoimmunity, small-vessel vasculopathy, and fibrosis causing damage in multiple organ systems. Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of SSc, occurring in patients with the limited (lcSSc) and diffuse (dcSSc) forms of the disease and affecting 8% to 15% of patients.12 While pulmonary hypertension associated with connective tissue disease (CTD-PAH) has similar clinical features as idiopathic PAH, 1-year survival and freedom from hospitalization are lower in CTD-PAH.3 SSc-PAH has the worst 1-year survival rate at 82% compared with other connective tissue diseases, including systemic lupus erythematosus, mixed connective tissue disease, and rheumatoid arthritis.34 Despite the recent progress in the development of disease-targeted therapies, patients with SSc-PAH have a poorer response to treatment and a worse prognosis than other subgroups of PAH.1 Autoimmunity and prolonged vasculopathy preceding the development of clinical manifestations of SSc-PAH may play a critical role in the poorer outcome of SSc-PAH patients.1 This article will provide an overview of the recent findings related to cellular and molecular mechanisms associated with the development of PAH, with an emphasis on SSc-PAH.

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Decreased serum ACE2 levels in patients with connective tissue diseases

Rheumatology ◽

10.1093/rheumatology/keaa898 ◽

2020 ◽

Author(s):

Xiaojun Tang ◽

Linyu Geng ◽

Xuebing Feng ◽

Lingyun Sun

Keyword(s):

Connective Tissue ◽

Clinical Features ◽

Lupus Erythematosus ◽

Healthy Subjects ◽

Activity Index ◽

Connective Tissue Diseases ◽

Disease Activity Index ◽

Serum Samples ◽

Angiotensin Converting Enzyme 2 ◽

Activity Index Score

Abstract Objective To evaluate serum concentration and activity of angiotensin-converting enzyme 2 (ACE2) in patients with connective tissue diseases (CTDs). Methods Serum samples from healthy subjects and patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (SS) and rheumatoid arthritis (RA) were collected. The concentration and activity of ACE2 were measured by ELISA and fluorometric method respectively, and analyzed for associations with clinical features and concurrent medications. Results Totally 66 SLE, 55 SSc, 31 SS and 31 RA patients were involved. ACE2 concentration was significantly decreased in patients with either of the four CTDs compared with healthy subjects. The concentration was not linked to special clinical features expect that it was slightly lower in patients with lupus nephritis than those without. In SLE patients, ACE2 concentration elevated with the increase of glucocorticoids, and was not associated with other treatments. Different from the concentration, ACE2 activity was increased in CTD patients. A weak correlation of ACE2 activity with SLE disease activity index score was also observed. Conclusion The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggests ACE2 levels are not affected by most of the treatments.

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POS0789 APPLICATION OF THE NEW ACR/EULAR 2019 CLASSIFICATION CRITERIA OF SYSTEMIC LUPUS ERYTHEMATOSUS TO A INCEPTION, MONOCENTRIC COHORT OF UNDIFFERENTIATED CONNECTIVE TISSUE DISEASES POPULATION AT ONSET OF THE DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3909 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 647.1-647

Author(s):

E. Elefante ◽

A. Parma ◽

V. Nannipieri ◽

V. Signorini ◽

C. Stagnaro ◽

...

Keyword(s):

Connective Tissue ◽

Lupus Erythematosus ◽

Connective Tissue Diseases ◽

Classification Criteria ◽

Inception Cohort ◽

Systemic Lupus ◽

New Classification ◽

Undifferentiated Connective Tissue Diseases ◽

Over Time

Background:undifferentiated connective tissue diseases (UCTDs) are a group of systemic autoimmune diseases that share clinical and serological manifestations with definite connective tissue diseases (CTDs), but do not satisfy existing classification criteria1. Within this group, it is possible to identify very heterogeneous conditions: transitory and self-limiting forms, stable conditions over time and forms that will evolve towards definite CTDs, in particular Systemic Lupus Erythematosus (SLE). The availability of new classification criteria for CTDs could be useful in identifying major CTDs from their onset and help in the differentiation from stable UCTDs, which will maintain their undifferentiated profile over time.Objectives:the aim of this study was to apply the new ACR/EULAR 2019 classification criteria of SLE2 to patients included, at the onset of UCTD, to evaluate how many patients could be re-classified as SLE.Methods:this is a retrospective observational study that enrolls patients who received the diagnosis of UCTD at the Rheumatology Unit of Pisa, according to the classification criteria proposed by Mosca et al1, and were then regularly followed in the same clinic (inception cohort). For each patient, demographics, comorbidities, treatment, clinical and serological data were collected, at baseline and during follow-up. The new ACR/EULAR 2019 classification criteria of SLE were applied to the inception cohort at the onset of the disease. The characteristics of patients re-classified as SLE according to the new classification criteria and those of patients who “remained” classified as UCTD were compared.Results:we enrolled 202 patients with a diagnosis of UCTD, mainly female (F:M 193:9) and of Caucasian ethnicity (97.5%), mean age at the diagnosis 38,5 ± 13,2 years and a median follow-up of 5 years (IQR 2-10).During the follow-up, 10 patients (4.9%) in our cohort developed clinical and serological characteristics that led to a diagnosis of a definite CTD, in particular: 7 SLE, 2 Mixed Connective Tissue Disease (MCTD) and 1 Sjogren’s syndrome.Applying the ACR/EULAR 2019 classification criteria of SLE to patients enrolled at the onset of the disease, 38/202 (18.8%) would have been classified as SLE (with a median score of 12 (IQR 11-15)) on the basis of the presenting clinical and serological manifestations. Interestingly, 6/7 patients who received a diagnosis of SLE during the follow-up were among these 38 patients.Among the items of the new classification criteria of SLE, the most frequently satisfied by patients “re-classified” were arthritis (63.2%), hematological (44.7%) and skin (23.7%) manifestations; as for the “immunological” items, hypocomplementemia (71%), SLE-specific (52.6%) and antiphospholipid (35.1%) autoantibodies.Comparing the subgroup of patients “re-classified” as SLE with that of patients who “remained” UCTD, we found that the first group presented more frequently hematological manifestations, hypocomplementemia and anti-dsDNA, anti-Sm, anti-RNP, anti-beta2GPI positivity at the onset of the disease (p<0.01). Moreover, during the follow-up, the subgroup of patients “re-classified” as SLE developed more frequently malar (p<0.05) and discoid rash and arthritis (p<0.01) compared to patients who “remained” UCTD.Conclusion:The development of increasingly sensible and specific classification criteria for definite CTDs may guide in the identification of stable UCTDs since their early stages and consequently in better definition of these conditions that can be considered as a distinct clinical entity.The early identification of stable UCTD is of great importance not only for clinical management (follow-up schedules as well as therapeutic protocols) but also for scientific implications.References:[1]Mosca M. et al., Clin Exp Rheumatol. Sep-Oct 1999;17(5):615-20; 2. Fanouriakis A. et al., Ann Rheum Dis. 2020 Jun;79(6):713-723.Disclosure of Interests:None declared

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New Coupled-Particle Light-Scattering Assay for Detection of Ro/SSA (52 and 60 Kilodaltons) and La/SSB Autoantibodies in Connective Tissue Diseases

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.8.5.922-925.2001 ◽

2001 ◽

Vol 8 (5) ◽

pp. 922-925 ◽

Cited By ~ 13

Author(s):

Nicola Bizzaro ◽

Fabrizio Bonelli ◽

Elio Tonutti ◽

Renato Tozzoli ◽

Danilo Villalta

Keyword(s):

Light Scattering ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Prokaryotic Expression ◽

Viral Infections ◽

Recombinant Dna ◽

Expression System ◽

Connective Tissue Diseases ◽

Serum Samples ◽

Prokaryotic Expression System

ABSTRACT The diagnostic and analytical performance of the coupled-particle light-scattering assay in detecting anti-Ro/SSA autoantibodies (the 60-kDa [Ro60] and the 52-kDa [Ro52] antibodies) and anti-La/SSB autoantibodies was evaluated. The antigens were obtained by recombinant DNA procedures to include the most immunogenic epitopes for each protein by using a prokaryotic expression system. Serum samples from 151 patients with connective tissue diseases and 52 control subjects (including patients with viral infections, patients with Lyme disease, and healthy subjects) were studied. Sensitivities for detection of anti-Ro/SSA and anti-La/SSB were 88.2 and 95.2%, respectively; specificities were 97.6 and 98.1%, respectively. The intra-assay coefficient of variation (CV) ranged from 4.3 to 10.9% for anti-Ro/SSA and from 2.8 to 12.5% for anti-La/SSB; interassay CVs ranged from 6.5 to 13.2% and from 8.2 to 14.5%, respectively. Among the anti-Ro/SSA-positive samples, Ro60 was recognized by 66% of the test sera and Ro52 was recognized by 95% of the test sera. Thirty-four percent of the Ro/SSA-positive sera were reactive only with the Ro52 antigen, indicating that anti-Ro52 is the most common antibody specificity recognized by anti-Ro/SSA autoantibodies. No differences were found between the prevalences of anti-Ro60 and anti-Ro52 in relation to systemic lupus erythematosus or Sjögren's syndrome. The results of the present study indicate that this new immunoassay is an efficient diagnostic tool for the detection of anti-Ro/SSA and anti-La/SSB antibodies in patients with autoimmune disorders.

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Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽

10.1177/09612033211014253 ◽

2021 ◽

pp. 096120332110142

Author(s):

Tamer A Gheita ◽

Rasha Abdel Noor ◽

Esam Abualfadl ◽

Osama S Abousehly ◽

Iman I El-Gazzar ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Age Of Onset ◽

Wide Spectrum ◽

Age At Onset ◽

Disease Onset ◽

Clinical Manifestations ◽

Population Based ◽

Systemic Lupus ◽

Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

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AB0702 PITFALLS IN THE DIAGNOSIS OF COVID-19 – EXPERIENCES FROM A RHEUMATOLOGY OUTPATIENT CLINIC

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3798 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1383.2-1383

Author(s):

S. G. Werner ◽

H. E. Langer ◽

P. Höhenrieder ◽

R. Chatelain

Keyword(s):

Outpatient Clinic ◽

Virus Disease ◽

Disease Onset ◽

Signs And Symptoms ◽

Contact Tracing ◽

Igg Antibodies ◽

Antibody Testing ◽

Antibody Titers ◽

Rheumatology Outpatient

Background:PCR (Polymerase Chain Reaction) is generally considered the gold standard for confirming the diagnosis in the early stages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. However, in our rheumatology outpatient clinic we observed a significant discrepancy between clinical evidence of COVID-19 and PCR results.Objectives:Aim of this retrospective study was to analyze the significance of PCR and serologic tests in the diagnosis of COVID-19 (Corona Virus Disease 2019) in a cohort of patients with rheumatic diseases.Methods:Between March 2020 and January 2021, 35 patients with a history of established COVID-19 or typical signs and symptoms were identified on the occasion of a routine rheumatology follow-up examination in our institution. Previous diagnostic work-up in external facilities (results of PCR or antibody testing, imaging) was documented. Antibody ELISA-tests (IgG, IgA, IgM, Euroimmun) were performed in patients reporting typical signs and symptoms of COVID-19 in the past.Results:PCR diagnostics had been performed in 15/35 patients (43%), in 13/35 (39%) at the onset of the first symptoms, in 2 subjects only 2 months later. PCR was positive in 7/13 (54%) of those tested early, but negative in the two patients tested later. In 29/35 patients (83%) SARS-CoV-2-ELISA tests were performed on the occasion of the routine rheumatologic examination (interval between first symptoms and testing on average 98 days, median86, range 4-283 days). In two of the initially negative individuals the second PCR was positive. ELISA tests were positive in all patients. SARS-CoV-2 IgM antibodies were positive in only two patients (however 55 and 71 days after disease onset), n=8/29 (28%) IgG only, n=9/29 (31%) IgG and IgA, n=12/29 (41%) IgA only. In these subjects, IgG antibodies did not develop even in the further course. Antibody titers were in part very high, but in part also very low (only just above the normal value), so even low titers were diagnostic obviously. In all patients with negative PCR, ELISA was positive and retrospectively led to confirmation of the diagnosis. Only in 13/35 patients (37%) diagnosis had been made with the onset of the first symptoms or in the course of clinically manifest disease and had led to appropriate quarantine measures and contact tracing by the health authorities. In contrast, in the majority of patients (63%), the diagnosis of COVID-19 infection was only made retrospectively on the occasion of a routine rheumatologic follow-up. However, 5 of these 22 patients (23%) had quarantined themselves during the symptomatic phase. Titer histories were available from 12 patients. The titer became negative in 7 patients, after a mean of 188 days (median 202, min 51, max 296 days), and remained positive in 5 individuals (mean 190 days, median 191, min 122, max 260 days). The change of the titer was independent of disease severity or antirheumatic therapy.Conclusion:The results suggest that the importance of PCR in the diagnosis of COVID-19 may be overestimated. Therefore, antibody testing for SARS-CoV-2 should be performed in cases of clinical suspicion and negative PCR. In antibody diagnostics, special features were observed compared to other viruses, in particular, in some patients only low antibody titers or the absence of seroconversion with lack of development of IgG antibodies. Normalization of antibody titers in some patients supports the recommendation to vaccinate even after expired COVID-19 disease.Disclosure of Interests:None declared

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AB0815 FIRST DEGREE RELATIVES OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS - CLINICAL, SEROLOGICAL AND IMMUNOLOGICAL CORRELATIONS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.511 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1432.2-1432

Author(s):

B. Penev ◽

G. Vasilev ◽

D. Kyurkchiev ◽

S. Monov

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Current Knowledge ◽

Statistical Significance ◽

Clinical Signs ◽

Connective Tissue Diseases ◽

Pharmaceutical Products ◽

Systemic Lupus

Background:Antinuclear antibodies (ANA) have been unequivocally recognized as essential for diagnosis and play both pathogenic and diagnostic roles in systemic lupus erythematosus (SLE). SLE and ANA have also been found to be more often among relatives of SLE patients. ANA and other immunological changes are known to appear prior to the clinical onset of the disease and thus can be used as predictors. Studies have reported that relatives of SLE patients who later transitioned to SLE displayed more lupus-associated autoantibody specificities and had early clinical signs. They also displayed elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS) and interferon-associated chemokines, with concurrent decreases in levels of regulatory mediators, e.g. tumor growth factor (TGF)-β. Commonly recognized risk factors for SLE are signs of past Epstein-Barr (EBV) infection, use of estrogen drugs and current smoking. It seems that ANA, immunologic changes and risk factors have not been investigated together in relatives of SLE patients.Objectives:The aim of the study was to determine the relative prevalence of clinical signs of SLE or connective tissue disease (CTD), smoking, use of estrogen drugs and levels of circulating ANA, BLyS, IFN-α, TGF-β, anti-EBV viral capsid antigen (VCA) IgM and IgG antibodies among sera of FDR, non-FDR healthy individuals and SLE patients.Methods:Forty three FDRs of SLE patients were studied along with 15 SLE patients and 15 clinically healthy subjects as control groups. The FDRs and the healthy answered a questionnaire about early clinical signs of CTD, smoking and estrogen use history. The questionnaire was developed based on the existing Screening Questionnaire for Connective Tissue Diseases and current knowledge of most early signs of CTD. Blood samples were obtained and tested for ANA, both by indirect immunofluorescence and immunoblot, anti-dsDNA by ELISA. ELISA was also performed to measure levels of BLys, IFN-α, TGF-β, anti-EBV IgM and IgG.Results:More than half of the FDRs displayed ANA in titer 1:160 or more, with predominately AC-4 type of fluorescence according to International Classification on ANA Patterns (ICAP) compared to only AC-1 and AC-0 among patients and controls respectively. A correlation between the ANA titer and the number of complaints was found. This was particularly valid or reported skin complaints and oral ulcers which appeared more frequently when ANA was 1:320 or above (p=0,018 and 0,038 respectively). Furthermore, oral ulcerations showed positive correlation with the presence of anti-Ro60. No associations were found in the healthy group between reported complaints and ANA titers. Smoking and estrogen use did not differ across the three groups. Patients showed significant differences in levels of BLys (p=0,027), TGF-β (p=0,019) and anti-EBV IgG (p=0.041) compared to both FDRs and controls. Without reaching statistical significance, levels of TGF-β tend to split the FDR group into “healthy-like” and “SLE-like”.Conclusion:Our results show that FDR ANA levels are between those of SLE patients and healthy subject groups. This is consistent with previous studies. The data also suggest that ANA positivity correlates with reported complaints, some of which could be interpreted as very early clinical signs of SLE. Of note, anti-Ro60 is known to be among the earliest ANA that appear in “future” SLE patients and in this study they are related to oral complaints that could be caused by early sicca phenomena. Immunologically, our data support previous findings [1] that the FDRs are a heterogenic group with different “lupus-developing” potential.References:[1]Munroe МE. et al, Soluble Mediators and Clinical Features Discern Risk of Transitioning to Classified Disease in Relatives of Systemic Lupus Erythematosus Patients, Arthritis Rheumatol. 2017 March; 69(3): 630–642.Disclosure of Interests:Bogdan Penev: None declared, Georgi Vasilev: None declared, Dobroslav Kyurkchiev: None declared, Simeon Monov Speakers bureau: I have been paid for giving lectures on statistical data on efficacy of many pharmaceutical products on various companies

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