Autoantibodies Detected in MIS-C Patients due to Administration of Intravenous Immunoglobulin

The autoantibody profile associated with known autoimmune diseases in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that adults with COVID-19 had a moderate prevalence of autoantibodies against the lung antigen KCNRG, and SLE-associated Smith autoantigen. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute insulin-dependent diabetes. While autoantibodies associated with SLE/Sjogren syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Together these findings demonstrate that administration of high-dose IVIG is responsible for the detection of several autoantibodies in MIS-C and KD. Further studies are needed to investigate autoantibody production in MIS-C patients, independently from IVIG administration.

Distribution of ANA Pattern and Autoantibody Profile in Various Autoimmune Disorders -A Tertiary Care Centre Experience.

Background: Type of antibodies produced by an individual in response to any autoimmune disorder varies from person to person and from place to place depending upon the immune status of the patient . Aims & objectives: To describe the fluorescence pattern of ANA by indirect immunofluorescent assay in patients with autoimmune diseases and compare it with their ANA profile. Material & Methods: In this retrospective study (January 2018 to December 2020) we reviewed the case records of 96 patients with different autoimmune diseases. Their demographic details like age, gender, family history, presenting symptoms were tabulated. We compared their respective ANA test reports (Pattern and profile) Results: Data of 96 patients (20 male and 76 females) was analyzed. The age range of the study cohort was 10- 77 years , mean age was 39.53 .There were 23(23.9%) patients with SLE, 34(35.4%) with MCTD . 6 (6.2%) Sjogren's syndrome. Glomerulonephritis was present in 7(7.2%) patients and Rheumatoid arthritis in 4 (4.1%) . All study participants had ANA positive and ANA pattern was seen as homogenous in 34(35.4%), speckled 45(46%), nuclear pattern was seen in 33(34.9%) . LIA was found to be significantly positive in sjogren's disease while in SLE only 22 patients had positive LIA. None of our Rheumatoid arthritis patients had positive LIA Conclusion: We conclude that it is better to restrict performing line immunoassays as these are expensive and use ANA-IIF fluorescent patterns to predict presence of autoantibodies to diagnose an autoimmune disease.

Autoimmunomic Signatures of Aging and Age-Related Neurodegenerative Diseases Are Associated With Brain Function and Ribosomal Proteins

Biological aging is a complex process featured by declined function of cells and tissues, including those of the immune system. As a consequence, aging affects the expression and development of autoantibodies and autoreactive T cells, which can be seen in their sum as the autoimmunome of an individual. In this study we analyzed whether sets of autoimmune features are associated with specific phenotypes which form autoimmunomic signatures related to age and neurodegenerative diseases. The autoantibody profile data of healthy subjects and patients from the GEO database was used to explore autoimmunomic signatures of aging and three neurodegenerative diseases including Parkinson's disease (PD), Alzheimer disease (AD) and Multiple Sclerosis (MS). Our results demonstrate that the autoimmunomic signature of aging is featured by an undulated increase of IgG autoantibodies associated with learning and behavior and a consistent increase of IgG autoantibodies related to ribosome and translation, and the autoimmunomic signature of aging are also associated with age-related neurodegenerative diseases. Intriguingly, Differential Expression-Sliding Window Analysis (DE-SWAN) identified three waves of changes of autoantibodies during aging at an age of 30, 50, and 62 years, respectively. Furthermore, IgG autoantibodies, in particular those against ribosomal proteins, could be used as prediction markers for aging and age-related neurodegenerative diseases. Therefore, this study for the first time uncovers comprehensive autoimmunomic signatures for aging and age-related neurodegenerative diseases.

POS0725 CLINICAL AND IMMUNOLOGICAL CHARACTERISTICS OF PATIENTS WITH JUVENILE-, ADULT- AND LATE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Systemic lupus erythematosus (SLE) predominantly develops in women of child-bearing age. However, nearly 20% of cases present during childhood, generally after puberty (juvenile-onset SLE, JSLE). On the other hand, 10-20% of patients develop SLE after the age of 45-50 years (late-onset SLE, LSLE) [1]. It is known that age at disease onset can influence the clinical presentation and course of SLE, but the findings are not always consistent across the studies [2].Objectives:The aim of this study was to evaluate the spectrum of clinical manifestations and autoantibody profile in patients with SLE in the central region of Ukraine regarding age at onset.Methods:The study included 258 SLE patients before starting an adequate therapy, comprising 225 females (87.2%) and 33 males (12.8%). The median age at SLE onset was 28 (20-39) years. The patients were classified into 3 groups: I – age at SLE onset ≤18 years (JSLE; n=52; 20.2%), II – SLE onset at age 19-44 years (adult-onset SLE, ASLE; n=161; 62.4%), III – age at disease onset ≥45 years (LSLE; n=45; 17.4%). The clinical and demographic data, SLE Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and autoantibody profile were analyzed. Quantitative and categorical data were compared using Kruskal-Wallis test and chi-square test, respectively.Results:There was a difference in prevalence of malar rash between the groups (p=0.022): it was more common in JSLE (40.4%) and ASLE (34.4%) than in LSLE patients (15.6%; p=0.04 and 0.05, respectively). Similar distribution was found for renal involvement: JSLE and ASLE patients presented higher rates of nephritis (55.8% and 49.4%, respectively) than LSLE patients (23.8%; p=0.012 and 0.014, respectively). But the groups did not differ significantly with regard to nephrotic syndrome (p=0.224). ASLE was associated with more frequent alopecia (38.8%) comparing with JSLE (19.2%; p=0.04). Moreover, ASLE patients also had the highest frequency of lymphadenopathy (56.3%) whereas in LSLE it was observed only in 25.0% of patients (p=0.001). Serositis was more common in LSLE (54.5%) and ASLE (43.8%) than in JSLE (23.1%; p=0.011 and 0.034, respectively). Although secondary Sjögren’s syndrome was more frequently observed in ASLE (7.6%) and LSLE (7.3%) than in JSLE (0.0%), the difference did not achieve statistical significance (p=0.157). Also, no differences were observed in the occurence of arthritis, pulmonary and neurological manifestations, constitutional symptoms, SLEDAI score among the groups. Median CRP level in LSLE was significantly higher (14.0 (1.1-46.4) mg/L) than in JSLE (0.7 (0.0-12.0) mg/L) (p<0.05). But all groups did not differ significantly with regard to ESR levels. When differences in antinuclear antibodies were analyzed, we disclosed that the frequency of anti-dsDNA positive results was significantly higher in JSLE (68.6%) and ASLE (70.1%) patients when compared with that found in LSLE patients (31.3%) (p=0.016 and 0.001, respectively). There were no significant differences between groups with regard to positivity for other antibodies (anti-Sm, -Ro, -La, -RNP, antiphospholipid antibodies).Conclusion:JSLE and ASLE patients are more likely to have malar rash, nephritis and anti-dsDNA positivity. Alopecia and lymphadenopathy are most frequent in ASLE patients. JSLE are far less likely to have serositis than any other group. Patients with LSLE demonstrate comparatively low frequency of major organ involvement, but they have higher levels of CRP.References:[1]Ambrose N., et al. Differences in disease phenotype and severity in SLE across age groups. Lupus. 2016;25(14):1542-1550.[2]Livingston B., et al. Differences in autoantibody profiles and disease activity and damage scores between childhood- and adult-onset systemic lupus erythematosus: a meta-analysis. Seminars in Arthritis and Rheumatism. 2012;42(3):271-280.Disclosure of Interests:None declared

POS0457 CHANGES OF RF ISOTYPE PROFILE IN PATIENTS WITH RHEUsMATOID ARTHRITIS: DATA FROM 10 YEARS FOLLOW-UP STUDY

Background:Presence of autoantibodies such as anti-cyclic citrullinated peptide (anti-CCP2) and rheumatoid factor (RF) is of considerable diagnostic and prognostic value in patients with rheumatoid arthritis (RA). Limited data are available for autoantibody profile changes over time in patients with RA.Objectives:Thus, we compared the presence of anti-CCP2 and different RF isotypes in individual RA patients at baseline and during 10 years follow-up.Methods:A total of 320 RA patients from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study was included in this study. The presence of anti-CCP2, IgM RF, IgG RF, and IgA RF at baseline and at later time point (±10 years) were determined using enzyme-linked immunosorbent assays, with identical techniques in paired samples. Seropositive RA is defined by the presence of at least one autoantibody, whilst seronegative RA is defined by the absence of all investigated autoantibodies.Results:The proportion of seropositive RA were higher for the follow-up samples (n=263, 82.2%) as compared to the baseline samples (n=251, 78.4%). Among the baseline samples, 105 (41.8%) were positive for anti-CCP2 and all RF isotypes. Of these individuals, 85 (81.0%) remained positive for all antibodies at the follow-up, while 20 (19.0%) lost one or more RF isotypes (4 IgM RF, 19 IgG RF and 13 IgA RF). Interestingly, 14 (5.6%) RA patients who were seropositive at baseline became totally seronegative after follow-up. Among the 69 patients seronegative at baseline, 26 (37.7%) acquired one or more autoantibodies at follow-up (14 IgM RF, 2 IgG RF, 9 IgA RF and 8 anti-CCP2) (Figure 1).Conclusion:Anti-CCP2 present at baseline usually remained at follow-up. Among Malaysian RA patients, changes in status were mainly found for RF of all isotypes.References:[1]Barra, Lillian et al. “Lack of seroconversion of rheumatoid factor and anti-cyclic citrullinated peptide in patients with early inflammatory arthritis: a systematic literature review.” Rheumatology (Oxford, England) vol. 50,2 (2011): 311-6.[2]van Delft, Myrthe A M, and Tom W J Huizinga. “An overview of autoantibodies in rheumatoid arthritis.” Journal of autoimmunity vol. 110 (2020): 102392.Figure 1.Comparison of serum autoantibody profile in rheumatoid arthritis patients during baseline enrolment and 10 years follow-up.Acknowledgements:The authors would like to thank the Director General of Health, Ministry of Health Malaysia for supporting this study. The authors are also indebted to participants for their kind participation. This study was financially supported by the Ministry of Health, Malaysia (JPP-IMR 08-012; 18-051).Disclosure of Interests:None declared

OP0041 SALIVA AND SERUM LEVELS OF CXCL13: ASSOCIATION WITH THE SEVERITY OF SALIVARY GLAND LESIONS AND LYMPHOMA IN PATIENTS WITH SJÖGREN’S SYNDROME (SS)

Background:CXCL13 has been implicated in the formation of ectopic germinal centers (GC) in minor salivary gland (MSG) inflammatory lesions of SS patients. Recent studies suggest that serum CXCL13 levels associate with disease severity and risk for non-Hodgkin’s lymphoma (NHL) development.Objectives:To validate the clinical utility of CXCL13 by investigating potential associations of saliva and serum CXCL13 levels with various histopathologic (including severity of MSG autoimmune infiltrates and GC formation), serologic and clinical features of the disease, as well as NHL.Methods:CXCL13 levels were measured by a commercially available ELISA (sensitivity: 1 pg/ml; Abcam, Cambridge, UK) in paired serum and saliva specimens from 25 SS patients (9 with NHL; SSL), 9 sicca controls (SC; sicca-complaining individuals with no infiltrates in diagnostic MSG biopsy and negative autoantibody profile) and 6 healthy controls (HC). From the 16 SS patients without evidence of NHL, 5 had mild, 6 intermediate and 5 severe lesions at MSGs, as arbitrarily defined by focus (FS) and Tarpley (TS) biopsy scores (mild: FS:1-1.7, TS:1, intermediate: FS:1.8-2.95, TS:2 and severe: FS: 3.0-11, TS: 3-4). Furthermore, the organization of the MSG infiltrates to GCs has been evaluated in 23 patients revealing 10 with GCs.Results:Kruskal-Wallis analysis revealed that serum CXCL13 levels were significantly increased in SS patients without or with NHL (median: 94.83 pg/ml and 96.70 pg/ml, respectively), compared to SC and HC (35.44 and 40.92 pg/ml respectively; p<0.05), whereas saliva levels were only marginally increased (76.47, 84.10, 55.98 and 65.30 pg/ml in SS, SSL, SC and HC, respectively, p=0.051). Among SS patients with distinct MSG lesion severity, only those with severe lesions were found to express significantly higher serum CXCL13 levels (149.3 pg/ml) from SC and HC (p: 0,0051 and 0.0166, respectively). Spearman’s Rank correlation analysis showed that both serum and saliva levels correlated with SG biopsy focus score (r: 0.6889, p=0.0001 and r: 0.4222, p=0.01, respectively). Mann-Whitney test revealed that serum CXCL13 levels were significantly elevated in patients with GCs at MSG lesions (156.1 vs 69.64 pg/ml, p:0.0015), rheumatoid factor (105.0 vs 53.72 pg/ml, p: 0.015) and marginally with anti-Ro/La antibodies (121.8 vs 65.05 pg/ml, p: 0.06) compared to those without. Furthermore, CXCL13 levels were significantly increased in SS patients at high risk to develop NHL compared to low risk (149.3 vs 71.54 pg/ml, respectively, p: 0.0275). Saliva levels were not found to associate with the studied features.Conclusion:Serum and to a lesser extend saliva CXCL13 levels are increased in SS and SSL patients and associate with the degree of MSG infiltration, as assessed by focus score. Serum, but not saliva, CXCL13 associates with various disease features, including GC formation, and may have a clinical utility in identifying SS patients at high risk to develop lymphoma.Disclosure of Interests:None declared

Autoantibodies to speckled protein family in primary biliary cholangitis

The autoantibody profile of primary biliary cholangitis (PBC) includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in more than 50% of PBC patients. One of the two immunofluorescence patterns which are historically considered “PBC-specific” is the so-called “multiple nuclear dots” (MND) targeting nuclear body proteins such as Sp100, Sp140, Sp140L proteins, promyelocytic leukemia protein (PML) and small ubiquitin-related modifier proteins (SUMO). It has been hypothesized a role of nuclear body protein alterations in immune disorders such as PBC, thus suggesting novel and more refined therapeutic approaches.

Palindromic Rheumatism: Just a Pre-rheumatoid Stage or Something Else?

Palindromic rheumatism (PR), a unique clinical entity, has a characteristic clinical presentation with a relapsing/remitting course. It is established that most patients with PR evolve to chronic disease, of which rheumatoid arthritis (RA) is by far the most common. The relationship between PR and RA is unclear, with similarities and differences between the two, and not all patients evolve to RA in the long-term. Therefore, PR is clearly a pre-RA stage for most, but not all, patients. Autoimmunity plays a substantial role in PR, with the same characteristic autoantibody profile observed in RA, although with some differences in the immune response repertoire. Autoinflammation may also be relevant in some cases of PR. Prognostic factors for RA progression are identified but their exact predictive value is not clear. There are several unmet needs in PR, such as the diagnostic criteria and clinical case definition, the pathogenic mechanisms involved in the unusual clinical course, and the evolution to RA, and our understanding of the therapeutic strategy that could best avoid progression to persistent and potentially destructive arthritis.