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Objectives Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients. Methods Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M of aPS/PT, anti-cardiolipin and anti-β2glycoprotein I (anti-β2GPI) were tested in both cohorts, and lupus anticoagulant (LA) also in the Swedish cohort. Clinical antiphospholipid syndrome-related events and atherosclerosis, measured as carotid plaques were assessed for associations. Univariate and multivariate analyses adjusting for cardiovascular risk factors were performed. Results Sudanese SLE patients had higher levels of IgM aPS/PT, but using national cut-offs, the frequency of positivity was similar to Swedish patients for all isotypes. Among Swedish patients, all isotypes of aPS/PT associated with venous thromboembolism (VTE), while only IgA aPS/PT associated with arterial thrombosis (AT). aPS/PT antibodies associated strongly with LA and they were, independently, the best predictor for VTE. Double positivity for aPS/PT and anti-β2GPI associated with higher VTE risk than the conventional triple positivity. Carotid plaques did not associate with any antiphospholipid antibody. Conclusions IgA aPS/PT associated with AT, and the association of IgG/M aPS/PT with VTE outperforms LA and criteria antiphospholipid antibodies in Swedish SLE patients. Furthermore, double positivity for aPS/PT and anti-β2GPI performed better than conventional triple positivity. Future studies need to address if aPS/PT can replace LA, as this would simplify clinical procedures.

Objective The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities. Methods Healthy Sudanese pregnant women ( n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females. Results Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI ( p 2GPI (both assays; p 2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased. Conclusions IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

Objectives IgA antiphospholipid antibodies (aPL) are prevalent in systemic lupus erythematosus (SLE) patients of African American, Afro-Caribbean and South African origin. Nevertheless, data from North Africa are lacking, and most studies use manufacturer-suggested cut-offs based on Caucasian controls. Therefore, we compared aPL isotypes in Sudanese and Swedish SLE patients using nation-based cut-offs. Methods Consecutive SLE patients and age- and sex-matched controls from Sudan ( N = 115/106) and Sweden ( N = 340/318) were included. All patients fulfilled the 1982 American College of Rheumatology SLE classification criteria. Antiphospholipid syndrome–related events were obtained from patients’ records. IgA/G/M anticardiolipin and anti-β2 glycoprotein I (β2GPI) were analysed with two independent assays. IgA anti-β2GPI domain 1 (D1) was also investigated. Manufacturers’ cut-offs and the 95th and 99th percentile cut-offs based on national controls were used. Results Sudanese patients and controls had higher levels and were more often positive for IgA aPL than Swedes when using manufacturers’ cut-offs. In contrast, using national cut-offs, the increase in IgA aPL among Sudanese patients was lost. Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and did not associate with aPL. No clinical associations were observed with IgA anti-β2GPI in Sudanese patients. Thromboses in Swedes were associated with IgG/M aPL. Fetal loss was associated with aPL in both cohorts. Conclusions IgA anti-β2GPI prevalence was higher among Sudanese compared to Swedish patients when manufacturers’ cut-offs were used. This situation was reversed when applying national cut-offs. Anti-D1 was not increased in Sudanese patients. Previous studies on populations of African origin, which demonstrate a high prevalence of IgA aPL positivity, should be re-evaluated using a similar cut-off approach.

Background Recent studies have shown divergent associations between rheumatoid arthritis (RA)-associated autoantibodies and RA onset phenotype. Whereas some studies report more inflammation in seronegative patients [1, 2], others report that rheumatoid factor (RF) associates with high baseline disease activity [3]. Objectives To define how individual RA-associated autoantibodies associate with individual disease activity score (DAS28, DAS28CRP) components at the time of RA diagnosis. Methods Sixteen individual ACPA reactivities, anti-CCP2, IgA-, IgG- and IgM-RF were analyzed centrally in baseline sera from 1600 RA patients classified according to the 1987 ACR criteria. All antibody cut-offs were determined as the 98th percentile among controls. The results were related to CRP, ESR, number of swollen and tender joints, DAS28, DAS28CRP, global disease activity (visual analogue scale), and health assessment questionnaire obtained at baseline. Results Individually, anti-CCP2, IgA RF and IgM RF associated with low counts of swollen and tender joints, with strongest association to anti-CCP2, and with high ESR. The association to low joint counts was stronger to number of individual ACPA reactivities than to anti-CCP2 levels (table). In multiple regression adjusted for age, sex and inclusion year, ACPA number associated strictly with low joint counts whereas IgM RF level associated with increased inflammatory markers, especially ESR (table). Also among IgM RF negative patients, occurrence of ACPA associated with low swollen and tender joint counts. Contrary, among ACPA negative patients, IgM showed no association to elevated ESR. The effect of RF on ESR increased with the number of individual ACPA reactivities present, most prominently for IgM RF (figure). Conclusion In early RA, ACPA associate with low counts of affected joints and IgM RF associates with elevated ESR in an ACPA-dependent manner. The latter finding relates to in vitro studies showing enhanced inflammatory effect of ACPA immune complexes with addition of RF[4, 5]. Future RA studies relating autoantibodies to disease activity may benefit from evaluating the impact of individual antibodies as well as distinct DAS components separately. References [1] Barra L, et al. J Rheumatol 2014;41:2361. [2] Nordberg LB, et al. Ann Rheum Dis 2017;76:341. [3] Aletaha D, et al. Arthritis Res Ther 2015;17:229. [4] Laurent L, et al. Ann Rheum Dis 2015;74:1425. [5] Sokolove J, et al. Arthritis Rheumatol 2014;66:813. Disclosure of Interests Eleftheria Pertsinidou: None declared, Vivek Anand Manivel: None declared, Lars Klareskog Grant/research support from: Yes, but not for the presented study., Lars Alfredsson: None declared, Linda Mathsson Employee of: employed by Thermo Fisher Scientific, Monika Hansson: None declared, Martin Cornillet: None declared, Guy Serre: None declared, Rikard Holmdahl: None declared, Karl Skriner: None declared, Per-Johan Jakobsson: None declared, Helga Westerlind: None declared, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Saedis Saevarsdottir Employee of: Part-time employee at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project., Johan Ronnelid: None declared

Background IgM RF and anti-CCP2 have been shown to associate with young age at RA diagnosis [1, 2]. By contrast, little is known about the association between other RF isotypes and age at onset, or sex. Objectives To examine the association between individual RA autoantibodies, sex and age at RA onset. Methods Anti-CCP2, IgA-, IgG- and IgM-RF were analysed centrally in baseline sera from 1600 Epidemiological Investigations in RA (EIRA) patients aged 18-70 years and classified according to the 1987 ACR criteria within one year of first symptoms. Cut-offs for RF isotypes were determined at the 98th percentile based on the EIRA RA-free controls, close to the 98.4% anti-CCP2 specificity. Results Anti-CCP2, IgA-, IgG- and IgM RF were found in 1020 (64%), 692 (43%), 529 (33%), and 916 (57%), of the patients, respectively. Mean (median) age at diagnosis among men was 54 (57) year, higher than 51 (54) years among women (p Conclusion On average, IgA RF positive (vs. negative) RA patients are almost four years older at the time of diagnosis; the opposite was found for anti-CCP2 and IgM RF. Whereas sex-differences explain the age-association for IgM RF, this is not the case for anti-CCP2 and for IgA RF. References [1] Diaz FJ, et al. Joint Bone Spine 2011;78:175. [2] Jacobsen S. Clin Rheumatol 2004;23:121. Disclosure of Interests Eleftheria Pertsinidou: None declared, Lars Klareskog Grant/research support from: Yes, but not for the presented study., Lars Alfredsson: None declared, Linda Mathsson Employee of: employed by Thermo Fisher Scientific, Monika Hansson: None declared, Helga Westerlind: None declared, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Saedis Saevarsdottir Employee of: Part-time employee at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project., Johan Ronnelid: none declared

Career situation of first and presenting author Young investigator. Introduction Separate studies have previously observed an association between exposure to physical workload (PW) and risk of developing rheumatoid arthritis (RA). Levels of antibodies against collagen type II (CII), which are associated with HLA-DRB*01 and *03 are transiently elevated at the time of RA diagnosis. PW might impose mechanical stress on the articular cartilage where CII is the main constituent, leading to immune activation and production of anti-CII antibodies. Objectives We hypothesize that exposure to PW would associate more strongly with anti-CII positive RA than with anti-CII negative RA. Methods Data involving 2916 incident RA cases and 5130 controls from the Swedish Epidemiological Investigations in Rheumatoid Arthritis (EIRA) population-based case-control study were analysed. Information on exposure to PW was collected through questionnaires. The odds ratios (OR) with 95% CI of developing anti-CII positive RA or anti-CII negative RA was calculated using logistic regression. Results The OR observed for the association between different types of PW and anti-CII positive RA ranged from 1.2 (0.8–1.8) to 1.7 (1.5–3.1). The OR for the association between PW and anti-CII negative RA ranged from 1.3 (1.1–1.4) to 1.6 (1.4–1.8). No statistically significant difference was observed between the OR for anti-CII positive RA and anti-CII negative RA (all p-values>0.10). Moreover, stratification for HLA-DRB*01 and *03 did not yield any statistical differences. Conclusions We found no evidence suggesting an association between PW and elevated anti-CII levels at the time of diagnosis. Acknowledgements We thank the investigators and participants from the EIRA study. The authors also thank Marie-Louise Serra and Lena Nise for data collection. Disclosure of Interest None declared.

Background:Antiphospholipid antibodies (aPL) of IgA isotype are prevalent in SLE patients of African-American, Afro-Caribbean and South-African origin, but data from North Africa are lackingObjectives:To compare and determine clinical significance of aPL isotypes in Sudanese and Swedish SLE patients using nation-based cutoffsMethods:Consecutive Sudanese (n=115) and Swedish (n=340) SLE patients and 106 and 318 age- and sex-matched national controls were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M anti-cardiolipin and anti-β2GPI were analyzed with two independent assays (Fluorescence Enzyme Immuno Assay (FEIA) from Thermo Fisher Scientific and Particle-based Multi-Analyte Technology (PMAT) from Inova Diagnostics). IgA anti-β2GPI domain1 (D1) was investigated with chemiluminescence (CIA), Inova Diagnostics. APS-related events were obtained from patients’ records. Manufacturers’, 95thand 99thpercentile cutoffs, based on national controls calculated by non-parametric methods, were usedResults:Sudanese patients had higher levels and prevalence of IgA aPL using manufacturers’ cutoffs (Table 1 and Figure 1). IgA/IgG aPL were also higher among Sudanese controls, But, Swedish patients were more often positive for IgA anti-β2GPI with both assays when national cutoffs were applied (Table 1). Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and no aPL, including IgA anti-β2GPI associated with thrombosis in Sudanese patients. Thrombosis in Swedes associated with IgG/IgM aPL. Fetal loss associated with aPL in both cohorts most evident after national adjustmentsTable 1.FEIASudann=92FEIASweden n=291PPMAT/CIASudann=93PMAT/CIASweden n=333PIgA CL median/IQR6.5/5.24.0/4.1194/185148/112IgG CL4.1/5.13.0/4.50.0002205/137190/215.10.09IgM CL2.7/6.83.7/5.40.02214/251.5193/35020.2IgA β2GPI6.3/14.22.7/3.8212/347118/152IgG β2GPI4.2/2.91.8/2.3158/110.7145.2/147.50.04IgM β2GPI2.0/3.01.4/2.20.006146.2/189.7132.5/235.40.09IgA B2GP1 D11542/1253.51683/1518.10.045IgA CL common cutoff n(%)9(9.8)17(5.8)0.232(35.2)75(22.7)0.02IgG CL4(4.3)21(6.7)0.414(15)72(22.1)0.1IgM CL3(3.2)14(4.5)0.610(11.4)43(13.1)0.6IgA β2GPI32(34.8)43(14.9)38(41.8)76(23)0.0004IgG β2GPI10(10.9)44(14.1)0.45(5.4)50(15.3)0.01IgM β2GPI10(10.9)27(8.7)0.512(13.6)42(12.9)0.8IgA B2GP1 D16(6.4)38(11.4)0.2IgA CL 95thcutoffn(%)9(9.8)54(18.6)0.04736(39.6)121(26.6)0.6IgG CL8(8.7)42(13.5)0.224(25.8)103(31.6)0.3IgM CL8(8.7)39(12.5)0.316(18.2)47(14.4)0.4IgA β2GPI18(19.6)100(34.7)0.00620(22)125(37.8)0.005IgG β2GPI2(2.1)67(21.5)19(20.4)83(25.5)0.3IgM β2GPI14(15.22)57(18.3)0.520(22.7)57(17.5)0.3IgA B2GP1 D125(26.9)69(20.7)0.2Figure 1.Conclusion:IgA anti-β2GPI levels were generally higher among Sudanese compared to Swedish SLE patients and controls, but after national adjustments more Swedish than Sudanese patients were positive. IgA anti-D1 was not increased in Sudanese patients. Previous studies on populations of African-origin, which demonstrate high prevalence of IgA aPL positivity, should be re-evaluated using similar cutoff approachAcknowledgments: :We thank Maryam Poorafshar at Thermo Fischer Scientific and Silvia Casas and Michael Mahler at Inova Diagnostics for help with analysesDisclosure of Interests:None declared