Objective To investigate whether T-bet+ B cells, as well as age-associated B cells/ABCs (CD19 + CD21-CD11c + T-bet+) and double-negative B cells/DN (CD19 + IgD-CD27- CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans.Methods Flow cytometry was used for enumerating T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients. Whole blood assay cultures, combined with in vitro pharmacological treatments, were performed to evaluate the effects of hydroxychloroquine, anifrolumab, and fasudil (a ROCK kinase inhibitor) on T-bet+ B cells' percentage. Moreover, previously published single-cell RNA sequencing (scRNA-seq) data were used in a meta-analysis to allow characterization of genes and pathways associated with the biology of T-bet in B cells.Results T-bet+ B cells displayed an expansion in SLE patients [1.47 (1.9-0.7) vs 10.85 (37.4-3.6)]. Similarly, both ABCs and DN were found to be expanded. Interestingly, percentages of T-bet+ B cells positively correlated with patients' SLEDAI scores (rs = 0.55, P = 0.007). Cell culture experiments conducted revealed that all three agents tested can deplete T-bet + B cells (without affecting the cell viability of lymphocytes, T cells, and B cells). According to bioinformatics analyses, T-bet is highly expressed in two B-cell clusters with pathogenic characteristics for SLE (designated as atypical memory B cells and activated na & iuml;ve B cells). These clusters can be targeted for therapeutic interventions.Conclusions T-bet+ B cells can serve as a putative prognostic biomarker of lupus severity. Circumstantial data suggest that these cells may promote disease pathogenesis and may represent a novel therapeutic target. This paper investigates whether T-bet+ B cells, as well as age-associated B cells/ABCs (CD19+CD21-CD11c+T-bet+) and double-negative B cells/DN (CD19+IgD-CD27-CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans. Flow cytometry was used for enumerating T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients.

Objective This study aims to clarify whether T-bet+ B cells, as well as the sub-populations of age-associated B cells/ABCs (CD19+CD21-CD11c+T-bet+) and double-negative B cells/DN (CD19+IgD-CD27-CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans. Methods Flow cytometry was used to enumerate and immunophenotype T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients, in order to identify correlations between the cell populations and the clinical profiles of the subjects. Moreover, in order to evaluate the effects of traditional and modern pharmaceutical agents on T-bet+ B cells' percentage, 24h-long primary cell cultures combined with in vitro pharmacological treatments (of 1h) were performed. Various concentrations of hydroxychloroquine, anifrolumab and fasudil (a ROCK kinase inhibitor) have been tested. Last, data derived from previous published single-cell RNA sequencing (scRNA-seq) studies, regarding 6 healthy donors and 11 active SLE patients, were used for a meta-analysis focusing on T-bet+ B cells, so as to allow characterization of the genes and pathways associated with the biology of this specific transcription factor. Results T-bet+ B cells, as well as ABCs and DN, displayed a statistical significant expansion in the patients, compared to the healthy donors. Interestingly, percentages of T-bet+ B cells and DN B cells positively correlated with the SLEDAI scores of the patients. Cell culture experiments conducted, revealed that all three drugs tested are capable of depleting T-bet+ B cells (while leaving unaffected the total numbers of lymphocytes, T cells and B cells, respectively). According to bioinformatics analyses, moreover, T-bet in B cells seems to affiliate with transcription factors that play a role in germinal centers' development (such as BCL6 and IRF8) in lupus patients, while in healthy individuals it affiliates with JUN. Additionally, an analysis regarding intracellular communications amongst B cell populations revealed that the transcription factor of interest is closely associated with inflammatory secretome during lupus. Conclusions T-bet+ B cells associate with SLEDAI, thus can serve as a prognostic biomarker of lupus severity. Furthermore, these cells promote disease pathogenesis and can be targeted for therapeutic interventions. Acknowledgements The research work is supported by the Hellenic Foundation for Research and Innovation (HFRI) under the 3rd Call for HFRI PhD Fellowships (Fellowship Number: 5148, Awarded to AS). Moreover, the study is funded (partially) by the Hellenic Society of Rheumatology & Professional Association of Rheumatologists (Protocol Number: 1064, Research Grant awarded to CA)

The rates of relapses and therapy discontinuation in patients with giant cell arteritis (GCA) in the modern therapeutic era have not been defined. We aimed to evaluate the glucocorticoid (GC) discontinuation rate and the factors associated with relapses in a contemporary GCA cohort. Patient and treatment data were collected cross-sectionally at first evaluation and 2 years later (second evaluation), in a multicenter, prospective GCA cohort. Predictors of relapses were identified by logistic regression analyses. 243 patients with GCA were initially included (67% women, mean age at diagnosis: 72.1 years, median disease duration: 2 years) while 2 years later complete data for 160 patients were available and analyzed. All patients had received GCs at diagnosis (mean daily prednisolone dose: 40 mg) while during follow-up, 37% received non-biologic and 16% biologic agents, respectively. At second evaluation, 72% of patients were still on therapy (GCs: 58% and/or GC-sparing agents: 29%). Relapses occurred in 27% of patients during follow-up; by multivariable logistic regression analysis, large vessel involvement at diagnosis [odds ratio (OR) = 4.22], a cardiovascular event during follow-up (OR = 4.60) and a higher initial GC daily dose (OR = 1.04), were associated with these relapses. In this large, real-life, contemporary GCA cohort, the rates of GC discontinuation and relapses were 40% and 27%, respectively. Large vessel involvement, a higher GC dose at diagnosis and new cardiovascular events during follow-up were associated with relapses.

Background: There are limited data regarding therapy discontinuation in patients with giant cell arteritis (GCA) followed for a long period of time (>5 years). Objectives: We aimed to evaluate the long-term rate and factors associated with therapy discontinuation in a real-life GCA cohort. Methods: Patient and treatment data were collected at 3 different time points (baseline, 2 and 5 years later) in a multicenter, prospective GCA cohort. The rates of therapy discontinuation and its predictors were identified by uni- and multi- variable logistic regression analyses Results: 89 patients with data available for all time points of evaluation were included in the study; 75% were women with a mean age of 71.6±8.1 years and a median disease duration from diagnosis to last evaluation of 7.2 years. All patients had been treated initially with glucocorticoids (GCs, 100%, median daily dose: 40mg prednisolone) while during follow-up, 34% (30/89) had received cs-DMARDs and/or b-DMARDs (17%, 15/89), respectively. 40.4% (36/89) of patients had ≥1 disease relapses during this period. At the last follow-up visit, 48% (43/89) of patients managed to discontinue all therapies and 54% GCs (48/89), respectively. By uni-variable logistic regression analysis, factors associated with therapy discontinuation included the absence of relapses (OR=2.76; 95%CI: 1.13-6.74) and the lack of treatment with GC-sparing agents (b- and/or cs-DMARDs, OR=4.69; 95%CI: 1.76-12.50). By multi-variable logistic regression analysis, patients who did not require a GC-sparing agent (b- and/or cs-DMARDs) had a higher likelihood to discontinue all therapies (OR=5.15; 95%CI: 1.56.-17.01). Conclusion: In this real-life GCA cohort, approximately 40% of patients relapsed while only half were able to discontinue all therapies, ~7 years after diagnosis. The absence of relapses and requirement for GC-sparing agents were associated with a higher likelihood of drug discontinuation. Whether earlier introduction of GC-sparing agents could improve the chance for drug discontinuation by preventing relapses remains to be studied. REFERENCES: NIL. Acknowledgements: Supported in part by the Greek Rheumatology Society and Professional Association of Rheumatologists (ERE-EPERE) and the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece (DV #12085, 12086). Disclosure of Interests: None declared.

Apart from serving as a Th1 lineage commitment regulator, transcription factor T-bet is also expressed in other immune cell types and thus orchestrates their functions. In case of B cells, more specifically, T-bet is responsible for their isotype switching to specific IgG sub-classes (IgG2a/c in mice and IgG1/3 in humans). In various autoimmune disorders, such as systemic lupus erythematosus and/or rheumatoid arthritis, subsets of T-bet expressing B cells, known as age-associated B cells (CD19+CD11c+CD21-T-bet+) and/or double-negative B cells (CD19+IgD-CD27-T-bet+), display an expansion and seem to drive disease pathogenesis. According to data, mostly derived from mice models of autoimmunity, the targeting of these specific B-cell populations is capable of ameliorating the general health status of the autoimmune subjects. Here, in this review article, we present a variety of therapeutic approaches for both mice and humans, suffering from an autoimmune disease, and we discuss the effects of each approach on T-bet+ B cells. In general, we highlight the importance of specifically targeting T-bet+ B cells for therapeutic interventions in autoimmunity. Targeting of ABCs/DN, in mice models of autoimmunity and/or humans suffering from autoimmune disorders, leads to diminished levels of T-bet expression in B cells and thus improves the general health status of the subjects. Graphical Abstract

Background: Age-associated B cells (ABCs) constitute a B cell subset, defined as CD19+CD21- CD11c+, that expands continuously with age and accumulates strongly in individuals with autoimmune and/or infectious diseases. In humans, ABCs are principally IgD-CD27- double-negative (DN) B cells. Data from murine models of autoimmunity, implicate ABCs/DN in the development of autoimmune disorders. T-bet, a transcription factor which is highly expressed in these cells, is considered to play a major role in various aspects of autoimmunity, such as the production of autoantibodies and the formation of spontaneous germinal centres. Aims of the study: Despite the available data, the functional features of ABCs/DN and their exact role in the pathogenesis of autoimmunity remain elusive. This project focuses on the investigation of the role of ABCs/DN in the pathogenesis of systemic lupus erythematosus (SLE) in humans, as well as the effects that various pharmacological agents may have on these cells. Methods: Samples from patients with active SLE will be used to enumerate and immunophenotype- via flow cytometry- the ABCs/DN found in the peripheral blood of the patients. Transcriptomic analysis and functional assays for the cells, both before and after in vitro pharmacological treatments, will also be performed. Anticipated benefits: The results of the study are expected to allow characterization of the pathogenetic role of ABCs/DN in SLE and could probably contribute, following careful association with the clinical state of the patients, towards the discovery and validation of novel prognostic and diagnostic markers of disease.

Background Childhood-onset Systemic Lupus Erythematosus (cSLE) is a rare autoimmune disease with multi-system manifestations, more severe disease course and higher frequency of morbidity than adult-onset SLE. Belimumab is the first treatment for cSLE approved for children ≥5 years of age. Objectives To investigate the efficacy and safety of Belimumab in adult patients with cSLE. Methods A prospective observational (non-interventional) study, involving adult patients with cSLE was conducted. During the 9-yearstudy period (01/2015 to 12/2022), adults with a cSLE diagnosis and Belimumab receivers (by intravenous or subcutaneous administration) for >12 consecutive months were enrolled. All patients met the revised 1997 American College of Rheumatology (ACR) or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and were followed at regular intervals (up to 6 months) in the Transition Rheumatology Outpatient Clinic. SLE activity was defined according to SLEDAI-2K and the SELENA-SLEDAI Physician Global Assessment (PGA), scale 0–3 [1]. At the last follow-up visit, response to therapy was assessed by Lupus Low Disease Activity State (LLDAS), remission state and SLE Responder Index (SRI4). LLDAS was defined as: i) SLEDAI-2K ≤4, with no activity in major systems ii) no new lupus disease activity compared to previous evaluation iii) a SELENA-SLEDAI PGA ≤1 iv) current prednisolone (or equivalent) dose ≤7.5 mg daily and v) standard maintenance doses of immunosuppressive drugs. [2]. Remission was defined as i) clinical SLEDAI-2K=0 ii) dose of prednisone ≤5 mg/day according to the DORIS definition [3]. SRI4 was defined as i) ≥4-point reduction from baseline in SELENA-SLEDAI score, ii) no worsening in PGA and iii) no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline [4]. Results A total of 15 patients (14 females) were enrolled in the study. At baseline, the patients’ current mean (SD) age was 25.4 (7) years and the interval from disease onset to first Belimumab administration 12.4 (7.3) years. Half of the patients had a history of lupus nephritis and 42.8% were aPL positive. All patients were under hydroxychloroquine treatment and 80% of them were additionally receiving a second immunosuppressive agent (Methotrexate, MMF, Azathioprine). Glucocorticoids (GCs) were concomitantly administered in 13 (86.6%) patients in a dose of ≥7.5mg in 57.1% of them. The patients’ SLEDAI-2K mean (SD) score before Belimumab initiation was 12.1 (2.3), indicating high disease activity. The mean (SD) duration of Belimumab administration was 36.2 (1.9) months. At the last follow up visit, ongoing therapy with Belimumab was recorded in 66.7% of the cohort. SLEDAI-2K mean (SD) score was reduced to 3.5 (2.3), 1 patient (6.6 %) was in remission, 9 (60%) patients had mild and none high disease activity. The majority (78.5%) met the LLDAS definition and 78.5% were SRI4 Responders. Half of the patients (53.8%) achieved lower doses or discontinuation of GCs and 26.7% accomplished a reduction of the immunosuppressant’s dose. Reasons for Belimumab discontinuation included pregnancy issues, infection and low adherence (3, 1, 1 patient respectively). None of the patients experienced a serious adverse event. Conclusion In this cohort of adult patients with cSLE, Belimumab was well-tolerated and effectively reduced disease activity allowing the downstream of GCs’s dose. References [1]MOSCA M, BOMBARDIERI S: Assessing remission in systemic lupus erythematosus. Clin Exp Rheumatol. 2006;24:99-104. [2]FRANKLYN K, et al: Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016;75:1615-21. [3]VAN VOLLENHOVEN R et al: A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2017;76:554-61. [4]KMA C Luijten et al: The systemic Lupus Erythematosus Responder Index (SRI); a new SLE disease activity assessment. Autoimmun Rev 2012;11:326-9 Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Rheumatoid Arthritis (RA) is characterized by increased risk for cardiovascular disease [1]. Microvascular dysfunction often coexists with or even precedes macrovascular disease, possibly due to common mechanisms of vascular damage, such as inflammatory processes and oxidative stress [1, 2]. Objectives To investigate the correlation between microcirculatory changes and markers of atherosclerosis in patients with RA. Methods The study evaluated the structural capillaroscopic parameters using video-capillaroscopy (NVC). Applying the tonometry method, the augmentation index (Aix) was calculated, as well as its adjustment to a heart rate of 75 (Aix75). Additionally, pulse wave velocity (PWV), and mean intima-media thickness (cIMT) of the two common carotids, as well as central systolic and diastolic blood pressure (cSBP, cDBP), were calculated in each patient. Results A total of 32 patients with a mean age of 63.06±11.05 years were studied. At the same time, the existence of ramified capillaries was significantly correlated with PWV (r=0.38, p=0.032), while the existence of crossed capillaries was inversely correlated with cSBP (r=-0.43, p=0.014). Based on the measurements performed in each capillary, a significant correlation was found between the internal capillary diameter and cSBP (r=0.36, p=0.043). In 16 patients the subpapillary venous plexus was visible and this finding was significantly correlated with the mean value of left cIMT (p=0.005). Conclusion The findings of this small study indicate an association between NVC alterations and markers of atherosclerosis in patients with RA. References [1] Dijkshoorn B, Raadsen R, Nurmohamed MT. Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022. J. Clin. Med. 2022, 11, 2704. https://doi.org/10.3390/jcm11102704 [2] Bordy R, Totoson P, Prati C, Marie C, Wendling D, Demougeot C. Microvascular endothelial dysfunction in rheumatoid arthritis. Nat Rev Rheumatol. 2018 Jul;14(7):404-420. doi: 10.1038/s41584-018-0022-8 Acknowledgements: NIL. Disclosure of Interests None Declared.

Background Patients with pre-existing rheumatic diseases may be exacerbated during SARS-CoV-2 infection, or may develop new autoimmune features. Furthermore, immunosuppressive agents used to treat autoimmunity-inflammation as well as comorbidities can also affect the disease outcome. Objectives To evaluate the outcome of rheumatic diseases after Covid 19 infection in patients diagnosed with rheumatic diseases, under various immunosuppressive treatment, as well as the effects of vaccines against Covid or antiviral treatment in this sensitive population group. Methods During the pandemic, 1493 patients with autoimmune or autoinflammatory disease who were continuously followed up in two tertiaries hospitals in northern and northwestern Greece were included in the current study. The patients were compared with 769 controls after adjustment for age, sex, weight, vaccination status and comorbidities. Of the 1493 patients, 648 had rheumatoid arthritis, 282 psoriatic arthritis, 173 ankylosing spondylitis, 122 systemic lupus erythematosus, 98 Sjogren’s syndrome, 43 polymyalgia rheumatica, 34 mixed connective tissue disease or overlapping syndromes, 31 vasculitis, 27 systemic sclerosis, 18 myositis, 10 Behcet syndrome, 5 primary antiphospholipid syndrome and 2 had Familial Mediterranean Fever. The vast majority of patients and controls were fully vaccinated (82%) and 397 patients received antiviral treatment, 94% of them were fully vaccinated. Results Covid 19 disease in vaccinated patients with rheumatic diseases was shown to perform the same or about the same as those in the control group after adjustment for risk factors for severe disease. 19 of our patients required admission in the intensive care unit (62% full vaccinated) while a total of 12 died (66% non vaccinated). Major risk factors for severe disease were previous respiratory failure, chronic renal impairment, obesity, and failure to receive antiviral therapy. It was also shown that infection with Covid led to an exacerbation or induction of autoimmune disorders in 25 of the participants. Conclusion In this large cohort, Covid 19 disease was shown to affect patients with autoimmune rheumatic diseases the same or approximately the same way as the general population if they are fully vaccinated and if they start timely antiviral treatment where indicated. Further research and monitoring of the results after the multiple mutations of the virus is advisable. References None. Acknowledgements: NIL. Disclosure of Interests None Declared.

Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. To this end, we gathered a group of rheumatologists, nephrologists and a nephropathologist to review current evidence regarding diagnosis and management of LN. In this consensus paper, we summarize the key points from this meeting and provide practice guidelines for the management of kidney involvement in SLE, in view of emerging new data concerning novel agents approved recently. Renal biopsy is indispensable for the management of LN. Yet, important pearls and pitfalls need to be considered regarding indications and interpretation, which are summarized in informative tables. In new-onset LN, experts agreed that, although belimumab may be added from disease onset, patients with moderate to severe proliferative nephritis (defined as: NIH activity index > 5 plus ≥ 1 of the following: (i) NIH chronicity index > 2, (ii) proteinuria > 3 g/24 h, and (iii) increase in serum creatinine > 20%) may be more likely to benefit the most. In all other patients who have already started standard-of-care treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CY), belimumab could be considered in cases with an inadequate clinical response by 3 months, or in cases that experience a nephritic flare following initial response, or have an inability to reduce the dose of glucocorticoids. In all circumstances, the drug should be given as add-on therapy, that is, in combination with a standard-of-care therapy (MMF or CY). Voclosporin could be considered for up to 3 years, in combination with MMF, in patients with heavy proteinuria (well above the nephrotic range), wherein a quick reduction of protein loss in urine is desirable to avoid the complications of the nephrotic syndrome, either as part of the initial regimen, or in cases of inadequate reduction of proteinuria with MMF. In view of the potential scarring effects, long-term administration beyond the first year requires further documentation.

•Age-associated B cells (ABCs) are considered as drivers of autoimmune disease pathogenesis.•SWEF proteins (DEF6 and SWAP-70) regulate ABCs, via a mechanism involving IRF5 and IL-21.•Lack of DEF6 and/or SWAP-70 leads to increased Rho-kinase (ROCK) activity in immune cells.•ROCK inhibitors may deplete ABCs, thus contribute to autoimmune disease management and therapy.

Vascular injury eventually resulting in the establishment of cardiovascular disease is a serious complication in rheumatoid arthritis (RA). Nailfold videocapillaroscopy (NVC) is a non-invasive imaging modality that enables the quantitative and qualitative assessment of the peripheral microvasculature. Nevertheless, capillaroscopic patterns remain inadequately defined in RA, especially regarding their clinical significance as potential markers of systemic vascular impairment. Consecutive RA patients underwent NVC using a standardized protocol, to assess the following parameters: capillary density, avascular areas, capillary dimensions, microhemorrhages, subpapillary venous plexus, and presence of ramified, bushy, crossed and tortuous capillaries. Carotid-femoral pulse wave velocity (PWV) and pulse pressure were measured as well-acknowledged markers of large artery stiffening. The vast majority of our cohort (n = 44) presented a combination of non-specific and abnormal capillaroscopic parameters. Capillary ramification was associated with both PWV and pulse pressure, even after adjustment for cardiovascular risk factors and systemic inflammation. Our study highlights the high prevalence of a wide range of capillaroscopic deviations from the normal patterns in RA. Furthermore, it provides for the first time evidence of an association between structural disorders of the microcirculation and markers of macrovascular dysfunction, suggesting that NVC might have a role as an index of generalised vascular impairment in RA.

Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment’s efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was −0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline.

Introduction Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort. Materials and methods Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later. Results One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58–59.85), history of cancer (OR = 2.35, 95% CI: 1.09–5.06), bDMARD use (OR = 1.85, 95% CI: 1.29–2.65), seropositivity (OR = 1.47, 95% CI: 1.05–2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17–1.51). Male sex (OR = 0.65, 95% CI: 0.43–0.99) was a negative predictor for pneumococcal vaccination during follow-up. Discussion Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a “vaccination culture” in RA patients.

Objectives: This study will investigate olanzapine's cytogenetic behavior in cultured human T lymphocytes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: Three olanzapine solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides and stained with the fluorescence plus Giemsa method. Sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope. Results: There was a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE and RA patients compared to healthy individuals and a statistically significant (p=0.001) reduction of PRI and MI in the highest concentration in the SLE group. Moreover, Spearman's rank correlation coefficient was applied to calculate the correlation between SCEs, PRI, and MI. Negative significant correlations were noticed for both patient groups concerning SCEs-PRI alterations and SCEs-MI alterations. Conversely, positive correlations were noticed for both patient groups for PRI-MI alterations. Conclusions: Olanzapine affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures and DNA damage response. Considering the use of olanzapine in neuropsychiatric symptoms of SLE, further in vivo studies are necessary to evaluate its effect on human DNA.