The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher (p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. ...

Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or "autoimmunodeficiency" could be the reason for disorders.

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

In mid-2021, the SARS-CoV-2 (Severe Acute Respiratory coronavirus 2) infection, which caused the coronavirus disease (COVID-19) pandemic, affected more than 157 million people in all regions of the world and led to more than 3.2 million deaths. It is assumed that elderly age, uncontrolled inflammation, anti-inflammatory therapy, comorbid pathology, genetic and other factors can potentially lead to an increase in “sensitivity” to viral and bacterial infections, including SARS-CoV-2. The new version of the recommendations of the Association of Rheumatologists of Russia formulates the main provisions concerning the tactics of managing patients with Immune-mediated Rheumatic Diseases during the ongoing COVID-19 pandemic.

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Coronavirus disease 2019 (COVID-19) and immune-mediated rheumatic diseases. Recommendations of the association of rheumatologists of Russia

Aim The aim of this review was to summarize current knowledge about the scientific findings and potential clinical utility of heart rate variability measures in patients with systemic lupus erythematosus. Methods PubMed, Embase and Scopus databases were searched for the terms associated with systemic lupus erythematosus and heart rate variability, including controlled vocabulary, when appropriate. Articles published in English and available in full text were considered. Finally, 11 publications were selected, according to the systematic review protocol and were analyzed. Results In general, heart rate variability, measured in the time and frequency domains, was reported to be decreased in patients with systemic lupus erythematosus compared with controls. In some systemic lupus erythematosus studies, heart rate variability was found to correlate with inflammatory markers and albumin levels. A novel heart rate variability measure, heart rate turbulence onset, was shown to be increased, while heart rate turbulence slope was decreased in systemic lupus erythematosus patients. Reports of associations of changes in heart rate variability parameters with increasing systemic lupus erythematosus activity were inconsistent, showing decreasing heart rate variability or no relationship. However, the low/high frequency ratio was, in some studies, reported to increase with increasing disease activity or to be inversely correlated with albumin levels. Conclusions Patients with systemic lupus erythematosus have abnormal heart rate variability, which reflects cardiac autonomic dysfunction and may be related to inflammatory cytokines but not necessarily to disease activity. Thus measurement of heart rate variability could be a useful clinical tool for monitoring autonomic dysfunction in systemic lupus erythematosus, and may potentially provide prognostic information.

Heart rate variability in patients with systemic lupus erythematosus: a systematic review and methodological considerations.

Psoriasis is a chronic inflammatory process associated with an increased risk of cardiovascular risk factors. sCD40L has been suggested to have a possible role in the pathogenesis, of psoriasis and is known to be associated with inflammation, atherogenesis and cardiovascular events. This study investigated cardiovascular risk factors (sCD40L and homocysteine) as well as subclinical atherosclerosis indicators in psoriatic patients and control subjects. The study included 56 consecutive patients with chronic plaque-type psoriasis and 53 age and gender matched healthy controls admitted to a university hospital. Serum sCD40L and homocysteine levels were measured by ELISA. Carotid artery intima-media thickness and brachial artery flow mediated dilatation (FMD) measurements were determined ultrasonographically. Subjects who had a history of cardiovascular diseases and cardiovascular risk factors and receiving any systemic treatment were excluded from the study. Plasma sCD40L levels were significantly higher in psoriasis patients compared with healthy controls (1.33 ± 0.72 vs. 0.98 ± 0.70 ng/ml P = 0.012), whereas plasma homocysteine levels did not differ significantly between the two groups. FMD was significantly reduced in the psoriasis group compared to the controls (3.83 ± 5.03 vs. 8.45 ± 7.27% P = 0.0001). Multiple linear regression analyses indicated a significant association between psoriasis, sCD40L, and FMD. Psoriatic patients had higher sCD40L levels than healthy controls, which may lead to an increase in cardiovascular diseases. sCD40L may be a more reliable and early predictive marker of cardiovascular events in psoriatic patients. New treatment options that will be developed over sCD40L will benefit in prevention of psoriasis and its cardiovascular comorbidities.

Evaluation of serum sCD40L and homocysteine levels with subclinical atherosclerosis indicators in patients with psoriasis: a pilot study.

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-nonspecific autoantibodies to various components of the cell nucleus and cytoplasm and the development of immune-inflammatory damage to internal organs. The debut of SLE is preceded by an asymptomatic period, characterized by impaired immunological tolerance to its own autoantigens, determined by the multifaceted interaction of external, genetic and epigenetic factors, hormonal disorders, microbiome pathology, stress effects, etc. Development of a certain spectrum of clinical symptoms characteristic of SLE along with the detection of a reflects the progression of the immunopathological process in SLE, however, there is no generally accepted term that defines the patient’s condition, which has individual serological and clinical signs characteristic of this disease. In rheumatology, the concept of «incomplete» SLE is currently most often used. The problems of early diagnosis of SLE, clinical and laboratory predictors of the transformation of “incomplete” SLE into “reliable” SLE, difficulties in diagnosing SLE during the COVID-19 pandemic are considered. Particular attention is paid to the comparative characteristics of the immunopathological mechanisms of SLE and COVID-19.

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Problems of early diagnosis of systemic lupus erythematosus during the COVID-19 pandemic

Compared with general population, women suffering from systemic lupus erythematosus (SLE) have signs of coronary artery disease (CAD) five to eight times more often, especially in young age. Early development of atherosclerosis in patients with SLE is caused by conventional cardiovascular risk factors and specific ones, associated with the disease and its therapy. A slight increase in such an inflammatory marker as C-reactive protein (CRP) is thought to reflect the presence of subclinical inflammation in the vascular wall, connected with atherosclerotic process. The authors analyzed the frequency of clinical and subclinical (an increase in the thickness of intima-media complex (IMC)) atherosclerotic manifestations, the summary coronary risk, the prevalence of conventional risk factors, and CRP level in 133 female patients with SLE and in 50 healthy donors. Compared to the control group, SLE patients were younger, developed cardiovascular diseases (CAD, stenocardia, myocardial infarction, and cerebral stroke (p = 0.05) as well as arterial hypertension more often, had higher levels of hs-CRP and triglycerides, and lower levels of high density lipoprotein cholesterol (HDLC). There was a positive correlation between hs-CRP level and the activity of the disease according to ECLAM score, ES value, IgG and IgM levels, hematological disturbances (anemia, leucopenia, and/or thrombocytopenia) , and a negative correlation with total cholesterol level, HDLC there was a moderate correlation between hs-CRP and a maximal IMC value.

[The significance of cardiovascular risk factors and C-reactive protein to the development of atherosclerosis in women with systemic lupus erythematosus].

Aim. To evaluate clinical implications of pCD40L as a marker of atherosclerotic vascular affection in systemic lupus erythematosus (SLE). Material and methods. The examination of 132 females (mean age 35 years, SLE duration 96 months) assessed classic factors of atherosclerosis risk (AR), total coronary risk (TCR), detected subclinical atherosclerosis with ultrasonic scanning of the carotid arteries. Serum level of pCD40L was measured with enzyme immunoassay (EIA). Results. Concentration of pCD40L in SLE patients was higher than in the control group (7.1 ± .9 and 5.8 ± 3.1 ng/ml, respectively) but the difference was insignificant (p>0.05). Upper limit of normal value (M + 2SD) for pCD40L was 12 ng/ml. Elevation of pCD40L level was seen in 21% of SLE patients. Clinical manifestations of atherosclerosis risk were seen in 13% SLE patients, subclinical in 19 and 17% (increased intima-media thickness and atherosclerotic plaques, respectively). No correlations were found between pCD40L level and atherosclerotic symptoms. The pCD40L level was higher in SLE patients with the plaques than in those without them (p = 0.005). A positive correlation exists between a pCD40L concentration and maximal intima-media thickness (r = 0.2; p = 0.02), total cholersterol (r = 0.3; p = 0.002), LDLP cholesterol (r = 0.3; p=0.004), LDLP cholesterol (r = 0.2; p = 0.04) and age of the patients (r = 0.2; p = 0.03). In patients with TCR > 20% a pCD40L was significantly higher than in patients with TCR < 20% (p = 0.01). Conclusion. Elevated pCD40L level is a marker of atherosclerotic affection of the vessels, has an important clinical role for predicting risk of cardiovascular diseases in SLE and elicidation of the role of activation of cell immunity in development of atherosclerosis in this disease.

[Soluble CD40 ligand in systemic lupus erythematosus: link with atherosclerotic vascular affection].

Background Patients with Rheumatoid Arthritis (RA) have an increased risk for cardiovascular disease (CVD). Objectives To evaluate CVD prevalence and RA-related factors in RA patients participating in the prospective longitudinal (7 years duration) observational study. After the initial baseline visit, data will be collected every 6 months using the physician and patient questionnaires. Methods We studied 200 patients in a cross-sectional fashion: 165 (82,5%) females and 35 (17,5%) males, median (Me) age 55 [interquartile range (IR) 46;61] years who meet the 1987 ARA revised criteria for the classification of RA and enrolled in our cohort. Exclusion criteria: age less than 18 years or greater than 85 years at the time of enrollment into the registry, ACR functional class 4 RA. We considered the CVD (cardiovascular heart disease, cardiovascular revascularization procedure, myocardial infarction and stroke), traditional cardiovascular risk factors (smoking, family history of CVD, hypertension, dyslipidemia, menopausal status, body mass index (BMI), diabetes mellitus) and RA-related factors (duration of RA, disease activity score (DAS 28), seropositivity for IgM rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACCP), ACR functional class, treatment including both biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs) and steroids). Results The median disease duration of RA was 5 [1;10] years, early RA (≤ 1 year) was diagnosed in 60/200 (30%) patients, DAS 28 score was 3,9 [3,1;4,9], seropositive for IgM RF – 166/200 (83%) and/or ACCP – 151/200 (75,5%), 133/188 (73%) patients had erosions, ACR functional class I RA was 46/200 (23%), II RA – 129/200 (64,5), III RA – 25/200 (12,5%). Therapy: 87/200 (43,5%) patients received oral glucocorticoids, 141/200 (70,5%) – methotrexate, 18/200 (9%) – leflunomide, 6/200 (3%) – hydroxychloroquine, 2/200 (1%) – azathioprine, 43/200 (21,5%) - biologic DMARDs: rituximab – 13/200 (6,5%), adalimumab – 12/200 (6%), abatacept – 9/200 (6%), certolizumab pegol – 4/200 (2%), infliximab – 3/200 (1,5%), tocilizumab – 2/200 (1%). Ischemic heart disease was diagnosed in 38/200 (19%) patients, myocardial infarction – 3/200 (1,5%), cardiovascular revascularization procedure (coronary artery bypass graft) – 7/200 (3,5%), and stroke – 1/200 (0,5%). We observed the following frequency of traditional CVD risk factors: CVD family history – 58/200 (29%), dyslipidemia – 91/200 (46 %), BMI≥25 – 117/200 (58,5%), hypertension – 120/200 (60%), diabetes mellitus – 14/200 (7%), smoking status (ex-smoker+smoker) – 88/200 (44%), menopause – 110/165 (55%). Conclusions RA patients had a high frequency of CVD (20%). Ongoing observation of this cohort will further assess to assess the impact of chronic inflammation and specific therapy on CVD. Disclosure of Interest None Declared

https://ard.bmj.com/content/annrheumdis/72/Suppl_3/A865.3.full.pdf

AB0259 Characteristics and cardiovascular comorbidities in patients with rheumatoid arthritis in a local patient cohort in russia

Background Our aim was to compare serum levels of cytokines in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Objectives Comparative data on cytokine profile in SLE and rheumatoid arthritis RA patients are scarce. Methods We examined serum samples from 80 pts with SLE, median and interquartile range (25th–75th percentile) of disease duration 48 (2–432) months; age 31,5 (16–65) years; 72 female; 74 pts with RA, disease duration 90,0 (30,00–192,0) months; age 54,0 (44,0–62,0) years; 59 female, and 28 healthy donors. Cytokine analyses were performed with Bio-Plex® technology (Human Grp I Cytokine 27-plex panel). Results Pts with SLE had significantly lower levels of IL-1β, -1ra, -2, -9, eotaxin, G-CSF, IFN-γ, MIP-1β, TNF-α, VEGF and higher levels of IL-4, -6, -8, -12, GM-CSF, MCP-1, PDGF-BB, RANTES than healthy donors. Compared to RA, cytokine/chemokine levels from SLE were significantly different. The concentrations of IL-1β, -1ra, -2, -5, -6, -7, -9, -10, -13, 15, eotaxin, FGF, G-CSF, IFN-γ, IP-10, MIP-1α, TNF-α, VEGF in SLE were significantly lower than RA. The concentrations of IL-4, -8, MCP-1, MIP-1β, PDGF-BB, RANTES was higher in the SLE cohort (Table 1). Conclusions Serum concentration of most proinflammatory, Th-2 related, bone marrow–derived cytokines, stromal cells and angiogenic factors in SLE pts is substantially lower than in healthy donors and pts witch RA. These data demonstrate significantly higher chemokine levels in SLE versus RA. References Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007; 27(5):461–6. Kokkonen H, Soderstrom I, Rocklov J, Hallmans G, Lejon K, Rantapaa Dahlqvist S. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010; 62(2):383–91. doi: 10.1002/art.27186. Sieber J, Daridon C, Fleischer SJ, Fleischer V, Hiepe F, Alexander T, Heine G, Burmester GR, Fillatreau S, Dorner T. Active systemic lupus erythematosus is associated with a reduced cytokine production by B cells in response to TLR9 stimulation. Arthritis Res Ther. 2014;16(6):477. doi: 10.1186/s13075-014-0477-1. Disclosure of Interest None declared

https://ard.bmj.com/content/annrheumdis/75/Suppl_2/907.1.full.pdf

T.A. Panafidina

Papers

Problems of early diagnosis of systemic lupus erythematosus during the COVID-19 pandemic

[The significance of cardiovascular risk factors and C-reactive protein to the development of atherosclerosis in women with systemic lupus erythematosus].

[Soluble CD40 ligand in systemic lupus erythematosus: link with atherosclerotic vascular affection].

AB0259 Characteristics and cardiovascular comorbidities in patients with rheumatoid arthritis in a local patient cohort in russia

AB0030 Cytokine Profiles in Systemic Lupus Erythematosus and Rheumatoid Arthritis