The Relationship between the complement system and subclinical carotid atherosclerosis in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) events and CV mortality. Subclinical carotid atherosclerosis is independently associated with rates of incident CV events among patients with RA. The complement system has been related to both the etiopathogenesis of RA and CV disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and carotid intima media thickness and carotid plaque in patients with RA. METHODS: 430 patients with RA were recruited. Functional assays of the three pathways of the complement system, utilizing new-generation techniques, were assessed. Additionally, serum levels of individual components of the complement system belonging to the three pathways were measured: C1q (classical), lectin (lectin), C2, C4, and C4b (classical and lectin), factor D and properdin (alternative), C3 and C3a (common), C5, C5a, and C9 (terminal), as well as regulators factor I and C1-inhibitor. Subclinical carotid atherosclerosis was evaluated by ultrasonography. Multivariable linear regression analysis was conducted to investigate the association between the complement system and carotid intima media thickness and carotid plaque. RESULTS: After multivariable adjustment, which included traditional CV risk factors and disease-related data, C3a and C5a exhibited significant positive correlations with carotid intima media thickness. Additionally, higher values of C1-inhibitor, properdin, C3, C5, and C5a were independently associated with the presence of carotid plaque. CONCLUSION: The complement system and subclinical carotid atherosclerosis are linked in patients with RA.

Relationship of Hematological Profiles with the Serum Complement System in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes.

Red blood cell distribution width as a surrogate biomarker of damage and disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: Red blood cell distribution width (RDW) is a measure of variability in mean corpuscular volume. Alterations in RDW can be observed in a variety of human disorders, including inflammatory, cardiovascular, and hepatic or renal diseases. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect virtually any organ in the body. In this work, our objective was to analyse how a complete characterisation of disease characteristics in a large series of patients with SLE is related to RDW values. METHODS: 284 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood count including RDW was assessed. Multivariable analysis was performed to analyse the relationship between RDW and SLE disease characteristics, including composite scores of disease activity and damage. RESULTS: After multivariable adjustment, RDW was higher in patients with SLE compared to controls (beta coefficient 0.8 [95% confidence interval: 0.3-1] %, p=0.003). Several disease characteristics, such as the presence of extractable nuclear antibodies and antiphospholipid syndrome, and the use of prednisone and azathioprine, were significantly associated with higher levels of RDW after adjustment for confounders. Of note, cumulative disease damage and disease activity scores were associated with higher RDW values after controlling for covariates. CONCLUSIONS: RDW may serve as a surrogate biomarker of accrual disease damage and activity in patients with SLE.

Mean Platelet Volume Is Related to Cumulative Disease Damage in Patients with Systemic Lupus Erythematosus.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 [95% confidence interval, -1.1 to -0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.

Amylin serum levels are upregulated in patients with systemic lupus erythematosus.

OBJECTIVES: Amylin is a pancreatic hormone that participates in glucose homeostasis. We aimed to investigate how serum amylin levels are expressed in patients with systemic lupus erythematosus (SLE) compared to matched controls, and their possible relationship to disease-related characteristics, such as activity or damage. METHODS: 144 SLE patients and 96 non-diabetic sex- (female 96% vs. 91%, p=0.43) and age-matched controls (49±11 vs. 51±8 years, p=0.09) were included. Amylin, insulin and C-peptide serum levels, as well as insulin resistance indexes were assessed in both groups. Multivariable regression analysis was performed to compare amylin between groups and to explore its interrelations with SLE features. The analyses were adjusted for glucocorticoids intake and for insulin resistance classic risk factors. RESULTS: Patients with SLE exhibited significant higher serum levels of amylin when compared to controls after multivariable analysis (beta coef. 1.56 [95%CI 1.01-2.11], p=0.000). Moreover, SLE patients not on prednisone (beat coef. 1.54 [95%CI 0.98-2.10] ng/ml, p=0.000) and those on prednisone (beta coef. 1.51 [95%CI 0.96-2.07] ng/ml, p=0.000) disclosed higher amylin serum levels compared to controls in the fully multivariable analysis. Hyperamylinaemia in SLE patients remained significant even adjusting for differences in the insulin resistance and beta cell production rates between patients and controls. The damage produced by the disease and its severity were independently and positively associated with amylin serum levels. CONCLUSIOINS: Amylin is upregulated in SLE patients compared to controls, regardless of the insulin resistance that SLE may present. The damage produced by the disease and its severity independently explains this upregulation.

Baseline Levels of Vitamin D in a Healthy Population from a Region with High Solar Irradiation.

The use of vitamin D (VitD) supplements has become widespread in the last decade due not only to the dissociation between the blood levels recommended as "optimal" and those shown by the healthy population but also to its presumed beneficial effects on multiple disorders. This work evaluated the levels of 25-hydroxyvitamin D (25(OH)D) in a healthy population of European origin living in a region with high solar irradiation. In serum samples from a population-based study conducted in the Canary Islands, levels of 25(OH)D were analyzed. In 876 individuals who had no history of kidney or malabsorption disorders and, who had not been treated with calcium and/or VitD supplementation, the median 25(OH)D level was 26.3 (5th; 95th percentile, 14.3; 45.8) ng/mL. Notably, 65.4% of the population had 25(OH)D blood levels below 30 ng/mL, 23.4% below 20 ng/mL and 6.4% below 15 ng/mL. Based on the lack of evidence supporting causality between 25(OH)D levels below what is recommended as optimal (≥20 ng/mL, or even ≥30 ng/mL) and major skeletal and non-skeletal diseases, and in light of the distribution of the concentration of this vitamin in healthy adults living under optimal conditions of solar irradiation, it seems reasonable to consider 25(OH)D levels below 20 ng/mL and close to 15 ng/mL as adequate for the general population.

Association of Gender, Diagnosis, and Obesity With Retention Rate of Secukinumab in Spondyloarthropathies: Results Form a Multicenter Real-World Study.

Background: Secukinumab has been shown effective for psoriatic arthritis (PsA) and axial spondylarthritis (AxSpA) in randomized trials. The aim of this study was to analyze baseline patient and disease characteristics associated with a better retention rate of secukinumab under real-world conditions. Patients and Methods: Real-life, prospective multicenter observational study involving 138 patients, 61 PsA and 77 AxSpA, who were analyzed at baseline, 6, 12 months and subsequently every year after starting secukinumab regardless of the line of treatment. Demographics and disease characteristics, measures of activity, secukinumab use, and adverse events were collected. Drug survival was analyzed using Kaplan-Meier curves and factors associated with discontinuation were evaluated using Cox regression. The machine-learning J48 decision tree classifier was also applied. Results: During the 1st year of treatment, 75% of patients persisted with secukinumab, but accrued 71% (n = 32) in total losses (n = 45). The backward stepwise (Wald) method selected diagnosis, obesity, and gender as relevant variables, the latter when analyzing the interactions. At 1 year of follow-up, the Cox model showed the best retention rate in the groups of AxSpa women (95%, 95% CI 93-97%) and PsA men (89%, 95% CI 84-93%), with the worst retention in PsA women (66%, 95% CI 54-79%). The J48 predicted secukinumab retention with an accuracy of 77.2%. No unexpected safety issues were observed. Conclusions: Secukinumab shows the best retention rate at 1 year of treatment in AxSpA women and in PsA men, independently of factors such as the time of disease evolution, the line of treatment or the initial dose of the drug.