Complete blood count-derived ratios have been described as inflammatory biomarkers in several diseases. These hematological scores include the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index ([SIRI]; neutrophils × monocytes/lymphocytes). Our aim was to study how these biomarkers are related to disease expression in a large and well-characterized series of patients with systemic lupus erythematosus (SLE). A total of 284 SLE patients and 181 age- and sex-matched healthy controls were recruited. The NLR, MLR, PLR, and SIRI were calculated, and activity (SLEDAI-2K), severity (Katz), and damage index (SLICC-DI) scores were assessed in patients with SLE. Multivariable linear regression analysis was performed to study whether these scores differ between patients and controls and how they are related to clinical and laboratory features of the disease. Crude cell counts of neutrophils, monocytes, lymphocytes, and platelets were lower in SLE patients compared to controls. Despite this, NLR, MLR, and PRL, but not SIRI, were higher in SLE patients than in controls after multivariable analysis. However, the relationship between the different scores and disease characteristics was limited. Only the Katz severity index revealed a significant positive relationship with SIRI, NLR, and MLR after adjustment for covariates. Similarly, alternative complement cascade activation and low C3 were significantly associated with higher NLR, MLR, and PLR. In conclusion, although cytopenias are a common feature of patients with SLE, hematologic composite scores are independently higher in this population compared to controls. However, the relationship of these scores with the characteristics of the disease is scarce, with the relationship with the complement system being the most consistent.

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.

The monocytes to high-density lipoprotein (HDL)-cholesterol ratio (MHR) indicates inflammation based on the anti-inflammatory properties of HDL-cholesterol as well as the pro-inflammatory effect of monocytes. Several studies have investigated MHR in various disorders, specifically in cardiovascular diseases. Consequently, MHR has been significantly associated with cardiovascular and all-cause mortality in the general population, regardless of established risk factors. However, its role in the augmented risk of cardiovascular disease found in rheumatoid arthritis (RA) has not been studied to date. This is a cross-sectional study that encompassed 430 patients with RA and 208 controls matched by sex and age. Complete blood cell count and complete lipid profile were evaluated. Multivariable analysis was made to analyze the relationship between MHR and RA disease and features subclinical carotid atherosclerosis, and traditional CV factors including insulin resistance and beta cell function indices. MHR values did not differ between controls and patients after multivariable adjustment (12 ± 6 vs. 11 ± 6, p = 0.18). No relationship between this ratio and the characteristics of the disease was found excluding ESR, which showed a significant and positive association with MHR after adjustment for covariates. MHR significantly correlated with Systematic Coronary Risk Evaluation-2 (SCORE2) cardiovascular risk algorithm, and insulin resistance and beta cell function parameters after adjustment. In conclusion, MHR does not differ between patients with RA and controls. The relationship of this biomarker with disease-related data is poor. However, MHR is highly and positively related to cardiovascular risk and insulin resistance in RA.

Transforming growth factor beta (TGF-β) is a highly pleiotropic cytokine that has broad anti-inflammatory and immunosuppressive effects. In patients with systemic lupus erythematosus (SLE), the immunosuppressive effect of TGF-β1 is thought to be dysfunctional. In the present work, we aimed to study the relationship between the serum levels of TGF-β1 with the characteristics of the disease as well as with the patterns of activity, damage, or severity of the disease. Two hundred and eighty-four patients with well-characterized SLE were recruited. The serum levels of TGF-β1 were assessed. A multivariable linear regression analysis was performed to analyze the relation of disease characteristics to TGF-β1. The Katz severity index (beta coefficient 179 [95% confidence interval 7–350] pg/mL, p = 0.041) and SLEDAI activity index (beta coefficient 96 [95% CI 20–171] pg/mL, p = 0.014) were associated with higher serum levels of TGF-β1 after the multivariable analysis. When the disease-specific features were studied, ocular and cardiovascular manifestations were positively associated with serum TGF-β1 levels. In contrast, gastrointestinal and musculoskeletal involvements were associated with lower levels of circulating TGF-β1. Among patients with SLE, the serum levels of TGF-β1 were highly associated with disease-related manifestations.

Malondialdehyde (MDA) is a marker of oxidative stress and antioxidant status. Oxidative stress has been observed to be increased in systemic lupus erythematosus (SLE). Some studies have shown that MDA is upregulated in SLE compared to controls. However, the literature lacks reports regarding the relationship of MDA to disease manifestations. This is relevant since SLE is a multisystemic disease which may affect virtually any organ in the body. In this study, we set out to analyze how MDA serum levels are associated with disease expression in a large series of SLE patients who were fully characterized in clinical and laboratory terms. A total of 284 patients with SLE were recruited. Serum levels of MDA, and the activity (SLEDAI), severity (Katz) and damage index (SLICC-DI) scores, full lipid profile, and carotid subclinical atherosclerosis were assessed. In addition, a full characterization of the complement system was performed in SLE patients’ samples. Multivariable linear regression analysis was executed to study the relationship between clinical and laboratory disease characteristics and MDA. A statistically significant negative relationship was found between disease duration and MDA. In contrast, the presence of anti-nucleosome antibodies was positively associated with MDA. Regarding the SLICC-DI areas, both the musculoskeletal domain and the cutaneous domain were significantly related to higher serum MDA values. Furthermore, after adjustment for confounding factors, lower levels of the classical complement pathway, which denotes activation, were associated with higher serum levels of MDA. In conclusion, cumulative musculoskeletal and skin damage in SLE patients is associated with superior serum levels of MDA. In addition, activation of the complement system is also related to higher circulating MDA levels.

Background: The Metabolic Score for Insulin Resistance (METS-IR) is a newly developed index that has been described to predict cardiovascular (CV) events. In this study, we calculated the METS-IR index in patients with rheumatoid arthritis (RA), a condition linked to an elevated CV risk. We then examined its relationship with disease characteristics and CV comorbidities, including disease activity, lipid profile, subclinical carotid atherosclerosis, and insulin resistance indices. Methods: A total of 515 RA patients were recruited. Disease-related characteristics and disease activity indices, including the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simple Disease Activity Index (SDAI) were calculated. Additionally, the complete lipid profile, insulin resistance indices, metabolic syndrome criteria, and carotid ultrasound for intima–media thickness and carotid plaque detection were assessed. METS-IR was calculated. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and METS-IR. Results: METS-IR was positively correlated with age, body mass index, and traditional cardiovascular risk factors such as metabolic syndrome and insulin resistance indices. Carotid intima–media thickness—but not the presence of carotid plaque—was associated with significantly higher METS-IR values. Regarding disease-related characteristics, C-reactive protein and disease activity indices demonstrated a significant positive association with METS-IR after multivariable adjustment. Specifically, C-reactive protein was associated with higher METS-IR values (beta coefficient 0.2, 95% CI: 0.1–0.3, p < 0.001). All disease activity indices, except CDAI, showed a significant positive relationship with METS-IR. Conclusions: METS-IR is linked not only to CV risk factors but also, independently, to inflammatory disease activity in patients with RA. Its association with CV events in the general population and disease activity in RA highlights the significant role of inflammation in driving excessive cardiovascular risk in RA. This underscores the intricate relationship between metabolic dysfunction, systemic inflammation, and CV outcomes in RA.