Search Results (67)

Background/Objectives: This study was conducted to analyze the associations between vascular endothelial growth factor (VEGF) serum concentrations and immunological biomarkers, inflammatory parameters, classical atherosclerosis risk factors, and cardiovascular manifestations in systemic lupus erythematosus (SLE) patients. Methods: The project included 83 individuals suffering from SLE, with 20 healthy individuals as controls. The serum levels of VEGF were determined through the ELISA method using R&D Systems tests. Laboratory markers, autoantibody profiles, traditional atherosclerotic risk factors, and organ manifestations were evaluated. Atherosclerotic changes were determined based on several indices including carotid intima-media thickness, ankle-brachial index and high resistance index assessments. Results: The reference range of serum VEGF concentrations was established based on the 25th and 75th percentiles obtained in the controls. High VEGF levels were significantly correlated with the presence of selected anti-phospholipid antibodies such as anti-prothrombin (OR = 10.7; 95%CI: 2.1–53.4) and anti-beta2 glycoprotein I (OR = 3.5; 95%CI: 1.1–10.8), as well as cardiac disorders (OR = 8.0; 95%CI: 1.6–39.5). On the other hand, low concentrations of VEGF were significantly related to lower frequencies of anti-double-stranded DNA antibodies (OR = 0.31; 95%CI: 0.11–0.91) and anti-endothelial cell antibodies (OR = 0.30; 95%CI: 0.11–0.85). Patients with low VEGF levels showed significantly reduced risks of atherosclerotic lesions (OR = 0.24; 95%CI: 0.04–0.99) and vasculitis development (OR = 0.17; 95%CI = 0.03–0.91). Conclusions: In conclusion, VEGF’s pathogenetic role in SLE and SLE-related atherothrombosis is manifested in close correlation with aPLs which may enhance their direct impact on endothelium. High VEGF levels are helpful for identifying cardiovascular risk in patients, while low concentrations indicate lower disease activity, as well as a lower risk of organ involvement. Full article

Background: Urticarial vasculitis (UV) is a rare form of small-vessel vasculitis characterized by persistent urticarial lesions and systemic manifestations. It differs from chronic spontaneous urticaria (CSU) both clinically and pathogenetically, often requiring systemic therapy. Despite its complexity, no standardized treatment algorithm exists. Methods: We conducted a retrospective, monocentric, observational study on 11 patients diagnosed with UV at the Dermatology Unit of Tor Vergata University Hospital (Rome) between 2014 and 2024. Demographic, clinical, serological, and therapeutic data were collected from medical records. The therapeutic response was assessed using the Urticaria Control Test (UCT) score. Results: The cohort comprised predominantly women (91%), with a mean age at diagnosis of 52.8 years. Autoimmune thyroiditis was the most frequent comorbidity (64%). Hypocomplementemia was detected in only one patient (9%), who also had systemic lupus erythematosus. Antihistamines, while usually prescribed, showed limited efficacy since none of the patients achieved complete remission with monotherapy. Systemic corticosteroids demonstrated rapid and effective control in acute phases. Omalizumab produced variable responses, with two patients achieving a high response (HR) and one reaching complete remission (CR). Methotrexate and cyclosporine yielded inconsistent outcomes. Due to the heterogeneity and limited sample size, statistical analyses were not performed. Conclusions: UV presents with diverse clinical profiles and therapeutic responses. No treatment proved universally efficacious, but corticosteroids and omalizumab were effective in an acute and maintenance phase, respectively. Our findings underscore the importance of individualized treatment plans and the need for further studies to define predictive biomarkers and therapeutic strategies in UV. Full article

Complement system inhibitors are emerging as promising therapies in nephrology, particularly for diseases where complement dysregulation is central to pathogenesis. This review summarizes the role of complement activation in kidney diseases and current evidence supporting complement-targeted treatments. As the complement system can be involved in the pathogenesis of different diseases to varying degrees, several research works have been conducted. These research efforts aim, firstly, to understand the mechanisms and role of complement cascade components in the most prevalent nephrological diseases and, secondly, to explore the potential of complement system inhibitors in these conditions and their possible clinical applications. Clinical trials demonstrate that complement inhibitors are most effective in conditions with significant complement involvement, such as C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These agents show variable benefits in diseases with partial complement activation, including lupus nephritis and ANCA-associated vasculitis, while their role in disorders like diabetic nephropathy and focal–segmental glomerulosclerosis remains limited. Complement inhibition offers a targeted strategy to prevent disease progression and improve outcomes in selected nephrological disorders. Full article

Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes—typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in about 30% of MC patients and it is a manifestation with poor prognosis. Nowadays, types II and III MC are the most common forms, often linked to autoimmune diseases like Sjögren’s syndrome and systemic lupus erythematosus, or to viral infections such as hepatitis B or persisting despite hepatitis C eradication. This review explores renal involvement in MC, offering a comprehensive perspective on current knowledge, including recent advances in pathophysiological understanding, evolving diagnostic strategies, and novel therapeutic approaches. In this context, “perspectives” refers to the growing recognition of the shifting epidemiology of MC—particularly the changing etiological landscape following hepatitis C virus eradication—as well as the integration of emerging clinical and pathological entities such as cryofibrinogenemia and monoclonal gammopathy of renal significance into diagnostic and management frameworks. Furthermore, the review highlights current therapeutic strategies recognized as most effective, emphasizing the importance of a multidisciplinary and multimodal approach that combines etiological treatment, B-cell–targeted therapy (notably rituximab), plasma exchange in selected cases, and comprehensive supportive care for renal and systemic complications. Moreover, the landscape of management could be enriched in future years, since clinical trials are ongoing to explore novel therapies for refractory or relapsing cases of MC with renal involvement. Full article

Glomerular diseases are a major cause of chronic kidney disease worldwide, yet epidemiological data from Eastern Europe, and Romania in particular, remain scarce. This study aimed to characterize the spectrum of biopsy-proven glomerulopathies in Romania through a multicenter national registry over a 10-year period. We retrospectively analyzed 4047 native kidney biopsies performed between 2014 and 2023 across four national nephrology reference centers. Patient demographics, clinical presentation, and histopathological diagnoses were collected and categorized into primary and secondary glomerular diseases, glomerulosclerosis, tubulointerstitial nephropathies, hereditary nephropathies, and vascular nephropathies. The mean patient age was 48 years, 54.8% were male, and 51.4% presented with nephrotic-range proteinuria. The most common primary glomerulopathies were membranous nephropathy (16.7%), immunoglobulin A nephropathy (15.6%), focal segmental glomerulosclerosis (8.8%), and membranoproliferative glomerulonephritis (10%). Among secondary glomerular diseases, lupus nephritis (9.3%), diabetic nephropathy (8.5%), and vasculitis (7.7%) were most frequent. Marked inter-center variability was observed, with a notably high prevalence of membranous nephropathy in Iași (31.1%). Over the study period, the incidence of focal segmental glomerulosclerosis increased while immunoglobulin A nephropathy declined. This study provides the first nationwide epidemiological assessment of biopsy-proven glomerular disease in Romania, revealing both similarities and distinctive differences compared to patterns reported in other European countries. Full article

Background: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody levels in patients with membranous nephropathy n= 18, focal and segmental glomerulosclerosis (FSGS) n = 25, lupus nephritis (LN) n = 17, IgA nephropathy n = 14, mesangial proliferative (non-IgA) glomerulonephritis n = 6, c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis n = 40, p (perinuclear)-ANCA vasculitis n = 16, and compared them with a healthy control group n = 22. Next, we observed the clinical course of the patients (creatinine, total protein, and albumin) up to 2 years and correlated the results with the level of antibodies. Results: The anti-PAR 1 antibody level was lower in membranous nephropathy and FSGS compared to the control group. Anti-PAR 1 antibody levels were higher in secondary compared to primary glomerulonephritis. Both anti-PAR 1 and anti-ACE 2 antibody levels correlated positively (in focal and segmental glomerulosclerosis) or negatively (in lupus nephritis) with total protein and albumin at different time points of observation. Anti-PAR 1 and anti-ACE 2 antibody levels correlated also with creatinine level at one time point of observation in IgA nephropathy. Anti-PAR 1 and anti-ACE 2 antibodies correlated with each other in membranous nephropathy, FSGS, and p- and c-ANCA vasculitis (p < 0.05). Conclusions: The anti-PAR 1 antibody level was lower in membranous nephropathy and focal and segmental glomerulosclerosis compared to the control group. Anti-PAR 1 antibody levels tend to be higher in secondary compared to primary glomerulonephritis. Full article

Sarcopenia is characterized by a loss of muscle mass and function, with significant implications for the physical performance of the affected people. Although commonly associated with aging, disease-related sarcopenia is of great clinical importance, particularly as it impacts disease progression and outcomes. Individuals with rheumatic diseases (RDs), including rheumatoid arthritis, systemic sclerosis, spondyloarthritides, systemic lupus erythematosus, fibromyalgia, myositis, or vasculitis, exhibit a high prevalence of sarcopenia, which exacerbates their clinical symptoms and contributes to poorer disease outcomes. Chronic inflammation influences muscle tissue degradation, causing a decline in physical performance. Apart from the apparent clinical manifestations, patients with RDs also use pharmacological treatments that negatively impact muscle mass further, increasing the risk of sarcopenia. Nutrition (diet and dietary supplements) and exercise interventions have been recommended as protective measures for sarcopenia as they may mitigate its adverse events. The present narrative review seeks to explore the methods used to assess sarcopenia in patients with RDs, its prevalence among them, and the challenges faced by the affected individuals, while critically assessing the appropriateness and limitations of current sarcopenia assessment tools in the context of RDs. Full article

T-follicular helper (Tfh) cells, a specialized subset of CD4⁺ cells, are the immune mediators connecting cellular and humoral immunity, as they lead B-cell proliferation within germinal centers, and orchestrate their response, including activation, class switching, and production of a diverse array of high-affinity antibodies. Their interactions with B cells is regulated by a wide complex of transcriptional and cytokine-driven pathways. A major contribution of Tfh cells to autoimmune diseases is through their production of cytokines, particularly IL-21, which supports the proliferation and differentiation of autoreactive B cells. Elevated levels of circulating Tfh-like cells and IL-21 have been observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) correlating strongly with disease severity and autoantibody levels. The feedback loop between Tfh cells and IL-21 or other signal pathways, such as Bcl-6, ICOS, and PD-1, not only sustains Tfh cell function but also drives the continuous expansion of autoreactive B cells, leading to chronic inflammation through the production of high-affinity pathogenic autoantibodies. By understanding these interactions, Tfh pathways may serve as potential therapeutic targets, with IL-21, ICOS, and PD1 blockades emerging as promising innovative therapeutic strategies to manage autoimmune diseases. Although a variety of studies have been conducted investigating the role of Tfh cells in SLE and RA, this review aims to reveal the gap in the literature regarding the role of such subpopulations in the pathogenesis of other autoimmune diseases, such as Anca-associated vasculitis (AAV), and express the need to conduct similar studies. Tfh cell-related biomarkers can be used to assess disease activity and transform autoimmune disease treatment, leading to more personalized and effective care for patients with chronic autoimmune conditions. Full article

Kidney transplantation is the most effective replacement therapy for kidney failure, providing the best outcomes in terms of patient survival and offering a better quality of life. However, despite the progressive improvement in kidney survival, the recurrence of original disease remains one of the most important causes of graft loss and a major challenge that requires clinical vigilance throughout the transplant’s duration. Additionally, the type and severity of recurrence affect both treatment options and graft survival. This is especially true for the recurrence of systemic diseases. In this narrative review, we will discuss the timing, frequency, severity, and treatment of post-transplant recurrence in three systemic diseases: lupus nephritis (LN), Antineutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (ANCA-GN), and Henoch–Schönlein purpura (HSP). The recurrence of lupus nephritis is less common than that of primary focal segmental glomerulosclerosis or C3 glomerulopathy. Its severity can range from mild mesangial to diffuse proliferative forms, with varying prognoses and treatment options, much like the original disease. In some patients with LN, as well as in those with ANCA-GN or HSP, the reactivation of the primary disease can affect other organs besides the kidneys, potentially leading to life-threatening conditions. These cases may require a multidisciplinary approach, making these transplants clinically more challenging. Extrarenal flare-ups often necessitate an increase in immunosuppression, which in turn raises the risk of infections. In these autoimmune diseases, the role of immunological tests in determining the timing of kidney transplants remains a topic of ongoing debate. However, elevated levels of certain immunological markers, such as anti-dsDNA antibodies, ANCA titers, or serum immunoglobulin A may indicate a reactivation of the disease, suggesting the need for more intensive patient monitoring. Full article

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder. Neuropsychiatric manifestations are frequently observed and are associated with increased morbidity and reduced quality of life. Magnetic resonance imaging (MRI) is the neuroimaging procedure of choice for investigation. High-resolution vessel wall imaging (HRVWI) is a neuroimaging methodology that allows active mapping of pathophysiological processes involving brain vessel walls. Methods: To exemplify the importance of HRVWI and its usefulness in patients with SLE, we carried out a scoping review (following PRISMA guidelines) using the PubMed and Embase databases. Results: We retrieved 10 studies that utilized HRVWI in neuropsychiatric SLE, including a total of 69 patients. The majority, 84% (58/69), were women, with ages ranging between 16 and 80 years (average 38.4 years). Approximately 46.3% (32/69) of patients had white matter lesions in the brain at the time of investigation, and 77% (53/69) had normal magnetic resonance angiography. Treatment with immunosuppressants led to the resolution of the majority of the findings. Conclusions: Imaging plays an important role in investigating neuropsychiatric SLE. HRVWI analysis is gaining more importance, with its ability to identify inflammation even if angiographic MRI sequences (3D TOF) are normal, allowing the institution of early immunosuppressant treatment and resolution of symptoms. Full article

The complement cascade and Neutrophil Extracellular Traps (NETs) represent fundamental tools in protecting the host from foreign pathogens. Complement components and relative fragments, classically assigned to the innate immunity, represent a key link with the humoral immune response. NETs are a crucial component of the innate immune response, consisting of chromatin release from activated neutrophils. These web-like structures facilitate pathogen entrapment and elimination through proteolytic degradation and antimicrobial effectors. Previous findings suggested complement components and NETs have a significant role in the pathogenesis of several diseases characterized by inflammation, such as autoimmune and infectious diseases. However, the crosstalk between NETs and the complement cascade has only recently been investigated, and several aspects still need to be fully clarified. Recent evidence seems to suggest a bidirectional link between the complement cascade and NETosis. We here present the interaction between complement components and NETs in specific autoimmune diseases that mostly affect the kidney, such as systemic lupus erythematosus, Antineutrophilic Cytoplasmic Antibody (ANCA)-associated vasculitis and antiphospholipid syndrome. The mechanisms reported here may represent specific targets for the development of possible therapeutic strategies. Full article

Background: The Safety and Immunogenicity of COVID-19 Vaccines in Systemic Autoimmune-Mediated Inflammatory Diseases (SUCCEED) study was created to better understand COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Knowing the frequency of COVID-19 breakthrough infections is important, particularly in IMID. Our objective was to assess these events in IMID. Methods: We prospectively studied IMID participants who had received ≥three COVID-19 vaccine doses. Individuals provided saliva samples monthly (September 2022 to August 2023). These were evaluated by polymerase chain reaction (PCR) for SARS-CoV-2. We also assessed antibodies against SARS-CoV-2 (anti-spike, SmT1, receptor binding domain, RBD, and nucleocapsid, NP) based on dried blood spots. Multivariable general estimating equation regression produced odd ratios (OR) for PCR SARS-CoV-2 positivity, related to demographics, immunosuppressives, and antibody levels. Results: Diagnoses included rheumatoid arthritis RA (N = 161, 44% of the total), systemic lupus, psoriatic arthritis, spondylarthritis, vasculitis, systemic sclerosis, and inflammatory bowel disease. Of the 366 participants, most were taking immunosuppressive medication. Of 1266 saliva samples, 56 (5.1%) were positive for SARS-CoV-2 on PCR. Higher anti-SmT1 antibodies were inversely associated with SARS-CoV-2 detection on PCR (adjusted OR 0.66, 95% confidence interval 0.45–0.97). Antibodies to SmT1, RBD, and NP were correlated and thus could not be included in a single model, but when anti-RBD was used in place of anti-SmT1, the results were similar. No other factor (including prior COVID-19 infection) was clearly associated with SARS-CoV-2 detection. Conclusions: This is the first study of SARS-CoV-2 in a large prospective cohort of triple (or more) vaccinated individuals with IMIDs. Anti-SmT1 antibodies appeared to be protective against later SARS-CoV-2 positivity, although recent past infection was not clearly related. This suggests the importance of maintaining robust vaccine-induced immunity through vaccination in IMID. Full article

Background: Anti-ETAR (endothelin A receptor) antibodies and anti-CXCR3 (C-X-C motif chemokine receptor 3) antibodies are types of non-HLA (human leukocyte antigens) antibodies that could have some influence on the course of glomerulonephritis. The authors aimed to study the influence of these antibodies’ levels on the course of specific glomerulonephritis types. Methods: We evaluated the anti-ETAR and anti-CXCR3 antibody levels in the serum of patients with membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (FSGS) (n = 25), systemic lupus erythematosus (n = 17), IgA nephropathy (n = 14), mesangiocapillary glomerulonephritis (n = 6), anti-neutrophil cytoplasmic antibodies (c-ANCA) vasculitis (n = 40), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and we compared their levels with the control group (n = 22). Next, we observed the patients’ clinical parameters (serum creatinine, albumin, total protein) for 2 years and checked the correlation of the clinical course markers with basic receptor antibody level. Results: Our results indicate lower anti-ETAR antibody levels in patients with FSGS and IgA nephropathy compared to the control group. Both types of antibodies correlated with creatinine levels after 2 years of observation in IgA nephropathy. Both types of antibodies seemed to negatively influence the total protein and albumin levels in systemic lupus erythematosus. Conclusions: This prospective observation showed that anti-ETAR and anti-CXCR 3 antibody levels are connected with the course of IgA nephropathy and lupus nephritis. Full article

Background/Objectives: Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are commonly used for allergic rhinitis (AR), yet limited research has directly compared their effects on quality of life (QoL). We aimed to assess QoL differences between SLIT and SCIT recipients. As both forms of immunotherapy have reported benefits, we hypothesize that patients undergoing SLIT and SCIT will have comparable QoL improvements. Methods: A cohort study included patients with AR treated with immunotherapy from 2018 to 2022. Patients with obstructive sleep apnea, primary ciliary dyskinesia, cystic fibrosis, vasculitis, rheumatoid arthritis, sarcoidosis, or lupus were excluded. QoL was evaluated using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at multiple time points. Demographics, additional therapies, and allergen sensitivities were recorded. Data were analyzed using SPSS Statistics. Results: A total of 41 participants were eligible for inclusion. Both SLIT and SCIT groups exhibited reductions from baseline RQLQ scores. Within SLIT recipients, 5/7 RQLQ domains significantly improved. SCIT recipients showed significant QoL enhancement in 3/7 domains. The mean difference between SLIT and SCIT cohorts was −0.18 (p = 0.57, d = −0.18, 95% CI [−0.79, 0.43] at a mean treatment time of 18 months. Conclusions: SLIT and SCIT showed comparable RQLQ score reductions after 18 months of therapy, suggesting similar QoL benefits between the two treatment paradigms. Further investigation is needed to explore SLIT vs. SCIT differences in long-term QoL improvements beyond two years. Full article

Epitope spreading is a critical mechanism driving the progression of autoimmune glomerulonephritis. This phenomenon, where immune responses broaden from a single epitope to encompass additional targets, contributes to the complexity and severity of diseases such as membranous nephropathy (MN), lupus nephritis (LN), and ANCA-associated vasculitis (AAV). In MN, intramolecular spreading within the phospholipase A2 receptor correlates with a worse prognosis, while LN exemplifies both intra- and intermolecular spreading, exacerbating renal involvement. Similarly, ANCA reactivity in AAV highlights the destructive potential of epitope diversification. Understanding these immunological cascades reveals therapeutic opportunities—targeting early epitope spreading could curb disease progression. Despite promising insights, the clinical utility of epitope spreading as a prognostic tool remains debated. This review provides a complete overview of the current evidence, exploring the dual-edged nature of epitope spreading, the intricate immune mechanisms behind it, and its therapeutic implications. By elucidating these dynamics, we aim to pave the way for more precise, targeted interventions in autoimmune glomerular diseases. Full article