Publications by authors named "Nozal P"

Article Synopsis
  • The EXXELERATE study found that patients with rheumatoid arthritis (RA) and high rheumatoid factor (RF) levels (>203 IU/mL) had worse clinical outcomes when treated with adalimumab (ADL).
  • This new study aimed to investigate how RF levels affect the serum levels of TNF inhibitors and the risk of secondary nonresponse in RA patients.
  • Results showed that high RF levels were linked to lower drug levels and a significantly higher risk of treatment discontinuation in patients using infliximab (IFX) or ADL, but not in those treated with certolizumab pegol (CZP).
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Celiac disease (CeD) is an autoimmune condition triggered by gluten in genetically predisposed individuals, affecting all ages. Intestinal permeability (IP) is crucial in the pathogenesis of CeD and it is primarily governed by tight junctions (TJs) that uphold the intestinal barrier's integrity. The protein zonulin plays a critical role in modulating the permeability of TJs having emerged as a potential non-invasive biomarker to study IP.

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  • Certolizumab pegol (CZP) maintains stable serum levels in rheumatoid arthritis (RA) patients, regardless of baseline rheumatoid factor (RF) status, while treatment with infliximab (IFX) and adalimumab (ADL) shows varying serum drug levels based on RF levels.
  • A study of 170 RA patients found that high baseline RF levels were associated with lower serum drug levels for IFX and ADL, but not CZP, after six months.
  • Patients with high RF levels experienced higher rates of treatment discontinuation due to non-response with IFX and ADL compared to those receiving CZP, highlighting potential treatment differences based on RF levels.
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  • The study aimed to explore the formation of anti-drug antibodies (ADA) against infliximab (IFX) and how these relate to drug levels and patient outcomes in rheumatoid arthritis (RA) and spondyloarthritis (SpA).
  • Serum samples were collected from 106 patients over time, and two different assays were used to detect ADA and measure IFX levels, with the drug-tolerant assay identifying ADA earlier than the drug-sensitive assay.
  • Results showed that patients who developed ADA earlier had lower levels of IFX and shorter drug survival, suggesting early immunogenicity affects the treatment's effectiveness.
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  • Barraquer-Simons syndrome (BSS) is a rare acquired lipodystrophy leading to significant loss of upper body fat, particularly affecting the face and arms, with a possible autoimmune origin.
  • This study evaluated clinical and immunological data from 26 BSS patients to refine diagnostic tools and identify potential triggers or genetic links.
  • Key findings revealed most patients experienced fat loss in childhood, with a notable prevalence of autoimmune markers and metabolic conditions, suggesting BSS is commonly connected to other autoimmune diseases.
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Introduction: Multiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release autoreactive antibodies against myelin. The aim of the present study was to investigate whether extracellular vesicles (EVs) mediate delivery of myelin autoreactive antibodies from peripheral B cells against oligodendrocytes in multiple sclerosis (MS) and to analyze whether these EVs could mediate demyelination .

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  • *%! Conducted with 86 patients using various biologic drugs, the study found that 86% of patients developed SARS-CoV-2 antibodies compared to 100% in healthy controls, with those on rituximab showing the weakest antibody response.
  • *%! Although 14% of patients had no detectable antibodies, a subset of 30 patients evaluated for cellular response showed that 11 had a positive response, particularly those on rituximab,
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  • Inborn errors of immunity (IEI) are conditions that weaken the immune system, making it challenging to evaluate infection risk and vaccine responses, particularly after SARS-CoV-2 vaccination.
  • This study focused on analyzing the immune responses of IEI patients by measuring specific memory B cells and antibodies both before and after vaccination.
  • Results showed varying immune responses in IEI patients, with some exhibiting adequate responses, while others demonstrated significant deficiencies, highlighting the unpredictable nature of humoral and T-cell responses in this group.
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The field of Autoimmune Neurology is expanding rapidly, with new neural antibodies being identified each year. However, these disorders remain rare. Deciding when to test for these antibodies, when and what samples are to be obtained, how to handle and study them correctly, and how to interpret test results, is complex.

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Background: Immune responses to vaccines against severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 are variable. In the absence of disease, youngsters are expected to better react to vaccines than adults. Nevertheless, chronic immunosuppression in transplant recipients may impair their capability to generate protection.

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Acquired generalized lipodystrophy (AGL) is a rare condition characterized by massive loss of adipose tissue through the body, causing severe metabolic complications. Autoimmune destruction of adipocytes is strongly suspected based on the frequent association of AGL with autoimmune disorders. In 2018, autoantibodies against perilipin 1 (PLIN1) were identified in three patients with autoimmune-associated AGL.

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Background: In recent years, cases have been reported in which unexpected systemic hypersensitivity reactions occurred in patients dialyzed with polysulfone- or polyethersulfone-biocompatible membranes in the absence of other risk factors. The pathomechanisms involved in these reactions are largely unknown.

Objective: To characterize hypersensitivity reactions to polysulfone hemodialysis using clinical and laboratory data and to identify biomarkers suitable for endotype identification and diagnosis.

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The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination.

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Complement overactivation has been reported in most patients with Barraquer-Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed.

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Objective: To evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA).

Methods: Longitudinal observational study involving 81 patients with axSpA monitored during infliximab therapy. Serum ITL were measured before starting infliximab treatment and at weeks 2 (W2), W6 and W12 of treatment.

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Article Synopsis
  • * 127 patients were monitored, and findings revealed that 24% of them developed ADA, with age playing a significant role in this relationship.
  • * In individuals over 55 years old, higher BAFF levels (≥ 1034 pg/mL) were strongly predictive of ADA development, suggesting that BAFF concentration may help to anticipate immunogenicity in older patients undergoing TNFi therapy.
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Haemolytic Uraemic Syndrome associated with infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients.

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Biosimilars are replacing originator compounds due to their similar effectiveness, safety and pharmacokinetics. Our objective was to compare the differences in pharmacokinetics and clinical outcomes between the originator infliximab (Ifx) and the biosimilar CT-P13 in a patient cohort with inflammatory bowel disease (IBD). Our cohort study included 86 patients from a historical and a prospective cohort from the start of infliximab treatment to 22 weeks later.

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TNF inhibitors (TNFis) are widely used for the treatment of rheumatoid arthritis (RA), although the response rates to this therapy in patients with RA remains heterogeneous and < 50% achieve remission (REM). To analyze baseline peripheral blood leukocytes profiles in order to search for biomarkers identifying patients who will most likely not achieve REM under TNFi treatment. A prospective bi-center pilot study including 98 RA patients treated with TNFis and followed-up during 6 months.

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  • Barraquer-Simons syndrome (BSS) is a rare condition where there is a selective loss of fat from the upper body while retaining fat in the lower body, but its cause remains unclear.
  • A study monitored an 11-year-old girl with BSS over 5 years, examining her clinical condition and various immunological factors, while noting a progression of her fat loss and detecting no significant abnormalities besides this.
  • Findings revealed that there was hyperactivation of the complement system in her adipose tissue, indicated by specific immune markers, suggesting that this may contribute to the fat loss observed in BSS.
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Following the publication of the original article [1], the authors have requested to amend the Abstract and Discussion section as follows.

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Background: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated.

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Acquired angioedema due to C1-inhibitor (C1INH) deficiency (AAE) is caused by secondary C1INH deficiency leading to bradykinin-mediated angioedema episodes. AAE typically presents in adulthood and is associated with B cell lymphoproliferation. Anti-C1INH autoantibodies (antiC1INHAbs) are detectable in a subset of AAE cases and considered a hallmark of the disease.

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