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Norberto Ortego-Centeno

Publications and source records attributed to Norberto Ortego-Centeno.

10 recordsLinked to original sources
PubMed2025

Novel Insights into the Clinical Features, Genetic Spectrum and Clonal Evolution of Patients Carrying NLRP3 Mosaicism.

NLRP3 mosaicism is a well-established mechanism causing the monogenic autoinflammatory disease named cryopyrin-associated periodic syndromes (CAPS). The number of reported patients with NLRP3 mosaicism is small, and the knowledge about the long-term disease behavior is limited. Herein we assembled the largest cohort of individuals with NLRP3 mosaicism reported to date to obtain additional evidence that strengthens the understanding of this disease. The novel genetic data were obtained by using Sanger and next-generation sequencing methods, whereas in vitro analyses determined the functional consequences of detected variants. A total of seventeen individuals with NLRP3 mosaicism were enrolled, with 16/17 experiencing different CAPS phenotypes. An overrepresentation of late-onset forms was detected (37.5%). Overall, clinical manifestations, analytical results, and outcomes of treatments were markedly similar to those detected in patients with germline variants. A large mutational diversity was identified, with 16 different variants among 17 individuals. Two main patterns of mosaicism (extended vs. myeloid-restricted) were detected, with the last one overrepresented in the late-onset group. The evaluation of mosaicism over time identified three different patterns, being the group with stable mosaicism the largest one. Collected evidence supports the marked similarities among patients carrying somatic or germline NLRP3 variants. The overrepresentation of NLRP3 mosaicism in late-onset forms should be considered in patients with inflammatory manifestations starting in adulthood. Analysis of mosaicism at the biological level confirms the two known patterns of corporal distribution and reveals that mosaicism remains stable over time in most patients, but it may also vary during the course of the disease.

Humans↗
PubMed2006

Proteomic analysis of plasma from patients with systemic lupus erythematosus: increased presence of haptoglobin alpha2 polypeptide chains over the alpha1 isoforms.

In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hpalpha polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2-2, or Hp 2-1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0 625 (Hp(2)), 0.281 (Hp(1S)), and 0.093 (Hp(1F)) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp(2)), 0.233 (Hp(1S)), and 0.033 (Hp1(1F)), which clearly indicated an increased frequency of Hp(2), a similar proportion of Hp(1S) and a diminished proportion of Hp(1F) in SLE patients compared with that in healthy controls. Preferential Hpalpha2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders.

Biomarkers↗
PubMed2005

Treatment of therapy-resistant sarcoidosis with adalimumab.

A possible role of tumor necrosis factor alpha (TNFalpha) in the pathomechanism of sarcoidosis must be considered in the analysis of this disorder since elevated concentrations of this cytokine have been found. In addition, TNFalpha expression could be demonstrated in sarcoid granulomata [1]. It is well known that TNFalpha plays a crucial role in granulomatous inflammation, e.g., in mycobacterial diseases [2]. Therefore, TNFalpha blockade is a potential approach in the therapy for sarcoidosis. Up to now, various cases of therapy-resistant sarcoidosis treated with anti-TNFalpha (infliximab and etanercept) have been reported [3-8]. Here, we describe successful treatment using adalimumab, a human recombinant immunoglobulin (Ig) G1 anti-TNF monoclonal antibody [9].

Adalimumab↗
PubMed2005

Transient global amnesia in a patient with high and persistent levels of antiphospholipid antibodies.

Cerebrovascular disease is one of the most common symptoms associated with anticardiolipin antibodies (ACA) and lupus anticoagulant (LA), usually in the form of ischemic stroke. However, many other neurologic disorders have been described in patients with antiphospholipid syndrome or ACA. So far, the precise relation between the presence of antibodies and the development of the disease in many of these cases remain unknown. Transient global amnesia (TGA) is an infrequent neurologic disturbance whose precise pathophysiology is not known. It is characterized by a sudden inability to acquire new information, usually lasting no more than 12 h, and it is not accompanied by any other focal neurological signs or symptoms. We report a patient with TGA with persistent and high levels of ACA and LA and suggest that in patients with TGA, investigation of the possible presence of ACA and/or LA may be warranted because a higher prevalence of TGA in the patients with antiphospholipidic syndrome with respect to the general population may lead to further insights into pathogenesis of neurologic disease associated with antiphospholipidic antibodies.

Amnesia, Transient Global↗
PubMed2005

Increased association of CD38 with lipid rafts in T cells from patients with systemic lupus erythematosus and in activated normal T cells.

In this study we have determined whether there is a relationship between CD38 expression on T cells, its distribution in different membrane microdomains, and T cell activation in SLE patients. The data show that CD38 expression is augmented in ex vivo CD3+, CD4+, CD8+, and CD25+ SLE T cells, which correlates with its increased insolubility in Brij 98 detergent, and its translocation into lipid rafts. Moreover, SLE T cells show an altered CD4:CD8 ratio, which is due to a decreased proportion of CD4+ T cells and a concomitant increase in the proportion of CD8+ T cells. These data are consistent with the increased CD38 expression and lipid raft formation, and the significant reduction in the CD4:CD8 ratio observed in mitogen-stimulated normal T cells as compared with that in ex vivo untouched normal T cells. Increased expression of CD38 in floating rafts from SLE T cells, or from activated normal T cells may modulate TCR signaling by providing or sequestering signaling molecules to the engaged TCR.

ADP-ribosyl Cyclase 1↗
PubMed2005

Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. RESULTS: The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi-square test with 2 x 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15-1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05-2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01-2.09]). CONCLUSION: These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.

Adult↗