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1.
Microorganisms ; 12(8)2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39203514

RESUMO

Immunology and microbiology research has witnessed remarkable growth and innovation globally, playing a pivotal role in advancing our understanding of immune mechanisms, disease pathogenesis, and therapeutic interventions. This manuscript presents a comprehensive exploration of the key areas in immunology research, spanning from the utilisation of bacterial proteins as antibody reagents to the intricate realms of clinical immunology and disease management. The utilisation of bacterial immunoglobulin-binding proteins (IBPs), including protein A (SpA), protein G (SpG), and protein L (SpL), has revolutionised serological diagnostics, showing promise in early disease detection and precision medicine. Microbiological studies have shed light on antimicrobial resistance patterns, particularly the emergence of extended-spectrum beta-lactamases (ESBLs), guiding antimicrobial stewardship programmes and informing therapeutic strategies. Clinical immunology research has elucidated the molecular pathways underlying immune-mediated disorders, resulting in tailored management strategies for conditions such as severe combined immunodeficiency (SCID), neuropsychiatric systemic lupus erythematosus (NPSLE), etc. Additionally, significant efforts in vaccine development against tuberculosis and HIV are highlighted, underscoring the ongoing global pursuit of effective preventive measures against these infectious diseases. In summary, immunology and microbiology research have provided significant contributions to global healthcare, fostering collaboration, innovation, and improved patient outcomes.

2.
Rev. colomb. reumatol ; 29(2): 79-84, Apr.-June 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1423909

RESUMO

ABSTRACT Introduction: Transcranial Doppler ultrasonography (TCD) is a technique that allows measurement of blood flow from the basal intracerebral vessels. It is relatively inexpensive, non-invasive, can be performed at the bedside, and allows monitoring in acute emergency settings and for prolonged periods with a high temporal resolution, making it ideal for studying the haemodynamics within the intracranial arteries in neuro-Behcet's disease (NBD) and neuro-psychiatric lupus (NPSLE). Our aim was to assess the cerebral haemodynamic patterns in patients with NBD and NPSLE using TCD, while brain lesions were examined using magnetic resonance imaging (MRI). Material and methods: Case-control prospective study of 30 neuro-Behcet's disease patients, 25 neuro-psychiatric lupus patients and 26 healthy age-matched volunteers. All patients and healthy controls were examined by TCD. Only the groups of patients underwent cranial magnetic resonance imaging (MRI). Results: Transcranial Doppler (TCD) values for middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA) in NBD, NPSLE and control groups were measured. The results showed that there was a significant decrease in mean blood flow velocities in all the arteries examined in NBD and NPSLE patients. There was also a significant increase in the pulsatile index of PCA, VA and BA between NBD and NPSLE patients. The same results were obtained when comparing NBD versus controls. However, there was no significant difference between the NPSLE patients and the control group. The MRI lesions described were parenchymal lesions in 14 patients (46.7%), and vascular lesions in 4 patients (13.3%). Vascular lesions co-existed with parenchymal lesions (mixed lesion). Parenchymal lesions were in white matter (40%), thalamus (26.7%), brain stem (26.7%) and cerebellum (20%). While, in NPSLE, 23 patients were normal (92%) and only two patients had a vascular lesion (8%). Conclusion: There was a significant decrease in mean blood flow and a significant increase in the pulsatile index among both NBD and NPSLE patients, according to the TCD values.


Assuntos
Humanos , Masculino , Feminino , Adulto , Infecções , Doenças Estomatognáticas , Infecções do Sistema Nervoso Central , Síndrome de Behçet , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Doenças da Boca
3.
Clin Rheumatol ; 41(6): 1859-1866, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35149930

RESUMO

INTRODUCTION/OBJECTIVES: Patients with systemic lupus erythematosus (SLE) may have neurological complications, characterizing neuropsychiatric lupus (NPSLE). Studies have investigated alternative therapies such as vitamin D, which has an effect on the immune system and brain, to control manifestations of SLE. Experimental lupus models may be a good alternative to best study the immunological mechanisms underlying the development of NPSLE, and the animal model of pristane-induced lupus (PIL) may mimic SLE symptoms in humans. Our objective was to evaluate central nervous system involvement and vitamin D supplementation in a PIL model. METHOD: Female BALB/c mice were divided into controls (CO; n = 7), PIL (n = 9), and PIL supplemented with vitamin D (VD; n = 7). The hippocampus area was measured and immunoassays were performed for detecting vitamin D receptor (VDR) and IgG. RESULTS: The PIL group had a higher hippocampal IgG infiltrate when compared to the CO group. Vitamin D showed potential for reducing IgG infiltration. The hippocampus area was similar in all groups. No differences in VDR expression were observed between groups. A positive correlation was observed between the expression of VDR and IgG in the hippocampus. CONCLUSION: Our data suggest that increased IgG infiltration into the hippocampus indicated an inflammatory process that may have stimulated VDR expression. Key Points • IgG infiltrate is higher in PIL animals than controls • VDR increases along with IgG infiltrate • Hippocampal VDR expression does not increase with vitamin D supplementation.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Animais , Feminino , Hipocampo/metabolismo , Humanos , Imunoglobulina G , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Camundongos , Receptores de Calcitriol/metabolismo , Terpenos , Vitamina D
4.
BMC Biol ; 18(1): 164, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158444

RESUMO

BACKGROUND: Cognitive dysfunction (CD) is common among patients with the autoimmune disease systemic lupus erythematosus (SLE). Anti-ribosomal P autoantibodies associate with this dysfunction and have neuropathogenic effects that are mediated by cross-reacting with neuronal surface P antigen (NSPA) protein. Elucidating the function of NSPA can then reveal CD pathogenic mechanisms and treatment opportunities. In the brain, NSPA somehow contributes to glutamatergic NMDA receptor (NMDAR) activity in synaptic plasticity and memory. Here we analyze the consequences of NSPA absence in KO mice considering its structural features shared with E3 ubiquitin ligases and the crucial role of ubiquitination in synaptic plasticity. RESULTS: Electrophysiological studies revealed a decreased long-term potentiation in CA3-CA1 and medial perforant pathway-dentate gyrus (MPP-DG) hippocampal circuits, reflecting glutamatergic synaptic plasticity impairment in NSPA-KO mice. The hippocampal dentate gyrus of these mice showed a lower number of Arc-positive cells indicative of decreased synaptic activity and also showed proliferation defects of neural progenitors underlying less adult neurogenesis. All this translates into poor spatial and recognition memory when NSPA is absent. A cell-based assay demonstrated ubiquitination of NSPA as a property of RBR-type E3 ligases, while biochemical analysis of synaptic regions disclosed the tyrosine phosphatase PTPMEG as a potential substrate. Mice lacking NSPA have increased levels of PTPMEG due to its reduced ubiquitination and proteasomal degradation, which correlated with lower levels of GluN2A and GluN2B NMDAR subunits only at postsynaptic densities (PSDs), indicating selective trafficking of these proteins out of PSDs. As both GluN2A and GluN2B interact with PTPMEG, tyrosine (Tyr) dephosphorylation likely drives their endocytic removal from the PSD. Actually, immunoblot analysis showed reduced phosphorylation of the GluN2B endocytic signal Tyr1472 in NSPA-KO mice. CONCLUSIONS: NSPA contributes to hippocampal plasticity and memory processes ensuring appropriate levels of adult neurogenesis and PSD-located NMDAR. PTPMEG qualifies as NSPA ubiquitination substrate that regulates Tyr phosphorylation-dependent NMDAR stability at PSDs. The NSPA/PTPMEG pathway emerges as a new regulator of glutamatergic transmission and plasticity and may provide mechanistic clues and therapeutic opportunities for anti-P-mediated pathogenicity in SLE, a still unmet need.


Assuntos
Antígenos de Superfície/genética , Proteínas do Tecido Nervoso/genética , Neurônios/fisiologia , Proteína Tirosina Fosfatase não Receptora Tipo 4/genética , Receptores de N-Metil-D-Aspartato/genética , Animais , Antígenos de Superfície/metabolismo , Masculino , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal , Proteína Tirosina Fosfatase não Receptora Tipo 4/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Ubiquitinação
5.
Expert Rev Clin Immunol ; 15(4): 407-416, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30632405

RESUMO

INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice. Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events. Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Neuroimagem/métodos , Autoanticorpos/sangue , Biomarcadores/sangue , Progressão da Doença , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Fatores de Risco
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