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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 776-782, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750817

RESUMO

Objective To prepare inducible lupus model mice and investigate the effect of nuclear autoantigenic sperm protein (NASP) gene mutation on the autoimmune response of mice with induced systemic lupus erythematosus (SLE). Methods The 3-month wild-type B6 (B6-WT) mice were used as a control group and the NASP mutant B6 (B6-NASPM) mice as an experimental group. Mouse spleen lymphocytes were activated with concanavalin A (ConA), and the DNA was extracted as autoantigen. B6-WT mice and B6-NASPM mice were immunized three times. Serum anti-double stranded DNA (dsDNA) IgG levels were detected by ELISA. Renal lesions were detected by HE staining. Immunohistochemical staining was performed to detect the deposition of IgG and complement C3 in the renal tissues. Flow cytometry was applied to compare the spleen lymphocyte subsets in B6-WT and B6-NASPM mice and to explore the mechanism of NASP gene mutation affecting the immune response in mice. Results Compared with B6-WT mice, B6-NASPM mice showed no significant changes in body weight, kidney index and spleen index; serum anti-dsDNA IgG levels significantly increased; glomerular cell proliferation was obvious and the deposition of IgG and C3 in the renal tissues increased. The proportion of spleen CD3+ T cells and natural killer (NK) cells decreased, while the proportion of CD19+ B cells and regulatory B cells (Breg) increased. Conclusion Mutation in the NASP gene can increase the levels of anti-dsDNA IgG antibodies, promote cell proliferation in the glomerulus of the kidney, deposition of IgG antibodies and complement C3, alter the proportion of immune cells in the spleen and aggravate the autoimmune response in lupus model mice.


Assuntos
Autoantígenos/genética , Autoimunidade , Lúpus Eritematoso Sistêmico/genética , Proteínas Nucleares/genética , Animais , Anticorpos Antinucleares/sangue , Complemento C3/imunologia , Modelos Animais de Doenças , Glomérulos Renais/imunologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Mutação , Baço/imunologia
2.
Autoimmun Rev ; 18(10): 102371, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31415907

RESUMO

Systemic lupus erythematosus (SLE) is associated with a high burden of cardiovascular disease (CVD), which is in part imputed to classical vascular risk factors such as hypertension. Hypertension is frequent among patients with SLE and studies show it is more prevalent in SLE patients than in people without SLE. Despite the high frequency of hypertension in SLE patients, the pathophysiological mechanisms underlying the development of hypertension remain poorly understood. 24-h ambulatory blood pressure monitoring has emerged as a valuable tool in determining blood pressure (BP) in SLE patients in whom hypertension has been associated with damage accrual, stroke and cognitive dysfunction. Although prevalent, current guidelines neglect the specific management of hypertension in SLE patients in their recommendations. This review discusses the mechanisms that may lead to hypertension and the literature evaluating hypertension screening and management in SLE patients.


Assuntos
Hipertensão/complicações , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/patologia , Humanos , Prognóstico , Fatores de Risco
3.
DNA Cell Biol ; 38(10): 1040-1047, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414895

RESUMO

The helper T cell 9 (Thelper-9, Th9), as a functional subgroup of CD4+T cells, was first discovered in 2008. Th9 cells expressed transcription factor PU.1 and cytokine interleukin-9 (IL-9) characteristically. Recent researches have shown that the differentiation of Th9 cells was coregulated by cytokine transforming growth factor ß, IL-4, and various transcription factors. Th9 cells, as a new player, played an important role in various immune-related diseases, including tumors, inflammatory diseases, parasite infection, and other diseases. In this article, we summarize the related research progress and discuss the possible prospect.


Assuntos
Interleucina-9/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Neoplasias/imunologia , Proteínas Proto-Oncogênicas/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Transativadores/imunologia , Fator de Crescimento Transformador beta/imunologia , Animais , Diferenciação Celular , Fator de Transcrição GATA3/deficiência , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Regulação da Expressão Gênica , Humanos , Inflamação , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-9/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Knockout , Neoplasias/genética , Neoplasias/patologia , Proteínas Proto-Oncogênicas/genética , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/imunologia , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/patologia , Transativadores/genética , Fator de Crescimento Transformador beta/genética
5.
J Biol Regul Homeost Agents ; 33(3): 669-673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31195792

RESUMO

Systemic lupus erythematosus (SLE), is a complex chronic inflammatory autoimmune disease, with rheumatological manifestations, which afflicts mainly women. SLE presents various heterogeneous clinical aspects and different pathogeneses and involves the production of anti- DNA autoantibodies which are deposited as immune complexes in various organs and tissues, provoking inflammation. These diseases cause multiple tissue and organ damage in arthritis, skin lesions, hematologic changes, renal and neurologic disorders, and others (Table I). In SLE, serum contains anti-nucleus antibodies and anti-DNA antibodies that can be important biomarkers for patients suffering from this disease.


Assuntos
Inflamação/patologia , Lúpus Eritematoso Sistêmico/patologia , Mastócitos/citologia , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Humanos
6.
Autoimmun Rev ; 18(8): 751-760, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181324

RESUMO

Neutrophils derive from hematopoietic stem cells (HSCs) with systemic inflammation driving their activation and differentiation to myeloid progenitors to ensure enhanced myelopoiesis. Epigenetic reprograming and re-education of these HSCs produces neutrophils primed towards elimination of pathogens and increased inflammatory response. Neutrophils -an important component of acute inflammation- are not present in chronic inflammatory tissues leading to the false assumption that they may not be as important for the latter. Activated neutrophils may release Neutrophil Extracellular Traps (NETs) during a distinct form of cell death, named NETosis; NETs are rich in bioactive molecules that promote thrombosis (including atherothrombosis), inflammation and fibrosis. Thus, although neutrophils may not be present in chronic inflammatory lesions, their remnants may amplify the inflammatory response beyond their short life-span in the tissues. Herein, we review current evidence supporting a role of neutrophils and NETosis in tissue injury and dysfunction in systemic autoimmunity using as disease paradigms Systemic Lupus Erythematosus (SLE) and the ANCA-associated vasculitides (AAV). We also discuss the mechanisms involved and their potential as targets for novel therapy and drug repositioning.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Neutrófilos/imunologia , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Morte Celular , Diferenciação Celular , Armadilhas Extracelulares/imunologia , Fibrose , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/terapia , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Mielopoese , Neutrófilos/patologia
7.
Anticancer Res ; 39(6): 3003-3008, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177141

RESUMO

BACKGROUND: Various immune-related adverse events (irAEs) have been reported to be associated with the use of immune checkpoint inhibitors. We report a case of a patient with lung cancer treated with nivolumab who developed a bullous eruption and give a systematic review of the literature on irAEs in patients treated with immune checkpoint inhibitors for lung cancer. CASE REPORT: A patient with lung adenocarcinoma developed a non-specific skin lesion at the time of his cancer diagnosis followed by flare episodes until the eighth cycle of nivolumab, when he developed a bullous lupus. As the first eruption had started a few months after his cancer diagnosis and was exacerbated during immunotherapy, a paraneoplastic origin is discussed. Since the patient also presented with flares under nivolumab, we reviewed reported irAEs. No bullous lupus was found but to date, 33 cases of paraneoplastic lupus and two of lupus erythematosus have been reported. CONCLUSION: To our knowledge, this is the first description of a bullous lupus exacerbated by nivolumab.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Vesícula/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Lúpus Eritematoso Sistêmico/induzido quimicamente , Nivolumabe/efeitos adversos , Biópsia , Vesícula/patologia , Humanos , Lúpus Eritematoso Sistêmico/patologia , Pessoa de Meia-Idade
8.
Brain Nerve ; 71(5): 483-491, 2019 May.
Artigo em Japonês | MEDLINE | ID: mdl-31088997

RESUMO

Neuropathologic alterations of neuropsychiatric systemic lupus erythematosus (NPSLE) are characterized by small vessel changes such as endothelial proliferation, fibrosis, hyalinization, fibrinoid necrosis, and thrombus formation. Pathologic ischemic and hemorrhagic changes. In some instances, vasculitis and perivascular infiltration of inflammatory cells are seen. In the spinal cord, degenerative changes of entire margin of the spinal cord may also be present.


Assuntos
Lúpus Eritematoso Sistêmico/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Humanos , Neuropatologia
9.
Brain Nerve ; 71(4): 317-321, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-30988213

RESUMO

The cutaneous manifestations of lupus erythematosus (LE) include LE-specific and LE-nonspecific skin lesions. LE-specific skin lesions are divided into chronic, subacute, and acute types. The representatives of the chronic and acute types are discoid lupus erythematosus (DLE) and butterfly rash, respectively. Based on the systemic manifestations, we can classify LE into cutaneous-limited LE and systemic LE (SLE). Chronic LE eruptions tend to be seen in cutaneous-limited LE, and acute LE eruptions mainly appear in SLE. Some skin lesions are related to the neurological manifestations of SLE.


Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico/patologia , Humanos , Pele/patologia
10.
Orv Hetil ; 160(15): 563-572, 2019 Apr.
Artigo em Húngaro | MEDLINE | ID: mdl-30957538

RESUMO

MicroRNAs (miRNAs) are 18-25 nucleotide long, single stranded, endogenous, non-coding small RNAs playing an important role in regulating gene expression at posttranscriptional level. miRNAs control approximately 90% of protein-coding genes, and play a central role in various biological processes including immune cell lineage commitment, differentiation, proliferation, apoptosis and maintenance of immune homeostasis. Changes in the expression of certain miRNAs may lead to the development of many diseases, including systemic autoimmune diseases. In this study, we summarize the biogenesis of miRNAs, their role in regulation of the immune system, and review the latest research findings in systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis and systemic sclerosis. In the future, miRNAs may help not only in establishing diagnosis and prognosis but potentially serve as targets for modern therapeutic approaches in autoimmune diseases. Orv Hetil. 2019; 160(15): 563-572.


Assuntos
Artrite Reumatoide/genética , Doenças Autoimunes/genética , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Escleroderma Sistêmico/genética , Síndrome de Sjogren/genética , Artrite Reumatoide/patologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Regulação da Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/patologia , MicroRNAs/imunologia , Escleroderma Sistêmico/patologia , Síndrome de Sjogren/patologia
11.
Arch Immunol Ther Exp (Warsz) ; 67(3): 161-169, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30944972

RESUMO

The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work, SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure correlated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE, particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential influence on disease progression.


Assuntos
Antígeno CD56/metabolismo , Células Matadoras Naturais/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Células T Matadoras Naturais/imunologia , Adolescente , Antígeno CD56/imunologia , Separação Celular/métodos , Criança , Estudos Transversais , Progressão da Doença , Feminino , Citometria de Fluxo/métodos , Humanos , Imunidade Inata , Células Matadoras Naturais/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Masculino , Células T Matadoras Naturais/metabolismo , Índice de Gravidade de Doença
12.
Mediators Inflamm ; 2019: 2473164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944545

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.


Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Adulto , Ligante de CD40/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade
13.
Best Pract Res Clin Haematol ; 32(1): 74-88, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30927978

RESUMO

Autoimmune diseases (ADs) are associated with an increased risk not only of lymphoproliferative disorders but also of myeloid malignancies. The excess risk of myelodysplastic syndromes and/or acute myeloid leukemia is observed across several AD types, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disorders, multiple sclerosis, among others. The risk of developing myeloid neoplasms (MNs) is dependent on several variables, including the specific AD type, chronicity and severity of the AD, type and duration of exposure of disease modifying anti-rheumatic drugs or cytotoxics/immunosuppressives, and genetic predisposition risk. Putative triggering factors linking AD to elevated MN risk include AD-directed medications, shared genetic susceptibilities between the two disease entities, and chronic immune stimulation or bone marrow infiltration by the AD. Molecular mechanisms underpinning leukemogenesis remain largely speculative and warrant further investigation. Leukemias arising in patients with AD are not always 'therapy-related' in that MNs may develop in certain AD subtypes even among patients with no prior therapy exposure. Only a few studies have attempted to determine factors associated with MN development in AD but failed to demonstrate consistent characteristic clinical or paraclinical features. These reports have failed to demonstrate a clear correlation between individual agent exposure and subsequent leukemia development due to the low rates of therapy exposure compounded by the rarity of MN occurrence. Notwithstanding, the leukemogenic potential is best documented with agents such as azathioprine, cyclophosphamide, and mitoxantrone; this risk of MN development does not appear to be shared by biologic approaches such as anti-tumor necrosis factors-alpha inhibitors. In this article, we discuss plausible biologic mechanisms underlying MN pathogenesis in AD and review the data available on the development of MNs in patients with AD.


Assuntos
Artrite Reumatoide , Ciclofosfamida/efeitos adversos , Predisposição Genética para Doença , Imunossupressores/efeitos adversos , Leucemia Mieloide Aguda , Lúpus Eritematoso Sistêmico , Mitoxantrona/efeitos adversos , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Ciclofosfamida/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Mitoxantrona/uso terapêutico , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia
14.
Clin Rheumatol ; 38(5): 1521-1528, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30879204

RESUMO

Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or microtubular structures or both associated with podocytic infolding into the glomerular basement membrane (GBM) on electron microscopy. We present two new cases of PIG with connective tissue disease (CTD), one with primary Sjögren's syndrome and the other with systemic lupus erythematosus (SLE), and make a systemic review of the literature. In the entire 31 patients of PIG, 24 (77.42%) were women and seven (22.58%) were men, with an average age of 41.2 ± 15.2 (ranging from 14 to 79) years old. Almost two-thirds of patients (67.74%) were diagnosed with CTD, in which 76.19% were SLE. All patients presented with proteinuria and six (19.35%) patients were accompanied with hematuria. Serum creatinine was elevated in six (19.35%) patients. Pathological findings of all patients were consistent with PIG characteristics, and four patients with repeated renal biopsies further provided profound insights.


Assuntos
Membrana Basal Glomerular/patologia , Nefropatias/patologia , Lúpus Eritematoso Sistêmico/patologia , Podócitos/patologia , Síndrome de Sjogren/patologia , Adulto , Creatinina/sangue , Feminino , Hematúria/etiologia , Humanos , Proteinúria/etiologia , Adulto Jovem
15.
Lupus ; 28(5): 583-590, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30841789

RESUMO

Musculoskeletal manifestations are extremely common in patients with systemic lupus erythematosus. Transient and migratory arthralgia is frequently reported even without clinical signs of joint or tendon inflammation. In less than 15% of patients, joints may be more severely affected by deforming (Jaccoud's arthropathy) and/or erosive arthropathy (Rhupus syndrome). In recent years, ultrasound has emerged as a promising imaging technique for the assessment of musculoskeletal involvement in systemic lupus erythematosus, having demonstrated the ability to detect inflammation and structural damage both at articular and periarticular level. Recent ultrasound studies have also revealed new insights into musculoskeletal involvement in patients with systemic lupus erythematosus, some of them questioning the traditional concepts of systemic lupus erythematosus arthropathy, with potential clinical, prognostic and therapeutic implications. In daily clinical practice, the use of ultrasound in the assessment of joint and tendon involvement in patients with systemic lupus erythematosus is still limited. Several methodological issues encountered in ultrasound studies evaluating musculoskeletal involvement in systemic lupus erythematosus patients need to be addressed in order to improve both the reliability and clinical usefulness of ultrasound findings. This paper reviews ultrasound studies assessing musculoskeletal involvement in patients with systemic lupus erythematosus, highlighting certainty, limits, potential applications and future perspectives of ultrasound use in systemic lupus erythematosus patients.


Assuntos
Artropatias/patologia , Articulações/patologia , Lúpus Eritematoso Sistêmico/patologia , Sistema Musculoesquelético/fisiopatologia , Tendões/patologia , Humanos , Artropatias/diagnóstico por imagem , Articulações/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Reprodutibilidade dos Testes , Tendões/diagnóstico por imagem , Ultrassonografia
16.
Diagn Cytopathol ; 47(7): 740-742, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30912873

RESUMO

The occurrence of lupus erythematosus cells (LE cells) in serous body fluids is extremely uncommon but, when present, is highly specific for systemic lupus erythematosus (SLE). LE cells are commonly reported in pleural and peritoneal effusions but very rarely documented in pericardial effusion. Here, we report a case in which pericardial fluid examination clinched the diagnosis of SLE which was clinically suspected of tuberculosis/hypothyroid effusion by striking presence of LE cells on May-Grünwald Giemsa-stained and Papanicolaou stained smears. Subsequent serologic studies revealed high titers of anti-nuclear antibodies and anti-ds-DNA confirming the diagnosis of SLE. This case highlights the importance of careful examination of pericardial fluid or pleural or peritoneal fluid in the diagnosis of unsuspected cases of SLE in an era wherein "LE cell detection" is considered to be of historic interest.


Assuntos
Hipotireoidismo/patologia , Lúpus Eritematoso Sistêmico/patologia , Líquido Pericárdico/citologia , Tuberculose/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Teste de Papanicolaou
17.
Internist (Berl) ; 60(5): 468-477, 2019 05.
Artigo em Alemão | MEDLINE | ID: mdl-30840107

RESUMO

Lupus nephritis (LN) is the most frequent and one of the most severe organ manifestations of systemic lupus erythematosus. The central pathogenetic mechanism is characterized by the loss of immune tolerance against autoantigens of the cell nucleus, which can lead to renal inflammation via the formation of nuclear autoantibodies. The clinical manifestations of LN encompass nephritic syndrome with the special form of rapidly progressive glomerulonephritis, nephrotic syndrome and thrombotic microangiopathy. The diagnostic procedures consist of renal function and urine analysis as well as the determination of serum autoantibody profiles and complement components. An early renal biopsy enables a differentiation between the prognostically different forms of LN. In addition to supportive measures, a differentiated immunosuppressive treatment is the main approach for prognostically unfavorable forms. Important components are corticosteroids, cyclophosphamide and mycophenolate mofetil for induction treatment. Currently investigated treatment principles include next generation calcineurin inhibitors and anti-B cell treatment.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Microangiopatias Trombóticas/patologia , Humanos
18.
Nutrients ; 11(3)2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30884776

RESUMO

The prognostic nutritional index (PNI), controlling nutritional status (CONUT) score and nutritional risk index (NRI) have been described as useful screening tools for patient prognosis in several diseases. The aim of this study was to examine the relationship between PNI, CONUT and NRI with clinical disease activity and damage in 173 patients with systemic lupus erythematous (SLE). Disease activity was assessed with the SLE disease activity index (SLEDAI-2K), and disease-related organ damage was assessed using the SLICC/ACR damage index (SDI) damage index. PNI and NRI were significantly lower in active SLE patients than in inactive SLE patients (p < 0.001 and p = 0.012, respectively). PNI was inversely correlated with the SLEDAI score (p < 0.001) and NRI positively correlated with SLEDAI and SDI scores (p = 0.027 and p < 0.001). Linear regression analysis adjusting for age, sex and medications showed that PNI was inversely correlated with SLEDAI (ß (95% CI) = -0.176 (-0.254, -0.098), p < 0.001) and NRI positively correlated with SLEDAI (ß (95% CI) = 0.056 (0.019, 0.093), p = 0.003) and SDI (ß (95% CI) = 0.047 (0.031, 0.063), p < 0.001). PNI (odds ratio (OR) 0.884, 95% confidence interval (CI) 0.809⁻0.967, p = 0.007) and NRI ((OR) 1.067, 95% CI 1.028⁻1.108, p = 0.001) were independent predictors of active SLE. These findings suggest that PNI and NRI may be useful markers to identify active SLE in clinical practice.


Assuntos
Progressão da Doença , Lúpus Eritematoso Sistêmico/sangue , Avaliação Nutricional , Estado Nutricional , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Int J Mol Sci ; 20(6)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889825

RESUMO

Dysfunction of FcGRIIb, the only inhibitory receptor of the FcGR family, is commonly found in the Asian population and is possibly responsible for the extreme endotoxin exhaustion in lupus. Here, the mechanisms of prominent endotoxin (LPS) tolerance in FcGRIIb-/- mice were explored on bone marrow-derived macrophages using phosphoproteomic analysis. As such, LPS tolerance decreased several phosphoproteins in the FcGRIIb-/- macrophage, including protein kinase C-ß type II (PRKCB), which was associated with phagocytosis function. Overexpression of PRKCB attenuated LPS tolerance in RAW264.7 cells, supporting the role of this gene in LPS tolerance. In parallel, LPS tolerance in macrophages and in mice was attenuated by phorbol 12-myristate 13-acetate (PMA) administration. This treatment induced several protein kinase C families, including PRKCB. However, PMA attenuated the severity of mice with cecal ligation and puncture on LPS tolerance preconditioning in FcGRIIb-/- but not in wild-type cells. The significant reduction of PRKCB in the FcGRIIb-/- macrophage over wild-type cell possibly induced the more severe LPS-exhaustion and increased the infection susceptibility in FcGRIIb-/- mice. PMA induced PRKCB, improved LPS-tolerance, and attenuated sepsis severity, predominantly in FcGRIIb-/- mice. PRKCB enhancement might be a promising strategy to improve macrophage functions in lupus patients with LPS-tolerance from chronic infection.


Assuntos
Endotoxinas/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Macrófagos/metabolismo , Fosfoproteínas/metabolismo , Proteína Quinase C beta/metabolismo , Proteômica , Receptores de IgG/deficiência , Animais , Citocinas/sangue , Lipopolissacarídeos , Lúpus Eritematoso Sistêmico/sangue , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de IgG/metabolismo , Sepse/sangue , Sepse/patologia , Índice de Gravidade de Doença , Acetato de Tetradecanoilforbol/farmacologia
20.
Lupus ; 28(3): 324-333, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30813872

RESUMO

BACKGROUND: Toll-like receptor (Tlr) 9 is capable of recognizing exogenous and/or endogenous nucleic acids and plays a crucial role in innate and adaptive immunity. Recently, we showed that Tlr9 is overexpressed in podocytes, a component of the blood-urine barrier (BUB), in glomeruli of autoimmune glomerulonephritis (AGN) model mice. This study investigated the activation of peritubular capillary (PTC) endothelial cells (ECs), a component of the BUB in the tubulointerstitium, through overexpressing Tlr9, and the subsequent development of tubulointerstitial lesions (TILs) in AGN model mice. METHODS: Lupus-prone BXSB/MpJ-Yaa (Yaa) and BXSB/MpJ (BXSB) mice were used as an AGN model and control, respectively. In addition to histopathological and ultrastructural techniques, protein and mRNA levels were also evaluated. The relationship between Tlr9 and TIL indices was analyzed by statistical correlation analysis. RESULTS: Yaa mice developed TILs and showed strong Tlr9 mRNA expression in PTC ECs at 24 weeks (wks) of age. However, BXSB mice showed no TIL but faint expression of Tlr9 mRNA at 8 and 24 wks of age. Tlr9 protein localization on PTC was almost absent in BXSB mice at both ages but intense expression was found in Yaa mice only at 24 wks of age. Relative mRNA expression of Tlr9 and its putative downstream cytokines, including interleukin 1 beta ( Il1b), Il6, interferon gamma ( Ifng), and tumor necrosis factor alpha ( Tnf) was markedly increased in isolated tubulointerstitium from Yaa mice at 24 wks of age. Furthermore, electron microscopy examination revealed PTC injury and TIL in Yaa mice at 24 wks. The expression level of Tlr9 in the tubulointerstitium was correlated with inflammatory cells in TILs, injured PTC, Ilb and Tnf expression, and damaged tubules ( P < 0.05 and 0.01). CONCLUSION: Induced expression of Tlr9 in ECs correlates with PTC injury and the development of TILs in lupus-prone AGN model mice.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Nefrite Intersticial/genética , Receptor Toll-Like 9 , Animais , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Expressão Gênica , Humanos , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Nefrite Intersticial/patologia , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas
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