RESUMO
Pemphigus vulgaris (PV) is a chronic autoimmune disorder with potentially fatal outcomes. The aim of this study was to investigate the effect of l-carnitine (LC) on secreted frizzled-related protein-5 (SFRP5), omentin, visfatin, and glycemic indices in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with PV were divided randomly into two groups to receive 2 g of LC or a placebo for 8 weeks. Serum levels of SFRP5, omentin, visfatin, and also glycemic indices were evaluated at the baseline and end of the study. LC supplementation significantly decreased the serum level of visfatin (95% CI [-14.718, -0.877], p = .05) and increased the serum levels of SFRP5 (95%CI [1.637, 11.380], p < .006) and omentin (95% CI [9.014, 65.286], p < .01). However, LC supplementation had no significant effects on the serum levels of glycemic factors such as insulin (95% CI [-1.125, 3.056], p = .426), fasting blood sugar (95% CI [-4.743, 3.642], p = .894), homeostatic model assessment of insulin resistance (95% CI [-0.305, 0.528], p = .729), and quantitative insulin-sensitivity check index (95% CI [-0.016, -0.010], p = .81). LC supplementation decreased visfatin serum level and increased omentin-1 and SFRP5 serum levels in patients with PV. However, it has no significant effect on the serum levels of insulin and glycemic indices.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Glicemia/efeitos dos fármacos , Carnitina/farmacologia , Citocinas/sangue , Lectinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pênfigo/tratamento farmacológico , Adulto , Idoso , Glicemia/metabolismo , Carnitina/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Proteínas Ligadas por GPI/sangue , Indicadores Básicos de Saúde , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Pênfigo/sangue , Pênfigo/metabolismo , PlacebosRESUMO
BACKGROUND: Drug-induced pemphigus is mainly caused by drugs containing sulfhydryl (thiol) groups in their molecules. OBJECTIVES: To understand the serial alteration of anti-desmoglein (Dsg) antibody profile in patients with rheumatoid arthritis (RA) receiving thiol compounds. METHODS: Anti-Dsg1 or -Dsg3 antibodies were analysed twice in a 1.6-year interval, in the same series of RA patients. RESULTS: Eleven of 204 serum samples (5.4%) and 6 of 139 samples (4.3%) from the same RA group showed a positive reaction against Dsg1 or Dsg3 in the first and second screening tests, respectively. The positive rates were higher than those in patients with collagen diseases including systemic lupus erythematosus, Sjögren syndrome, mixed connective tissue disease, and systemic sclerosis. In comparison with the results in the first and second screening tests, one RA patient newly gained anti-Dsg3 antibody, and at least 4 patients lost the antibodies in 1.6 years. Three patients produced antibodies to Dsg1 and/or Dsg3 in a similar fashion as did in the first screening tests. Only one RA serum sample exhibited an intercellular reactivity to human skin or monkey esophagus by immunofluorescence, and another sample bound to a 130 kDa protein suggestive of Dsg3 by immunoblotting. Most anti-Dsg antibodies in RA patients recognized EDTA-resistant epitopes of Dsg different from EDTA-sensitive epitopes recognized by pemphigus sera. CONCLUSION: RA patients receiving any of the thiol compounds may gain autoantibodies to non-conformational epitopes of either Dsg1 or Dsg3, and that such autoantibodies alone are not capable of inducing acantholysis.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Autoanticorpos/sangue , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Compostos de Sulfidrila/uso terapêutico , Acantólise/sangue , Acantólise/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/sangue , Doença Mista do Tecido Conjuntivo/imunologia , Pênfigo/sangue , Pênfigo/etiologia , Pênfigo/imunologia , Polimiosite/sangue , Polimiosite/imunologia , Estudos Prospectivos , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/imunologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/imunologia , Compostos de Sulfidrila/efeitos adversos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Intravenous immunoglobulin (IVIg) is a solution of globulins containing antibodies derived from pooled human plasma of donors and used in the treatment of a number of immune deficiencies and autoimmune diseases. However, several investigators have reported biochemical alterations with use of IVIg. The objective of this study was to evaluate the effects of IVIg therapy on selected biochemical and hematologic parameters in patients with autoimmune mucocutaneous blistering diseases (AMBDs). METHODS: In this preliminary clinical study, ten patients with AMBDs (seven with pemphigus vulgaris and three with mucous membrane pemphigoid) received 133 cycles of IVIg for a total of 399 infusions. We evaluated the effects of IVIg therapy on serum hemoglobin (Hb), albumin, and electrolyte levels, including sodium (Na+), potassium (K+), chloride (Cl-) and calcium (Ca2+). Values of these parameters were measured 24 hours before, during, and 24 hours and 4 weeks after the 3-day infusion period. RESULTS: The observed variations in serum electrolyte levels were physiologically and clinically negligible. Furthermore, 24 hours after the last infusion, mean electrolyte values had spontaneously returned to normal levels without the need for additional supplementation: Na+ 137.59+/-1.42 mmol/L (p=0.6091 vs baseline); K+ 3.97+/-0.5 mmol/L (p=0.2689); Cl- 103.4+/-2.69 mmol/L (p=0.0388); and Ca2+ 9.07+/-0.44 mg/dL (p=0.5332). Conversely, significant variations in mean Hb and albumin levels were observed. When measured 24 hours after the last infusion, mild/moderate decreases in Hb (11.62+/-2.12 g/dL; p=0.009 vs baseline) and/or albumin (mean 3.14+/-0.24 g/dL; p=0.0016 vs baseline) were evident. Such changes may, albeit very rarely, be of sufficient clinical significance in individual patients as to necessitate additional treatment. CONCLUSION: In patients receiving intravenous IVIg for AMBDs, electrolyte values should be monitored but do not represent a real clinical threat. Hemoglobin and albumin values may be altered sufficiently to require additional treatment but this is a very rare occurrence. These findings confirm and extend previous reports of the safety of IVIg therapy.
Assuntos
Albuminas/efeitos dos fármacos , Eletrólitos/sangue , Hemoglobinas/efeitos dos fármacos , Imunoglobulinas Intravenosas/farmacologia , Fatores Imunológicos/farmacologia , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Pênfigo/tratamento farmacológico , Adulto , Idoso , Albuminas/análise , Monitoramento de Medicamentos , Feminino , Hemoglobinas/análise , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Penfigoide Mucomembranoso Benigno/sangue , Pênfigo/sangue , Medição de RiscoRESUMO
BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5.5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 +/- 3.1 pg/ml, P < 0.001), EOLP (3.4 +/- 3.2 pg/ml, P < 0.001), major type EOLP (4.9 +/- 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 +/- 3.0 pg/ml, P < 0.01), or NEOLP (4.2 +/- 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 +/- 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 +/- 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 +/- 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-6/sangue , Levamisol/uso terapêutico , Líquen Plano Bucal/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astragalus propinquus , Biomarcadores/sangue , Combinação de Medicamentos , Eritema Multiforme/sangue , Feminino , Seguimentos , Humanos , Líquen Plano Bucal/sangue , Líquen Plano Bucal/classificação , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Doenças da Boca/sangue , Mucosa Bucal/lesões , Fibrose Oral Submucosa/sangue , Úlceras Orais/sangue , Pênfigo/sangue , Fitoterapia , Síndrome de Sjogren/sangue , Estatística como AssuntoRESUMO
Pemphigus vulgaris (PV) is mediated by autoantibodies to desmoglein 3, the pemphigus vulgaris antigen (PVA). PVA and an extracellular domain of PVA-Ig fusion protein (PV-Ig) can completely adsorb the blister-causing Abs from PV patient sera, suggesting that the extracellular segment of PVA might be sufficient to induce pathogenic Abs. To test this, we immunized rabbits with either PVA or its extracellular domain (EPVA) expressed in insect cells in our laboratory. When Igs were passively transferred from these rabbits into neonatal mice, anti-PVA, but not the anti-EPVA, induced blisters. To understand the basis for their differential pathogenic effects, we examined the properties of these sera. Both sera showed comparable ELISA titers and indirect immunofluorescence reactivity against monkey esophagus, a source of native PVA. Moreover, EPVA, like PVA adsorbed blister-causing Abs from sera of PV patients and rabbits immunized with PVA. In contrast, when IgG preparations were incubated with fura-2-AM (acetyloxymethyl ester)-loaded human keratinocytes in culture, only IgG from anti-PVA serum induced intracellular calcium mobilization. These data showed that PVA but not EPVA can elicit Abs that induced blisters in neonatal mice and mediate intracellular signaling through calcium mobilization.