RESUMEN
INTRODUCTION AND HYPOTHESIS: The classic triad of dry eyes, mouth and vagina is known to most gynaecologists as pathognomonic of Sjögren's syndrome, but rheumatologists seldom consider vaginal symptoms. Our hypothesis was that women with Sjögren's syndrome would have an increased likelihood of postoperative voiding dysfunction, severe vaginal stenosis or poor response to anticholinergics compared with the general urogynaecology patient. METHODS: All patients with Sjögren's syndrome were prospectively recorded from July 2007 to June 2015. Presenting complaint, pelvic examination findings, previous/subsequent pelvic surgery, voiding dysfunction and response to anticholinergics were noted. The denominator, all new urogynaecology patients, was prospectively recorded. RESULTS: Fifteen patients were identified over 8 years (0.5 % of 2794 new presentations). Of the seven patients who had previously undergone surgery elsewhere, all had demonstrable pelvic tissue fibrosis; five had such severe fibrosis that no speculum could be passed. Anticholinergic medications were completely intolerable in 10/11 (91 %) women, and severe postoperative voiding dysfunction occurred in 6/9 (67 %) women. Only 2/15 (13 %) women were unaffected by fibrosis, postoperative voiding dysfunction or intolerance to anticholinergics. CONCLUSIONS: This audit demonstrates a substantial risk of vaginal stenosis, postoperative voiding dysfunction or severe intolerance to anticholinergics in women with Sjögren's syndrome.
Asunto(s)
Trastornos del Suelo Pélvico/etiología , Diafragma Pélvico/cirugía , Complicaciones Posoperatorias/etiología , Síndrome de Sjögren/complicaciones , Anciano , Antagonistas Colinérgicos/efectos adversos , Constricción Patológica/etiología , Tolerancia a Medicamentos , Femenino , Humanos , Auditoría Médica , Persona de Mediana Edad , Diafragma Pélvico/fisiopatología , Trastornos del Suelo Pélvico/terapia , Estudios Prospectivos , Factores de Riesgo , Síndrome de Sjögren/fisiopatología , Trastornos Urinarios/etiología , Vagina/cirugíaRESUMEN
OBJECTIVE: Beta-2-glycoprotein I (ß2 GPI) constitutes the major autoantigen in the antiphospholipid syndrome (APS), a common acquired cause of arterial and venous thrombosis. We recently described the novel observation that ß2 GPI may exist in healthy individuals in a free thiol (biochemically reduced) form. The present study was undertaken to quantify the levels of total, reduced, and posttranslationally modified oxidized ß2 GPI in APS patients compared to various control groups. METHODS: In a retrospective multicenter analysis, the proportion of ß2 GPI with free thiols in serum from healthy volunteers was quantified. Assays for measurement of reduced as well as total circulating ß2 GPI were developed and tested in the following groups: APS (with thrombosis) (n=139), autoimmune disease with or without persistent antiphospholipid antibodies (aPL) but without APS (n=188), vascular thrombosis without APS or aPL (n=38), and healthy volunteers (n=91). RESULTS: Total ß2 GPI was significantly elevated in patients with APS (median 216.2 µg/ml [interquartile range 173.3-263.8]) as compared to healthy subjects (median 178.4 µg/ml [interquartile range 149.4-227.5] [P<0.0002]) or control patients with autoimmune disease or vascular thrombosis (both P<0.0001). The proportion of total ß2 GPI in an oxidized form (i.e., lacking free thiols) was significantly greater in the APS group than in each of the 3 control groups (all P<0.0001). CONCLUSION: This large retrospective multicenter study shows that posttranslational modification of ß2 GPI via thiol-exchange reactions is a highly specific phenomenon in the setting of APS thrombosis. Quantification of posttranslational modifications of ß2 GPI in conjunction with standard laboratory tests for APS may offer the potential to more accurately predict the risk of occurrence of a thrombotic event in the setting of APS.
Asunto(s)
Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Trombosis/etiología , beta 2 Glicoproteína I/sangre , beta 2 Glicoproteína I/inmunología , Adulto , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombosis/sangre , Trombosis/inmunologíaRESUMEN
Early diagnosis and treatment of rheumatoid arthritis (RA) is necessary to prevent joint damage and long-term disability. High rates of false-negative and false-positive results of the rheumatoid factor (RF) test make it generally unhelpful in the early diagnosis of RA. A new clinical test for RA--the anti-citrullinated peptide antibody (ACPA) test--is now widely available in Australia. Owing to its high specificity (95%), a positive ACPA test result usually confirms a diagnosis of RA in a patient with undifferentiated inflammatory arthritis. The superior specificity of the ACPA test provides an argument for it to replace the RF test in the primary care setting. Performing both tests adds little to the use of the ACPA test alone. An early diagnostic opinion from a rheumatologist is still recommended, as the ACPA and RF tests frequently return negative results in early RA.
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Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Humanos , Sensibilidad y EspecificidadRESUMEN
Serum protein oxidation levels in people with the autoimmune disease systemic lupus erythematosus (SLE) have previously been shown to (a) be elevated at a single time point and (b) correlate with disease activity. This study investigates whether this elevation is a chronic phenomenon, by analysis of multiple serum samples collected from 21 SLE patients and nine controls over a period of up to 38 months. Protein thiols were chronically decreased in SLE patients with stable or variable disease activity compared to controls, whilst protein-bound carbonyls and glycine were chronically increased. 2D-gel analysis of carbonyl distribution showed albumin and immunoglobulins to be particularly affected. In SLE patients with stable disease activity, higher long-term protein oxidation correlated with higher long-term disease activity. SLE patients with variable disease activity exhibited varying correlations between protein oxidation and disease activity markers. These results further support a role for oxidative stress in the pathogenesis of SLE.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Lupus Eritematoso Sistémico/sangre , Adulto , Western Blotting , Estudios de Casos y Controles , Estudios de Cohortes , Progresión de la Enfermedad , Electroforesis en Gel Bidimensional , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo/fisiología , Unión Proteica , Índice de Severidad de la EnfermedadRESUMEN
Increased oxidative stress is a hallmark of the autoimmune disease systemic lupus erythematosus (SLE). This study compares serum protein oxidation levels in SLE patients without and with renal involvement (lupus nephritis); the latter have a significantly poorer prognosis. Similar increases in protein carbonyls and decreases in protein thiols were observed in both SLE groups compared to controls. Protein carbonyl distribution, determined by Western blotting of 2D gels, was similar in both SLE groups, suggesting factors other than oxidation also play a role in SLE complications. 2D electrophoresis examined the serum proteome further. Six proteins were significantly decreases in non-renal SLE patients compared to controls; five were identified by mass spectrometry, including one isoform of pro-atherogenic apoCIII. Total apoCIII levels (assessed by ELISA) in lupus nephritis patients were significantly elevated compared to controls or non-renal SLE patients. Thus, levels of oxidized proteins and apoCIII may be useful biomarkers in SLE studies.
Asunto(s)
Apolipoproteína C-III/sangre , Proteínas Sanguíneas/metabolismo , Lupus Eritematoso Sistémico/sangre , Nefritis/sangre , Adulto , Apolipoproteína C-III/aislamiento & purificación , Biomarcadores/sangre , Proteínas Sanguíneas/aislamiento & purificación , Electroforesis en Gel Bidimensional , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lupus Eritematoso Sistémico/clasificación , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Nefritis/etiología , Oxidación-Reducción , ProteomaRESUMEN
OBJECTIVE: To examine protein oxidation in systemic lupus erythematosus (SLE) and to correlate levels of protein oxidation products with disease activity. METHODS: Serum was collected from SLE patients and healthy control subjects. Protein-bound carbonyls and the pro-oxidant enzyme myeloperoxidase (MPO) were quantified by enzyme-linked immunosorbent assay. Protein thiols were quantified using 5,5'-dithionitrobenzoic acid. Protein-bound amino acids and methionine, tyrosine, and phenylalanine oxidation products were quantified by acid hydrolysis and high-performance liquid chromatography. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Levels of anti-double-stranded DNA (anti-dsDNA) antibodies were measured by radioimmunoassay. RESULTS: Compared with control subjects, SLE patients exhibited elevated levels of protein carbonyls (0.108 +/- 0.078 versus 0.064 +/- 0.028 nmoles/mg of protein; P = 0.046), decreased levels of protein thiols (3.9 +/- 1.1 versus 4.9 +/- 0.7 nmoles/mg of protein; P = 0.003), decreased levels of protein-bound methionine (P = 0.0007), and increased levels of protein-bound methionine sulfoxide (P = 0.0043) and 3-nitrotyrosine (P = 0.0477). SLE patients with high SLEDAI scores or elevated anti-dsDNA antibody levels exhibited increased oxidation compared with patients with low SLEDAI scores or low antibody levels. Serum MPO levels were decreased in SLE patients (P = 0.03), suggesting that this enzyme is not responsible for the enhanced protein oxidation. CONCLUSION: We found elevated levels of multiple markers of protein oxidation in sera from SLE patients compared with controls, and these levels correlated with disease activity. The findings suggest that protein oxidation may play a role in the pathogenesis of chronic organ damage in SLE.