Application and evaluation of ultrasonography in early stage of sjogren' s syndrome mice / 中国药理学通报

Aim To evaluate the application of submandibular gland ultrasound in diagnosing mouse model of Sjogren' s syndrome (SS). Methods SS model was established in C57BL/6 female mice. Hie saliva volume, water intake and body weight of mice were measured on d 0, d 21, d 28 and d 35 after the first immunization respectively, then the index and pathology of submandibular gland were detected on d 35. Meanwhile, ultrasonic examination was performed on the submandibular gland on a Vevo 2100 small animal ultrasound imaging system. The correlations between the ultrasound observations and the clinic manifestations or submandibular gland histology of SS mouse were analyzed. Results The saliva secretion of SS mice began to decrease significantly on d 28 after modeling, the index of submandibular gland increased significantly on d 35, and the typical pathological changes of SS were observ ed in submandibular gland from model mice. On d 21, it was found that a marked area increment of submandibular gland in axial section of SS mouse compared with that of normal mice. More blood flow signals were detected in submandibular gland of SS mice on d 28 and d 35. Hie analysis showed an evident correlation between the results of ultrasonic observation and the conventional detection indexes. Conclusions Ultrasonography of submandibular gland is able to provide early clues and sensitive semi-quantitative indexes for e-valuating the pathological changes of SS mouse model. It is of great value in dynamically observing the process of SS and thus it is a promising approach for pharmacodynamic studies of anti-SS drugs.

Sjogren' s syndrome with pulmonary bullae in both lungs as lung imaging performance: A case report and literature review / 吉林大学学报(医学版)

Objective: To explore the clinical characteristics of Sjogren' s syndrome (SS) with pulmonary bullae in both lungs as lung imaging performance, to analyze the common lung imaging performance of SS, and to impove the clinicians' understanding of the common lung imaging performace of the SS patients. Methods: The clinical materials, the results of bronchoscope and pathological examination of a SS patient with pulmonary bullae in both lungs as lung imaging performance were collected, and the relative literatures were reviewed. Results: A young female patient with dyspnea and hemoptysis as the chief complaint was permitted to the hospital. The physical examination results showed rampant tooth and there were no other obvious positive signs. The chest CT results showed the pulmonary bullae in both lungs. Further rheumatism examinations, corneal staining, labial gland biopsy and other assistant examinations were performed, and the patient received the related treatment. The serum immunological results indicated anti-SSA, anti-SSB, and corneal staining (+), and the rheumatoid factors were all positive; the pathology of the lower labial gland biopsy showed the number of lymphocytes in each lesion 50; the patient was diagnosed as SS finally. The patient was treated with glucocorticoids and cyclophosphamide. After the treatment, the symptoms of the patient were improved. After discharged from the hospital, the patient was treated with glucocorticoids and cyclophosphamide continuously for 2 months. However, reviewing of chest CT showed no significant changes in the lung bullae in both lungs. Conclusion: SS is a connective tissue disease with diverse clinical manifestations. When the lungs are involved, the lung imaging performance also presents no specificity. When the patient' s chest CT indicates the presence of multiple pulmonary bullae in both lungs, and no causes are find out, the possibility of SS should be considered; so that early detection and early treatment should be performed, and misdiagnosis and delay treatment of illness can be avoided.

Características salivales y estado sistémico de sujetos con xerostomía / Salivary characteristics and systemic status of subjects with xerostomia

RESUMEN: Xerostomía o sensación de boca es una afección que afecta severamente la calidad de vida de quienes la padecen. Si bien se relaciona con la reducción del flujo salival (hiposalivación), existe evidencia contradictoria y se sugiere evaluar características cualitativas salivales y estado sistémico de los afectados para comprender su etiología y mejorar terapias asociadas. El objetivo de este estudio fue comparar pH y concentración de proteínas en saliva y estado sistémico entre sujetos xerostómicos con y sin hiposialia. Se midió pH, concentración de proteínas salivales y se consignaron antecedentes sistémicos y uso de fármacos en 27 individuos xerostómicos, que fueron divididos en hiposiálicos y no hiposiálicos. Se compararon las variables mencionadas usando test no paramétrico de Mann-Whitney y test Chi-Cuadrado. Se aceptaron diferencias estadísticamente significativas con error alfa igual o menor a 5 %. Sujetos xerostómicos con hiposialia presentaron mayor prevalencia de Artritis Reumatoide y Síndrome de Sjögren en comparación con xerostómicos sin hiposialia. No se encontraron diferencias estadísticamente significativas en relación a pH, concentración de proteínas y uso de medicamentos, variables que no influirían en el padecimiento de xerostomía, independiente de la existencia de hiposialia. Sujetos con xerostomía e hiposialia presentan mayor frecuencia de Artritis Reumatoide y Síndrome de Sjögren.

ABSTRACT: Xerostomia or mouth feeling is a condition that severely affects the quality of life of thosewho suffer from it. Although it is related to the reduction of salivary flow (hyposalivation),there is contradictory evidence and it is suggested to evaluate qualitative salivarycharacteristics and systemic state of those affected in order to understand its etiology and improve associated terapies. The objective of this study was to compare saliva, pH and protein concentration and systemic status among xerostomic subjects with and without hyposialia. Were measured PH and protein concentration and were recorded systemic antecedents and drug use in 27 xerostomic individuals, who were divided into hyposalic and nonhyposalic individuals. The mentioned variables were compared using non-parametric Mann-Whitney test and Chi-Square test. Statistically significant differences were accepted with alpha error equal to or less than 0.05%. Xerostomic subjects with hyposialia presented higher prevalence of Rheumatoid Arthritis and Sjögren's Syndrome compared to xerostomics without hyposialia. No statistically significant differences were found in relation to pH, protein concentration and drug use, variables that would not influence xerostomia, independent of hyposialia. Subjects with xerostomia with hyposialia present a higher frequency of Rheumatoid Arthritis and Sjögren's Syndrome.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Posible asociación autoinmune entre síndrome de Laugier-Hunziker y síndrome de Sjögren: reporte de un caso y revisión de la literatura / Laugier-Hunziker syndrome in a patient with Sjögren’s syndrome: report of one case

Laugier-Hunziker syndrome is a rare benign idiopathic condition characterized by acquired macular pigmentation of lips and buccal mucosa, often accompanied with melanonychia. The main concern with this condition is to rule out other differential diagnosis with systemic repercussions and similar hyperpigmentation patterns, such as Peutz-Jeghers syndrome, adrenal insufficiency and melanoma. We report a 58-year-old female with a 20-year history of Sjögren’s syndrome, presenting with melanonychia and hyperpigmentation in the buccal mucosa. She had no relevant medication history and is a non-smoker. The patient denied any other symptoms. The histopathology confirmed the diagnosis of Laugier-Hunziker syndrome.

A case of primary sjogren`s syndrome with distal renal tubular acidosis presenting as hypokalemic paralysis.

Renal tubular acidosis secondary to autoimmune interstitial nephritis is quite common in patients with Sjogren`s syndrome. Here we present a case of 24 year old female who presented with Acute Hypokalemic Quadriparesis and was later diagnosed with distal RTA. Patient did not have features of xerostomia or xerophthalmia but was diagnosed to have Primary Sjogren`s syndrome fromserological findings,in this case renal involvement preceded subjective Sicca syndrome.Patient recovered after giving i.v potassium. Patient was treated with corticosteroids and is asymptomatic during the one year follow up period.

Dental perspective on Sjõgren’s syndrome: literature review / Perspectiva odontológica del síndrome de Sjõgren: revisión de literatura

The human body releases around 500-600mL of saliva daily, however when values of unstimulated whole saliva range from 0.1 to 0.2mL/ min, there is a condition called Hyposalivation or hyposialia. Hyposalia is characterized by a large number of systemic conditions, including Sjõgren’s syndrome, a chronic autoimmune disease that affects between 0.1 and 3 percent of the world population and is characterized by exocrinopathy of the salivary glands leading to glandular hypofunction and thus decreasing the normal salivary flow. Saliva is part of innate immunity, when there is a decrease in protein secretion, numerous oral manifestations occur such as dental caries, candidiasis, gingival disease, angular cheilitis, lymphomas of the salivary glands, dysphagia, erythematous and fissured tongue, among others. Currently there is no defined dental treatment, however there are alternative treatments by sialogogues and salivary substitutes, plus non-pharmacological therapies, which seek to maintain the ecology and oral conditions stable, in addition to preventive and restorative dental treatment for lesions already established as a consequence of the disease. The aim of this study is to conduct a literature review on the characteristics, classification, oral manifestations and dental management of Sjõgren’s syndrome...

El ser humano secreta alrededor de 500 a 600 mL de saliva diariamente, sin embargo, al encontrarse valoresde 0.1 - 0.2 mL/min de saliva en reposo se presenta una condición llamada hiposalivación o hiposialia, la cual puedeser manifestada por una numerosa cantidad de condiciones sistémicas, entre ellas el síndrome de Sjõgren, la cual es una enfermedad autoinmune crónica presente en entre el 0.1 y3% de la población mundial, y es caracterizada por exocrinopatíade las glándulas salivales conllevando a la hipofunción glandular y disminuyendo así el flujo salival normal.Debido a que la saliva forma parte de la inmunidad innata, al presentarse una disminución en su secreción proteica sedesencadenan numerosas manifestaciones orales, tales comocaries dental, candidiasis, enfermedad gingival, queilitis angular, linfomas de las glándulas salivales, disfagia, lenguaeritematosa y fisurada, entre otras. Actualmente no existe un tratamiento odontológico definido, sin embargo se tienen alternativas de tratamiento mediante fármacos sialogogos ysustitutos salivales, además de terapias no farmacológicas, las cuales intentan mantener la ecología y las condiciones orales estables, además de los tratamientos odontológicos preventivosy restaurativos para lesiones ya establecidas por consecuenciade la enfermedad. El objetivo del presente estudio es realizar una revisión de literatura sobre las características, criterios de clasificación, manifestaciones orales y el manejoodontológico del Síndrome de Sjõgren...

Evaluación ecográfica de la glándula salival desde la perspectiva de reumatología / Evaluation of salivary gland by ultrasound from the perspective of rheumatology

The major salivary glands have multiple functions as wet oral mucosa, facilitate swallowing of food, digestion of carbohydrates, control the bacterial flora of the mouth, promote tooth mineralization and immune function by secretory IgA, which they can be altered by some conditions like autoimmune diseases or tumor. Ultrasound is a useful tool for the study of these glands, with the advantage of being safe, inexpensive, reproducible, noninvasive technique. In this review, we make a description of the anatomy and ultrasound anatomy of the major salivary glands and a brief description of the usefulness of elastography in some pathologies of these glands...

Las glándulas salivales mayores tienen múltiples funciones, como humedecer la mucosa oral, facilitar la deglución de alimentos, digestión de carbohidratos, control sobre la flora bacteriana de la boca, favorecen la mineralización de los dientes así como la función inmunológica por la secreción de IgA, las cuales pueden verse alteradas por la afección de enfermedades autoinmunes o tumorales. La ecografía es una técnica útil para el estudio de estas glándulas, con la ventaja de ser inocua, de bajo costo, reproducible y no invasiva. En esta revisión se hacen una descripción de la anatomía y sonoanatomía de las glándulas salivales mayores y una breve descripción de la utilidad de la elastografía en algunas patologías de estas glándulas...

Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu / Síndrome de Sjögren e espectro da neuromielite óptica coexistem em meio de autoimunidade

The relationship between Sjögren’s syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

A relação entre síndrome de Sjögren (SS) e espectro da neuromielite óptica (ENMO) ainda não é bem compreendida. Relatamos dois pacientes com ambas as condições e revisamos 47 casos que preenchem critérios diagnósticos das duas doenças, descritos em 17 artigos extraídos da PubMed. Dos 44 pacientes cujo gênero foi informado 42 eram mulheres. A idade média ao início das manifestações neurológicas foi 36,2 anos (10-74). O anticorpo anti-AQP4 foi positivo em 32 dos 37 pacientes, em 1 foi “borderline”. Nosso Caso 1 era soronegativo para AQP4-IgG, não tinha autoanticorpos não-órgão específicos, exceto anti-SSB. O Caso 2 era soropositivo para anticorpos anti-AQP4, anti-SSA/SSB, anti-tireoglobulina, e anti-receptor da acetilcolina; apresentava hipotireoidismo, mas não havia evidêncas de miastenia gravis. Nossos casos e outros similares, previamente relatados na literatura, com resposta autoimune heterogênea à aquaporina-4 sugerem que a SS e o ENMO coexistem em meio de autoimunidade não dependente da aquaporina-4.

Síndrome de Sjögren y acidosis tubular renal distal reversible: una mirada a sus manifestaciones renales / Sjögren's syndrome and reversible distal renal tubular acidosis: Renal manifestations

Resumen Presentamos el caso de un paciente masculino con síndrome de Sjögren cuya manifestación clínica inicial fue extraglandular, teniendo el riñón como principal órgano afectado bajo la forma de acidosis tubular renal distal, que lo llevó a nefrocalcinosis como complicación en su evolución natural. Su hallazgo permitió el diagnóstico de esta exocrinopatía autoinmune, lográndose la remisión clínica y estabilización de la función renal con el uso de esteroides.

Abstract We describe a male patient with Sjögren's syndrome, whose initial clinical manifestation was extraglandular. The kidney was the main organ affected in the form of distal renal tubular acidosis that led to nephrocalcinosis as a complication during its natural progression. These findings led to the diagnosis of autoimmune exocrinopathy, with clinical remission and stabilization of renal function being achieved with the use of steroids.

Síndrome de Sjögren: conceitos atuais e manejo das manifestações orais / Sjögren?s syndrome: current concepts and management of its oral manifestations

A síndrome de Sjögren é doença sistêmica autoimunitária, caracterizada por infiltração linfocítica nas glândulas exócrinas. Na cavidade oral, esta síndrome potencialmente desencadeia a destruição de ácinos e ductos de glândulas salivares, ocasiona diminuição da secreção salivar com consequente xerostomia e predispõe o indivíduo à cárie dentale à doença periodontal. Com a dificuldade de diagnóstico e a necessidade de tratamento adequado para o alívio dos sintomas e a melhora do estado bucal do paciente, propõe-se uma revisão dos conceitos atuais e conduta clínica a ser adotada diante das alterações na cavidade oral, abordando-se os mecanismos etiopatogênicos, as características clínicas e histopatológicas, os métodos de diagnóstico e tratamento para doentes com síndrome de Sjögren.

Sjögren?s syndrome is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. In the oral cavity, this syndrome potentially triggers the destruction of acini and ducts of the salivary glands, causing reduction of the salivary secretion with consequent xerostomia, leaving the the individual susceptible to thedental caries and the periodontal disease. Due to difficult diagnosis and the requirement of an adequate treatment aiming at the relief of the symptoms and the improvement of the buccal health of the patient. A review of current concepts and clinical management to be adopted in the face of changes in the oral cavity, to be adopted, approachingthe pathophysiology, the clinical and histopathological features, diagnostic methods and treatment for patients with Sjögren?s syndrome.

Scintigraphy of the salivary gland in patients with Sjõgren's syndrome treated with pilocarpine / Cintigrafia da glândula salivar em pacientes com Síndrome de Sjogren tratados com pilocarpina

OBJECTIVE: This report describes monitoring of salivary glands through scintigraphy in one patientwith SS before and after the administration of 1% pilocarpine. DISCUSSION: Sjõgren’s Syndrome(SS) is an immune-mediated disease that most commonly attacks the exocrine glands. The diagnosisof SS is based on the objective and subjective criteria that confirm the damage or diminished activityof salivary and lachrymal glands, in turn resulting in xerostomia and xerophthalmia. CONCLUSION:Scintigraphy with [99mTc] pertechnetate can be used to assess the progression of disease activity, thelocation affected and severity on the glands involved. Scintigraphy can also be used to assess xerostomiathrough activity time analyses, numeric indices, visual interpretations, and radiopharmaceuticalpercentages retained in the gland.

OBJETIVO: Este relato descreve a monitoração de glândulas salivares por meio de cintigrafia em umpaciente com Síndrome de Sjogren antes e após administração de pilocarpina a 1%. DISCUSSÃO: ASíndrome de Sjogren (SJ) é uma doença imunomediada que mais comumente ataca as glândulas exócrinas. O diagóstico da SJ é baseado em critérios objetivos e subjetivos que confirmam o dano ou atividadediminuída das glândulas salivares e lacrimais, resultando em xerostomia e xeroftalmia. CONCLUSÃO:Cintigrafia com pertecnato [99mTc] pode ser para determinar a progressão da doença, o local afetado ea severidade do envolvimento glandular. A cintigrafia pode também ser usada para avaliar xerostomiapor análises de atividade no tempo, índices numéricos, interpretação visual e porcentagensradiofarmacêuticas retidas na glândula.

Óleo de linhaça no tratamento do olho seco de paciente com síndrome de Sjögren / Flaxseed-Oil in the treatment for a dry-eye Sjögren´s syndrome patient

A Síndrome de Sjögren é uma doença auto-imune crônica que se caracteriza por infiltração linfocítica de glândulas salivares e lacrimais, resultando em xerostomia e ressecamento ocular. A utilização dos ácidos graxos essenciais na apresentação oral, como o óleo de linhaça, pode ser uma alternativa no tratamento de pacientes com deficiência lacrimal. Descreve-se o caso de uma paciente, portadora de Síndrome de Sjögren associada à artrite reumatoide, com sinais e sintomas de olho seco. A paciente foi atendida no Ambulatório de Oftalmologia, do Hospital Universitário/CAS, da Universidade Federal de Juiz de Fora. Foi adotada a administração oral de óleo de linhaça, com melhora dos sintomas. O objetivo do relato do caso é incentivar futuros estudos para melhor esclarecimento sobre o uso do óleo de linhaça no tratamento do olho seco.

Sjögren´s syndrome is a chronic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands leading to xerostomia and ocular dryness. Oral treatment with flaxseed (linseed)-oilcapsules may help to improve lacrimal deficiency. We describe the case of a patient with Sjögren´s syndrome associated with rheumatoid arthritis, seen at the Ophtalmology Division of the Federal University of Juiz de Fora Hospital. The patient, with dry-eye symptoms, was treated with oral flaxseed (linseed)-oil capsules, reducing her surface ocular inflammation and alleviating the symptoms of Keratoconjunctivis sicca. The aim of this study was to report the case and encourage future long term studies to confirm the role of this therapy for Keratoconjunctivis sicca in Sjögren´s syndrome.

Enfermedad autoinmune: perturbación de la conversación entre la célula blanco (epitelial) y la matriz extracelular / Autoimmune disease: impaired cross-talk between epithelial cell and extracellular matrix

Glándulas salivales de pacientes con síndrome de Sjõgren presentan un aumento en la degradación de componentes de la lámina basal (LB, laminina y colágeno IV) y estroma (colágenos I y III y fibronectina). Estos cambios se correlacionan con un desbalance en la expresión y actividad de metaloproteinasas y sus inhibidores titulares (MMP/TIMP) que desorganiza la LB de acinos y ductos. Esta desorganización es concomitante a una sobreexpresión de lamininas -1 y -5 y a la degradación de nidógenos 1 y -2, que tienen como función establecer puentes de conexión entre laminina y colágeno IV. Cambios post-transcripcionales de la integrina alfa 6 beta 4 están correlacionados con una drástica redistribución de beta 4 en acinos con LB desorganizadas. Estos resultados sugieren que alteraciones en la adhesión célula-matriz y en la formación de contactos célula-célula pueden modificar la señalización de la integrina alfa 6 beta 4 induciendo muerte celular cuando hay una severa interrupción de la célula acinar con la LB.

Increased degradation of basal lamina (BL, laminin and type IV collagen) and stroma (type I and III collagens, and fibronectin) proteins have been observed in salivary glands of patients with Sjõgren’s syndrome. Such changes are associated with imbalanced expression and activity of extracellular matrix metalloproteinases and their tissue inhibitors (MMPs/TIMPs), which contribute to disorganization of the parenchyma basal lamina. Disorganization of the basal lamina is paralleled by an overexpression of laminin-1and -5 and the degradation of nidogens 1 and -2: linker proteins that help maintain the integrity of type IV collagen and laminin networks.Additionally, post-transcriptional changes in alpha 6 beta 4 integrin are associated with a dramatic redistribution of beta 4 in acini, particularly where perturbations in BL organization were apparent. These findings are taken to suggest that changes in acinar cell-matrix adhesion and cell-cell contact formation may alter alpha 6beta 4 integrin signaling, triggering cell death only when severe disruption of cell-BL attachment occurs.

Síndrome de Sjögren: relato de caso / Sjögren’s Syndrome: a case report

Objetivos: Apresentação de um caso clínico da Síndrome de Sjögren. Métodos: Pesquisa em artigos especializados e observação clínica de um caso da síndrome. esultados: Observou-se que o conhecimento das características clínico- laboratoriais da síndrome pode auxiliar os Cirurgiões-Dentistas a identificar mais facilmente a afecção, contribuindo para a melhora naqualidade de vida do paciente. Conclusão: Por se tratar de uma síndrome que não é considerada rara, há necessidade da demonstração mais atual de seus aspectos principais.

Objective: Presentation of a clinical case of the Sjögren’s Syndrome. Methods: Research in specialized articles and clinical comment of a case of the syndrome. Results: It was observed that the knowledge of the clinical-laboratory characteristics of the syndrome can assist dentists to identify the affection more easily, contributing for the improvement in the patient’s quality of life.

Analysis of 53 Patients with Sjogren' s Syndrome and Idiopathic Pulmonary Fibrosis / 医学研究杂志

Objective To explore the occurrence, clinical feature and the associatrd factors of Sjogren' s syndrome(SS) complicated with Idiopathic Pulmonary Fibrosis(IPF) to build up knowledge for early diagnosis. Methods The clinical characteristics of 160 cases damitted SS patients collected from January 2002 to August 2008 were retrospectively investigated including RF, chest - X, ESR, blood -gas analysis,pulmonary function tests,chest HRCT,ANA and so on. Results The patients with IPF accounted for 33.12% of total SS patients, including 12 cases of male. These patients presented strongly positive ANA,strongly positive RF etc,especially in the male. Conclusion The occurrence of SS - IP was related to the disease' s activity. FHRCT and pulmonary function test should taken early in order to get early diagnosis and treatment.

Anticuerpos anti-CCP en artritis reumatoidea: relación con características clínicas, citocinas Th1/Th2 y HLA-DRB1 / Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: relation with clinical features, cytokines and HLA-DRB1

En el presente estudio se examinó la especificidad y la sensibilidad de los anticuerpos antipéptidos citrulinados cíclicos (CCP) en pacientes latinoamericanas con artritis reumatoidea (AR), así como su relación con la actividad de la enfermedad, manifestaciones extraarticulares (MEA), síntesis de citocinas (IL-4, IL-10, IL-12, TNF-µ e IFN-gamma ) y factor reumatoideo (FR) IgM e IgA, y con el polimorfismo del HLA-DRB1. Se examinaron 79 pacientes con AR (69 con AR establecida y 10 con AR temprana sin previo tratamiento), 56 pacientes con espondilitis anquilosante (EA), 25 con lupus eritematoso sistémico (LES), 50 con síndrome de Sjögren primario (SSp) y diez individuos sanos. De las 69 pacientes con AR establecida, 36 fueron reevaluadas 2 años después. La actividad de la AR se examinó según los criterios del Colegio Americano de Reumatología. Los anticuerpos anti-CCP2, el FR y los niveles de citocinas se determinaron mediante inmunoensayo, y la genotipificación del HLA se llevó a cabo por reacción en cadena de la polimerasa utilizando mezclas de iniciadores específicos. Los anticuerpos anti-CCP se observaron en 96% de los pacientes con AR en la primera evaluación y en 86% en la segunda ( p=0,12), sin modificación significativa en los valores (131±58,7 vs. 130,6±67,1 UI). Su sensibilidad y especificidad global fue de 94% y 92%, respectivamente, pero cuando sólo se consideraron los niveles altos (>60 UI) fueron de 84% y 95%, respectivamente. La razón de probabilidades (RP) positiva fue de 12 y la RP negativa de 0,06. El valor predictivo (VP) positivo fue de 87% y el VP negativo de 96%. Los anticuerpos anti-CCP se observaron en 12% de los pacientes con LES y con SSp, en 2% de los de EA y en 10% de los controles sanos. En los pacientes con AR no se asociaron con la actividad de la enfermedad, MEA y alelos del HLA-DRB1. Tampoco se observaron correlaciones significativas entre sus valores y los niveles de citocinas. En conclusión, los anticuerpos anti-CCP tienen un interés diagnóstico para la AR en nuestra población, pero su utilidad en el seguimiento clínico es limitada y su síntesis es independiente del HLA-DRB1 y no se correlacionan con niveles de citocinas Th1/Th2.

The specificity and sensitivity of anti-cyclic citrullinated peptide antibodies (anti-CCP) was examined in Latin-American patients with rheumatoid arthritis (RA). The variables considered included: 1) relation with the activity of disease, 2) extra-articular manifestations (EAM), 3) synthesis of cytokines (IL-4, IL-10, IL-12, TNF-alpha , and IFN-gamma ) and IgM and IgA rheumatoid factor (RF), and 4) the association with HLA-DRB1 polymorphism. Seventy-nine RA patients were assessed (69 with established RA, and 10 with recent-onset RA not receiving any treatment), 56 with ankylosing spondylitis (AS), 25 with systemic lupus erythematosus (SLE), 50 with primary Sjögren’s syndrome (pSS), and 10 healthy individuals. Of the 69 patients with established RA, 36 were reexamined 2 years later. The activity of the RA was measured by criteria adopted by the American College of Rheumatology. Anti-CCP2, RF and cytokines levels were determined by ELISA. HLA genotypes were established by first, PCR sequence amplification using sequence-specific primers and then, complete sequencing of the product. Anti-CCP antibodies were observed in 96% of patients with RA during the first evaluation and in 86% at the second evaluation ( p=0.12). No significant change in antibody titre was observed between the two evaluations (131±58.7 and 130.6±67.1 IU, respectively). The overall sensitivity and specificity was 94% and 92%, respectively; however, at titres >60 IU, the values were 84% and 95%, respectively. The anti-CCP likelihood ratio positive test was 12 and the likelihood ratio negative test was 0.06. The positive predictive value was 87%, and the negative predictive value was 96%. Anti-CCP antibodies were observed in 12% of SLE and pSS patients, in 2% of AS patients, and in 10% of healthy controls. In RA patients, these antibodies were not associated with the activity of disease, EAM or HLA-DRB1 alleles; no significant correlation was observed between antibody titre and cytokines level. Although anti-CCP antibodies have potential as a diagnostic tool for RA, they are not useful for monitoring clinical activity or predicting the clinical course of disease. Antibody synthesis is HLA-DRB1 independent and not correlated with Th1/Th2 cytokines.

Polimorfismo del TNF- alfa en autoinmunidad y tuberculosis

El factor de necrosis tumoral alfa (TNF-alfa ) está incriminado tanto en enfermedades autoinmunes como en infecciosas. En el presente estudio se examinó el polimorfismo de la región promotora -308 del gen del TNF-alfa en enfermedades autoinmunes; 091; lupus eritematoso sistémico (LES), artritis reumatoidea (AR), síndrome de Sjögren primario (SSp) 093; ; y en tuberculosis. La genotipificación del polimorfismo -308 del TNF-alfa se realizó en ADN de pacientes con AR (N=165), LES (N=118), SSp (N=67), tuberculosis (N=138) y controles sanos (N=419), mediante reacción en cadena de la polimerasa con polimorfismos en los tamaños de los fragmentos de restricción (PCR-RFLP). El alelo TNF2 se asoció con la AR (OR=1,6; IC95% 1,2-2,3, p=0,008), el LES (OR=2,3; IC95% 1,6-3,3, p<0,0001) y el SSp (OR=2,7; IC95% 1,7-4,1, p<0,0001). El alelo TNF1 se asoció con la tuberculosis (OR=1,9: IC95% 1,2-3,1, p=0,02). La heterocigosis TNF1/TNF2 fue factor de riesgo para AR (OR=1,7; IC95% 1,2-2,6, p=0,01), LES (OR=3; IC95% 2-4,7, p<0,0001) y SSp (OR=3,8; IC95% 2,2-6,5, p<0,0001), mientras que la homocigosis TNF1/TNF1 fue protectora para autoinmunidad (OR<0,6, p<0,01). Por el contrario, el genotipo TNF1/TNF2 fue protector para tuberculosis (OR=0,5; IC95% 0,3-0,9, p=0,02) y la homocigosis TNF1/TNF1 se asoció con susceptibilidad a la misma (OR=2; IC95% 1,2-3,4, p=0,02). Los resultados indican que el alelo TNF2 es un factor común de riesgo para enfermedades autoinmunes reumatológicas pero protector para tuberculosis. Esto sugiere una selección genética en nuestra población.

Polymorphism of TNF - alpha in autoimmunity and tuberculosis Tumor necrosis factor alpha (TNF-alpha ) has been incriminated in several autoimmune and infectious diseases. The influence of TNF-a -308 polymorphism was examined in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS) and tuberculosis. Genomic DNA from patients with RA (N=165), SLE (N=118), pSS (N=67), tuberculosis (N=138), as well as ethnic-matched controls (N=419) were characterized for the TNF-a -308 genetic polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. TNF2 allele was associated with RA (OR: 1.6, C.I.95% 1.2-2.3, p=0.008), SLE (OR: 2.3, 95%C.I. 1.6-3.3, p<0.0001), and pSS (OR: 2.7, 95%C.I. 1.7-4.1, p<0.0001). TNF1 was associated with tuberculosis (OR: 1.9, 95%C.I. 1.2-3.1, p=0.02). TNF1/TNF2 heterozygosity was associated with susceptibility for RA (OR: 1.7, 95%C.I. 1.2-2.6, p=0.01), SLE (OR: 3, 95%C.I. 2-4.7, p<0.0001), and pSS (OR: 3.8, 95%C.I. 2.2-6.5, p<0.0001). The homozygous state TNF1/TNF1 was protective for autoimmunity (OR<0.6, p<0.01). In contrast, the TNF1/TNF2 genotype was a protective factor for tuberculosis (OR 0.5, 95%C.I. 0.3-0.9, p= 0.02) whereas TNF1/TNF1 homozygosity was associated with susceptibility (OR: 2, 95%C.I. 1.2-3.4, p=0.02). These results indicate that TNF2 is a common susceptibility allele for autoimmune rheumatic diseases and a protective one for tuberculosis. In addition, the data point towards a genetic selection in our population that might be maintained through dominant selection (heterozygote advantage) to infection by M. tuberculosis but susceptible to autoimmunity.

A Case of Type I Renal Tubular Acidosis Associated with Graves' Disease and Sjogren' s Syndrome / 대한신장학회잡지

Classic distal renal tubular acidosis(type 1 RTA) is a hypokalemic, hyperchloremic metabolic acidosis due to selective defect in distal acidification. Type 1 RTA may be associated with genetic(usually autosomal dominant) or autoimmune disease, drugs and toxin and various tubulointerstitial diseases. This case report describes a 27 year-old female patient with distal RTA, Sjogren' s syndrome and Graves' disease the first case. She had been suffered from muscle weakness and peripheral numbness and was found to have low serum potassium(1.6mEq/L). She was revealed to have 1) distal RTA by NaHCO3 loading test 2) Sjogren' s syndrome by Schirmer' s test and palate biopsy and 3) Graves' disease by exophthalmometry and autoantibody test, thyroid function test. This is the first case as far as I search that report the association of distal RTA, Sjogren' s syndrome, and Graves' disease caused by autoimmune mechanism.