Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits.

Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1-/- ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking ß1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating ß1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+ dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+ regulatory T cells (Tregs), and increased number of CD8+ T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+ T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.

Primary Sjögren's syndrome and pregnancy: A report of 18 cases. / Síndrome de Sjögren primario y embarazo: reporte de 18 casos.

Primary Sjögren's syndrome (pSS) is a condition that predominantly affects women. Reports of pregnancy outcome in these patients are limited and contradictory. OBJECTIVE: To describe pregnancy characteristics and outcomes and newborn morbidity in women with pSS. MATERIAL AND METHODS: We included women with pSS who became pregnant after the onset of the symptoms of the disease. Clinical and serological characteristics, risk factors and previous maternal comorbidities are described. For each pregnancy in a woman with pSS, we recorded pregnancy course and outcome and newborn condition. RESULTS: We assessed 11 patients with 18 pregnancies after the onset of pSS symptoms. All of them presented FAN +; 10 anti-Ro / SSA + and 7 anti-La / SSB +. The mean age in years at the onset of symptoms was 24.9 (SD 6.9) and at the time of pregnancy was 30.3 (SD 5.4). Thirteen pregnancies happened before the diagnosis, reporting only one miscarriage. Two preterm births, 1 case of oligohydramnios, 2 of premature membrane rupture and 2 low birthweight babies were reported after the onset of pSS symptoms. There was 1 newborn with congenital atrioventricular block and another with neonatal cutaneous lupus. All the women with pregnancy complications (n=6) had anti-Ro/SSA antibodies. CONCLUSIONS: Almost half of the pregnancies assessed in women with pSS were associated with complications not attributable to factors other than the disease.

Xerostomía en pacientes con fibromialgia: Estudio epidemiológico / Xerostomia in fibromyalgia patients: Epidemiologic study

Introducción: Dentro de los fenómenos clínicos estudiados asociados a la Fibromialgia (FM) se ha descrito el Síndrome Sicca, cuyo término engloba xeroftalmia, xerostomía, xerodermia y xerovagina. El objetivo de este estudio fue estimar la frecuencia de xerostomía en pacientes con diagnóstico de fibromialgia y describir las características clínicas de dichos pacientes. Material y métodos: Se incluyeron pacientes con diagnóstico de FM según criterios ACR 1990 y 2010, en quienes se evalúo la presencia de xerostomía mediante las preguntas correspondientes al dominio de los criterios clasificatorios 2002 ACR-EULAR de Sjögren y se realizó sialometría no estimulada para medición de flujo salival. Resultados: Se reclutaron 50 pacientes, el 100% fueron mujeres. La media de edad fue 47 años (DS+-8,5), siendo la media tiempo de evolución de la FM de 6 años (DS+-4,5). En total 29 pacientes (51%) refirieron xerostomía y de este grupo sólo 4 sialometrías fueron positivas. El tabaquismo fue más prevalente en las pacientes con FM que no referían xerostomía con respecto a las que sí referían xerostomía (31,8 % vs 6,9%, p 0,02), sin encontrarse diferencias estadísticamente significativas en las características clínicas evaluadas. Conclusión: La prevalencia de xerostomía fue del 51%. No se demostró una disminución del flujo salival objetiva en la mayoría de los pacientes con FM.

Introduction: The aim of this study was to determinate the frecuency of xerostomia in patients with diagnosis of Fibromyalgia (FM) and describe their clinical characteristics. Material and methods: Patients were included according 1990 and 2010 ACR Classification criteria. All of them were evaluated for xerostomia and a sialometry was performed in order to determinate the decrease of salival flow. Results: Fifty patients were recruited during the study. The 100% of them were women. The mean age was 47 years old (DS+-8.5), while the mean time of evolution of FM was 6 years (SD +-4.5). Twenty nine patients reported xerostomia of which 4 presented positive sialometry. Smoking was more prevalent in patients with FM who did not report xerostomia with respect of those who reported xerostomia (31.8% vs 6.9%, p 0.02). Conclusion: The frequency of xerostomia was 51%. No statistically significant associations were found in patients who reported xerostomia. A decrease in objective salivary flow was not demonstrated in patients with FM.

Manifestaciones cutáneas extraglandulares en pacientes con síndrome de Sjögren primario / Extraglandular cutaneous manifestations in patients with primary Sjögren's syndrome

RESUMEN Objetivos: Describir la frecuencia de manifestaciones cutáneas extraglandulares en pacientes con síndrome de Sjögren primario. Determinar el perfil clínico y de laboratorio de los pacientes que presentan estas manifestaciones en comparación con aquellos que no las presentan. Materiales y métodos: Se analizaron los datos de los pacientes incluidos en la base GESSAR (Grupo de Estudio Síndrome de Sjögren de la Sociedad Argentina de Reumatología). Para la comparación entre grupos, los controles se seleccionaron en forma aleatoria con una relación casos: controles de 1:4. A su vez, se compararon los pacientes con púrpura con los controles. Resultados: Sesenta y siete (14,1%) de los 474 pacientes incluidos en la base de datos tuvieron manifestaciones cutáneas extraglandulares. De ellos, el 58% tuvo púrpura. La artritis, la neuropatía, el descenso de C3 y de C4, y la crioglobulinemia fueron estadísticamente más frecuentes en los casos en comparación con los controles; sin embargo, no se encontró asociación independiente con ninguna de estas variables. En lo que respecta a púrpura, la artritis, la neuropatía periférica, la anemia, el descenso de C3 y de C4, anti-La y crioglobulinemia fueron estadísticamente más frecuentes en comparación con los controles. Solo el descenso de C4 y la positividad de crioglobulinas se asociaron en forma independiente a la presencia de púrpura. Conclusión: El 14% de los pacientes presentaron manifestaciones cutáneas extraglandulares. La púrpura fue la manifestación más frecuente. Esta se asoció en forma independiente con el descenso de C4 y la presencia de crioglobulinas.

ABSTRACT Objectives: To describe the frequency of extra-glandular cutaneous manifestations in patients with primary Sjögren's syndrome. To determine the clinical and laboratory profile of patients who present with these manifestations compared to those who do not. Materials and methods: A study was made of patients included in GESSAR database (Sjögren Syndrome Society of Argentina Rheumatology Study Group) were analyzed. For the comparison between groups, the controls were randomly selected, with a case:control ratio of 1:4. Patients with purpura were compared with controls. Results: A total of 67 (14.1%) of the 474 patients included in the database had extra-glandular cutaneous manifestations. Of them, 58% had purpura. Arthritis, neuropathy, a decrease in C3 and C4 levels, and the presence of cryoglobulins, were statistically more frequent in cases compared to controls, although there was no independent association found with any of these variables. As regards purpura, arthritis, peripheral neuropathy, anaemia, decrease in C3 and C4, anti-La, and cryoglobulinemia were statistically more frequent compared to controls. Only the decrease in C4, and the presence of cryoglobulins were independently associated with the presence of purpura. Conclusion: Extra-glandular cutaneous manifestations were observed in 14% of the patients. Purpura was the most frequent cutaneous manifestation. This was independently associated with decreased C4 and the presence of cryoglobulins.