The evaluation of the Myxovirus Resistance 1 protein in serum and saliva to monitor disease activation in primary Sjögren's syndrome

OBJECTIVE: Primary Sjögren's syndrome (pSjS) is a chronic autoimmune disease that causes dry eye and mouth. No laboratory parameters to monitor the activation of this disease have been identified. Therefore, any possible relationships between salivary and blood myxovirus resistance 1 (MX1) and pSjS must be prospectively studied. METHODS: Thirty female patients with pSjS, 30 women with rheumatoid arthritis (RA) without secondary Sjögren's syndrome (SjS) and 28 healthy control women were enrolled in this investigation. Analyses of MX1 by the enzyme-linked immunosorbent assay (ELISA) method, SS-A (Ro) and SS-B (La) tests by the strip immunoblot method, anti-nuclear antibody (ANA) tests by immunofluorescence and the measurement of serum rheumatoid factor (RF), C3, C4, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were performed. RESULTS: The serum level of MX1 in patients without Raynaud phenomenon was higher than in those with Raynaud phenomenon (p:0.029, p<0.05, statistically significant). There was a statistically significant positive association between hemoglobin levels and MX1 serum levels. No statistically significant association was found among the other parameters. Low MX1 levels were shown to be associated with both a low disease activity score based on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and hydroxychloroquine use in all patients. CONCLUSION: MX1 levels have a considerable impact on the assessment of the disease activity in SjS. We believe that more-comprehensive studies should be performed on patients with pSjS who do not use hydroxychloroquine to prove this relationship and that MX1 levels should be used as a routine marker for the assessment of pSjS disease activity. Further studies are needed to create awareness of the role that MX1 has in the diagnosis of pSjS, which may help to uncover novel pathways for new therapeutic modalities.

Familial autoimmunity and polyautoimmunity in 60 Brazilian Midwest patients with systemic sclerosis / Autoimunidade familial e poliautoimunidade em 60 pacientes portadores de esclerose sistêmica da região Centro-Oeste do Brasil

ABSTRACT Introduction: Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS), as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%), Sjögren's syndrome (38.5%), and inflammatory myopathy (11.5%). The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%), rheumatoid arthritis (22.6%), and SLE (22.6%). The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a continued vigilance and promptly diagnose other possible autoimmune disease in patients, or in their kin.

RESUMO Introdução: A esclerose sistêmica (ES) é uma enfermidade do tecido conjuntivo de etiologia desconhecida, caracterizada pela tríade de injúria vascular, autoimunidade e fibrose tecidual. Sabe-se que uma história familiar positiva representa o maior fator de risco já identificado para o desenvolvimento da ES em um determinado indivíduo. Observação prévia de alta prevalência de poliautoimunidade e de autoimunidade familiar em pacientes com ES reforça a ideia de que fenótipos autoimunes distintos podem dividir variantes comuns de susceptibilidade. Objetivos: Descrever a frequência de autoimunidade familiar e de poliautoimunidade em 60 pacientes com ES da região Centro-Oeste do Brasil, bem como relatar as principais doenças autoimunes observadas nessa associação de comorbidades. Métodos: Estudo transversal com recrutamento de 60 pacientes consecutivos, selecionados no Serviço de Reumatologia do Hospital Universitário da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul (FMUFMS), bem como entrevista de seus parentes, de fevereiro de 2013 a março de 2014. Resultados: Foi encontrada uma frequência de 43,3% de poliautoimunidade e de 51,7% de autoimunidade familiar nos pacientes com ES. Os pacientes com presença de poliautoimunidade e de autoimunidade familiar eram principalmente da forma difusa de ES, porém esse índice não atingiu significância estatística. As doenças autoimunes mais comumente observadas nos pacientes com poliautoimunidade foram: tireoidite de Hashimoto (53,8%), síndrome de Sjögren (38,5%) e miopatia inflamatória (11,5%). As principais doenças autoimunes observadas nos parentes dos pacientes com ES foram: tireoidite de Hashimoto (32,3%), artrite reumatoide (22,6%) e LES (22,6%). A presença de mais de uma enfermidade autoimune em pacientes com ES não se correlacionou com maior gravidade ou atividade da doença. Conclusões: A partir da alta prevalência encontrada de doenças autoimunes coexistentes em pacientes com ES, salientamos a importância do conceito de autoimunidade compartilhada, de forma a promover uma vigilância constante e diagnosticar prontamente uma possível outra doença autoimune nos pacientes ou em seus parentes.

The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjogren's Syndrome

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.

The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjogren's Syndrome

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.

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.

Cardiac Resynchronization Therapy for Left Ventricular Dysfunction Induced by Chronic Right Ventricular Pacing in a Child

Cardiac resynchronization therapy (CRT) has been proven its value in adult patients with congestive heart failure of low ejection fraction and wide QRS duration. Contrast to adult patients, CRT has been rarely applied for young patients. We report on a 9-yr-old boy with progressive left ventricular (LV) dilatation and dysfunction following chronic VVI pacemaker therapy for congenital complete atrioventricular block associated with maternal anti-SSA/Ro and SSB/La antibody. His LV dysfunction was improved after epicardially established CRT.

Serologic activity against HTLV-I in patients with primary sjogren's syndrome in Mashhad, an endemic area

There are accumulating evidences that Human T cell Leukemia Virus type I [HTLV-l] plays a part in the development of Sjogren's Syndrome [SS]. This virus is endemic in some areas of the world. The objective of this study was to estimate the seroprevalence rates of anti-HTLV-l in 55 patients in Mashhad and to determine whether any association between SS patients and HTLV-l could be observed. We recruited 21 patients with primary SS who consecutively attended our Rheumatology Clinic in Ghaem Hospital affiliated to Mashhad University of Medical Sciences in Mashhad, Northeastern Iran during May 1, 2005 to September 30, 2008. Serum samples were screened for HTLV-l, using an enzyme-linked immunosorbent assay [ELISA]. To compare the seroprevalence rates of HTLV-l found in SS patients with those in the community, we used the viral infection rates calculated for the entire population of blood donors in Mashhad by Blood Transfusion Organization. All patients with SS were negative by ELISA versus HTLV-I. This study demonstrates no prevalence of positivity for HTLV-1 in SS patients in Mashhad. These data are against the role of HTLV-I in the development of SS in our region

Mielitis transversa asociada a enfermedades autoinmunes: revisión / Autoimmune diseases associated to transverse myelitis: review

La mielitis transversa (MT), es un proceso inflamatorio que afecta un área restringida del cordón espinal. La presentación, usualmente dramática, con una rápida progresión de los síntomas que involucran las funciones motoras, sensitivas y autonómicas, hace de la MT aguda una emergencia médica. Aunque su asociación con el lupus eritematoso sistémico (LES) y el síndrome de Sjõgren (SS), ha sido reportada como rara, y no existe acuerdo con respecto al tratamiento de estos pacientes, los diferentes autores si enfatizan el hecho que un diagnóstico precoz y tratamiento agresivo, mejoran el pronóstico. En la revisión de la literatura (MEDLINE) se encontró que las principales enfermedades autoinmunes asociadas a la MT aguda son el LES y el SS. Además, se establece que los anticuerpos antifosfolipídicos (aAP) podrían tener un papel etiológico en la MT. Aunque no existen protocolos terapéuticos uniformes para el tratamiento de estos pacientes y el pronóstico, en muchos casos es pobre, ha sido postulado que el tratamiento temprano y agresivo (usualmente con bolos de esteroides y ciclofosfamida) puede ser crucial para una respuesta adecuada.

Transverse myelitis (TM) is an inflammatory process involving restricted areas of the spinal cord. The usually dramatic presentation with rapidly progressive symptoms involving motor, sensory and autonomic functions makes acute TM a medical emergency. Acute TM has been cited as a rare and unusual complication of systemic lupus erythematosus (SLE) and Sjõgren’s syndrome (SS), but early diagnosis and aggressive treatment might improve the prognosis. This review of the literature (MEDLINE), showed that, within autoimmune diseases, acute transverse myelitis is mainly associated with SLE and SS. Previous studies seem to indicate that the presence of antiphospholipid antibodies might play a role in the etiology of TM. Although no uniform therapeutic protocol exists, and the prognosis is usually poor, early aggressive treatment (usually with EV pulses of methylprednisolone and cyclophosphamide) might improve the prognosis.

Pulmonary manifestations of primary sjögren’s syndrome.

Sjögren's syndrome (SS) is a complex autoimmune exocrinopathy with multifactorial pathogenesis and multisystem manifestation. It is called primary Sjögren's syndrome (PSS) when the manifestations are seen without any other co-existent rheumatic diseases. The incidence of respiratory system involvement varies widely in the reported medical literature, partly due to lack of a universal agreement over the diagnostic criteria of the disease and the type of study methods employed. Respiratory system manifestations are protean; upper airway symptoms are very common and so is the complaint of dry cough. The PSS patients may develop interstitial lung diseases (ILDs) such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), lymphocytic interstitial pneumonia (LIP), bronchiolitis obliterans and organising pneumonia (BOOP), etc. They may also develop the whole spectrum of lymphoproliferative disorders of the lung ranging from LIP to follicular bronchiolitis, nodular lymphoid hyperplasia and low-grade lymphomas. Therapeutic options include symptomatic and supportive measures and corticosteroids as the mainstay of the treatment for ILDs occurring in these patients. In recent years, rituximab (anti-CD20) has emerged as a promising treatment for this disease, though data from controlled trials are still lacking. Pulmonary involvement may be a source of significant morbidity in these patients, though only rarely, it is the cause of death.

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.

Immunization of Balb/c mice with modified auto-antigens for induction of autoimmune sialoadenitis

Sjögren's syndrome is an autoimmune disease characterized by sialoadenitis and elevated titers of autoantibodies. To assess whether it is possible to induce inflammatory changes in salivary gland tissues, a series of immunizations in Balb/c mice have been undertaken, using salivary gland extract, modified or not, added to several adjuvants. Mice's humoral immune response to salivary gland antigens was monitored by ELISA. Inflammatory cells infiltrating gland tissue were seen 3 months after immunization with salivary gland extract modified with pepsin (AgGp) and metaperiodate (AgGMp). Although pathological progression was not observed, the histopathological picture was similar to the initial phase of Sjõgren's syndrome. In addition, a monoclonal antibody reactive with 3 gland polypeptides and anhydrase carbonic II was rescued among B cells from immunized mice. Thus, immunizations with modified autoantigens were able to initiate pathological damage to glandular tissue and stimulate the proliferation of auto-reactive B cells.

A Síndrome de Sjögren é uma doença auto-imune caracterizada por desenvolvimento de sialoadenite e títulos elevados de auto-anticorpos. Com o objetivo de induzir alterações inflamatórias no tecido das glândulas salivares foram realizadas várias imunizações em camundongos BALB/c utilizando extratos de glândulas salivares, modificados ou não, em vários adjuvantes. A resposta humoral para antígenos salivares foi monitorada por ELISA. Células inflamatórias infiltrando o tecido glandular foram vistas 3 meses pós-imunização com extrato de glândula salivar modificado com pepsina (AgGp) e metaperiodato (AgGMp). Embora a evolução patológica não tenha sido observada, o quadro histopatológico foi semelhante à fase inicial da Síndrome de Sjõgren. Também foi possível notar, a partir das células B dos animais imunizados, a produção de anticorpos monoclonais reativos com 3 polipeptídeos glandulares e anidrase carbônica II. Assim, a imunização com auto-antígenos glandulares modificados foi capaz de iniciar o processo patológico no tecido glandular e induzir a proliferação de células B produtoras de auto-anticorpos.

Compromiso del sistema nervioso en el síndrome de Sjõgren primario / Nervous system compromise in primary Sjogren's syndrome

Nervous system involvement in Sjõgren's syndrome (SS) is extensive in its clinical expression and can be extremely serious, nevertheless it has been poorly studied. It can involve both the peripheral nervous system and the central nervous system, while immunological and vascular mechanism have been related to its genesis. The disease is subclinical in a good number of patients and should be looked for directly. In others however, it is the first symptom.

Proteína Tax ( HTLV-I ), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP / Viral Tax protein expression in salivary glands of patients infected with human t-cell lymphotropic virus type I and Sicca Syndrome

Background: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. Aim: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. Material and Methods: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. Results: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. Conclusions: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.

Anticuerpos a proteínas recombinantes Ro60 Kd, Ro52 Kd y La48 Kd, en el síndrome de Sjögren primario. Utilidad de la combinación de métodos analíticos para detectar anticuerpos anti Ro y anti La / Antibodies against recombinant Ro 60 Kd, Ro 52 and La 48 Kd proteins in primary Sjogren's Syndrome. Utility of analytic methods combination to detect antibodies anti Ro and La

BACKGROUND: The use of new recombinant antigens may increase the sensitivity and specificity of the detection of anti Ro and anti La antibodies in Sjögren's syndrome. AIM: To determine the immune reactivity of sera from patients with Sjögren's syndrome, against fusion recombinant proteins (prf) Ro60 Kd, Ro52 Kd and La48 Kd expressed in E coli and recombinant protein Ro52 Kd, expressed in baculovirus (prb). MATERIAL AND METHODS: Serum samples from 46 patients with a diagnosis of Sjögren's syndrome, according to the European criteria of 1997, were studied. Using conventional ELISA assays, 32 patients had positive anti Ro antibodies (group A) and 16 patients had negative anti Ro and anti La antibodies, but had positive antinuclear antibodies or rheumatoid factors (group B). Antibodies against recombinant proteins were measured by ELISA or Western Blot. RESULTS: Reactivity against prf Ro60 was present in 69 per cent of samples from group A patients and in 36 per cent of samples from group B. Reactivity against prf Ro52 was present in 94 per cent of samples from group A and 50 per cent of samples from group B. Reactivity against prb Ro52 was present in 75 per cent of samples from group A and 40 per cent of samples from group B. Reactivity against prf La was present in 78 per cent of samples by ELISA and 97 per cent of samples by Western Blot. In 10 of 14 serum samples from group B patients, there was reactivity against at least one recombinant protein. CONCLUSIONS: A high prevalence of reactivity against recombinant Ro and La proteins was detected in serum samples from patients with Sjögren syndrome.

Clinical constellation of annular erythema associated with anti-Ro/La autoantibodies

Annular erythema (AE) associated with anti-Ro (SSA) and/or La (SSB) autoantibody in patients with Sjogren syndrome (SS) or with SS/systemic lupus erythematosus overlap syndrome (SS/SLE), has recently been described in Orientals, and it may be a counterpart of annular skin lesion of the subacute cutaneous LE seen mostly in Caucasians. The author examined five Korean AE patients in respect to dinical diversity. In this small-sample study, subtle differences appeared between individual cases regarding the serologic features and the diagnoses of the disease. Among the five cases, four had circulating anti-Ro and anti-La antibodies, and one had only anti-La. Regarding the diagnosis, one was SS/SLE, two were primary SS, and the remaining two were only "AE associated with anti-Ro/La antibody". There seem to be a wide clinical spectrum in the disease expression of AE associated with anti-Ro/La autoantibody than previously thought.

Apoptosis: enfermedades autoinmunes y otras / Apoptosis: autoimmune diseases and other

La apoptosis es un proceso fundamental en biología celular, parece constituir uno de los mecanismos claves en la regulación del crecimiento y homeostasis de órganos y tejidos. En este trabajo realizamos una breve revisón de la apoptosis, así como también de la relevancia de ella en enfermedades autoinmunes y otras, como el sida y el cáncer

Síndrome de sjögren primario: caracteristicas clínicas e inmunogenéticas

Objetivo: Examinar las características clínicas del síndrome de Sjögren (SS) primario en pacientes colombianos, y analizar la asociación de los genes HLA-DRB1 y DQB1 con la presencia y severidad de la enfermedad. Métodos: Este es un estudio transversal y comparativo. Todos los pacientes cumplieron con los criterios europeos para la clasificación de SS primario, incluyendo una biopsia positiva de las glándulas salivales menores (GSM); y fueron evaluados utilizando un registro que incluyó el compromiso exocrino y no exocrino de la enfermedad. Los anticuerpos antinucleares se determinaron por IFI en células Hep-2, los anticuerpos anti-Ro (IgG) y anti-La (IgG) se determinaron por ELISA. El polimorfismo de los genes HLA-DRB1 y DQB1 fue examinado mediante reacción en cadena de la polimerasa con iniciadores de secuencia específica. La severidad de la enfermedad fue determinada por la relación entre el puntaje por focos inflamatorios en GSM (método de Daniels) y la duración de la enfermedad (en años). Resultados: Se estudiaron 74 pacientes (97 por ciento mujeres) de Medellín y Santafé de Bogotá, y 76 individuos sanos apareados por edad, sexo y geografía. La enfermedad tuvo una presentación clínica similar a la del resto del mundo, y se asoció con el haplotipo HLA-DRB1*0301-DQB1*0201 (OR: 4.3, IC 95 por ciento: 1.6-12, p=0.002). Este a su vez se asoció con una severidad > 1 (OR: 15.5, IC 95 por ciento: 1.8-129, p=0.001), a la presencia de anticuerpos anti-Ro (OR:4.3, IC 95 por ciento:1.3-14, p=0.01). La frecuencia alélica del HLA-DQB1*0602 fue mayor en los controles (0.303) que en los pacientes (0.121) (OR:0.3, IC 95 por ciento: 0.2-0.8, p=0.01). Conclusión: El presente estudio describe las caracteráisticas clínicas del SS primario, confirmando la similitud de éstas en diferntes razas, y muestra, por primera vez en la población colombiana, la asociación del HLA-DRB1*0301-DQB1*0201 a la enfermedad y a su gravedad, así como el papel protector del HLA-DQB1*0602. La presencia de una carga negativa en la posición B71 del HLA-DRB1*0301 y DQB1*0201 así como una carga negativa en la posición b74 del hla-DQB1*0602 permite una explicación funcional del papel de estos alelos en la predisposición y protección de la enfermedad.