Rheumatoid Arthritis: Latin America

Soriano ER, Galarza-Maldonado C, Cardiel MH, Pons-Estel BA, Massardo L, Caballero-Uribe CV, Achurra-Castillo AF, Barile-Fabris LA, Chávez-Corrales J, Díaz-Coto JF, Esteva-Spinetti MH, Guibert-Toledano M, Palazuelos FI, Keiserman MW, Lomonte AV, Mota LM, Pineda Villaseñor C, Alarcón GS, Anonymous00427. · Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires y Fundación Dr Pedro M. Catoggio para el Progreso de la Reumatología, Buenos Aires, Argentina. · Rheumatology (Oxford). · Pubmed #18463144 links to  free full text

This publication has no abstract.

Tristano AG. · Department of Internal Medicine, Dr. Domingo Luciani Hospital, Caracas, Venezuela. · Med Sci Monit. · Pubmed #18301366 links to  free full text

Abstract: Macrophage activation syndrome (MAS) or hemophagocytic syndrome is a severe complication of chronic rheumatic diseases especially in systemic-onset juvenile rheumatoid arthritis (JRA). Although the cause of MAS is unknown, dysregulation of macrophage-lymphocyte interactions with subsequent increases in the levels of both T cell-derived and macrophage-derived cytokines could be involved in this syndrome, leading to an intense systemic inflammatory reaction, which accounts for the main clinical picture. Patients usually present with an acute febrile illness, hepatosplenomegaly, lymphadenopathy, cutaneous and mucosal bleeding, pancytopenia, and central nervous system, cardiac, and renal involvement. Treatment of MAS in patients with rheumatic diseases has not been standardized yet, but it commonly includes a variety of agents such as high-dose corticosteroids, cyclosporine, cyclophosphamide, etoposide, and intravenous immunoglobulin (IVIG). This article reviews the current literature about the pathogenesis, clinical manifestation, diagnosis, and treatment of this severe complication associated with rheumatic diseases.

Burgos RA, Hidalgo MA, Figueroa CD, Conejeros I, Hancke JL. · Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Casilla 567, Valdivia, Chile. · Mini Rev Med Chem. · Pubmed #19200021 No free full text.

Abstract: The importance of neutrophils in human disease such as rheumatoid arthritis, asthma, adult respiratory distress syndrome, and COPD has prompted the search for drugs capable to slow down neutrophil-dependent inflammation, without interference with innate immune responses. In this review, we summarize new potential drugs targets against neutrophils mediated inflammatory responses.

Contreras-Ruiz J, Kresch-Tronik NS, de la Cruz-Garcia MI, Mercado-Ceja S, Lozano-Platonoff A. · Interdisciplinary Wound and Ostomy Care Center, Dr. Manuel Gea Gonzalez General Hospital, Mexico City, Mexico. · Ostomy Wound Manage. · Pubmed #19037135 No free full text.

Abstract: Pyoderma gangrenosum (PD) is a rare, chronic, relapsing, ulcerative, neutrophilic cutaneous disease and may be difficult to recognize. It is not uncommon for PD to be mistakenly diagnosed as vascular occlusive or venous disease, vasculitis, cancer, infection, exogenous tissue injury, or other inflammatory disorders. A 55-year-old woman with a 5-year history of a very painful and enlarging ulcer presented at the authors' clinic. Previously, based on an original diagnosis of venous ulcer, the wound had been surgically debrided and managed with saline-soaked gauze and compression therapy. After the authors secured a complete history (which included rheumatoid arthritis) and assessment, PD was suspected. A biopsy was performed for histological confirmation. Pyoderma gangrenosum treatment, including oral corticosteroids and topical 0.01% tacrolimus twice daily covered with nonadhesive gauze and compression wrapping, was started. After 4 weeks, the wound had improved noticeably and pain medications to manage wound pain were discontinued. The wound was completely healed after 4 months. The presence or absence of PD must be ascertained in all patients who present with a history of painful lower leg ulcers and PD risk factors, such as rheumatoid arthritis.

Tristano AG. · University Hospital of Caracas, Venezuela. · Int Immunopharmacol. · Pubmed #18848912 No free full text.

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation and proliferation of inflammatory cells in the synovial (joint) lining, resulting in the formation of pannus tissue, which invades and destroys adjacent cartilage and bone. In RA macrophages, B cells, mast cells, fibroblast-like synoviocytes (FLSs) and CD4+ T lymphocytes become activated and contribute to synovial inflammation and joint destruction. It has been showed that different tyrosine kinases participate in the activation of those cells having important participation in the physiopathology of RA. Therefore, the tyrosine kinases inhibitors could be the next step in the treatment of patients with RA. This review focuses on recent advances on the role of tyrosine kinases and their inhibitors in the physiopathology of RA.

Zuardi AW. · Department of Neurology, Psychiatry and Medical Psychology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. · Rev Bras Psiquiatr. · Pubmed #18833429 links to  free full text

Abstract: OBJECTIVE: The aim of this review is to describe the historical development of research on cannabidiol. METHOD: This review was carried out on reports drawn from Medline, Web of Science and SciELO. DISCUSSION: After the elucidation of the chemical structure of cannabidiol in 1963, the initial studies showed that cannabidiol was unable to mimic the effects of Cannabis. In the 1970's the number of publications on cannabidiol reached a first peak, having the research focused mainly on the interaction with delta9-THC and its antiepileptic and sedative effects. The following two decades showed lower degree of interest, and the potential therapeutic properties of cannabidiol investigated were mainly the anxiolytic, antipsychotic and on motor diseases effects. The last five years have shown a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. These studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson's disease, Alzheimer's disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer. CONCLUSION: In the last 45 years it has been possible to demonstrate that CBD has a wide range of pharmacological effects, many of which being of great therapeutic interest, but still waiting to be confirmed by clinical trials.

Pereira IA, Borba EF. · Rheumatology Division, Federal University of Santa Catarina, Brazil. · Swiss Med Wkly. · Pubmed #18803034 links to  free full text

Abstract: The pathogenesis of atherosclerosis has not been well defined and many questions remain unanswered. Many studies have discussed the importance of inflammation as the first step in promoting endothelial dysfunction and atherosclerosis.The association of inflammatory markers such as fibrinogen and C reactive protein (CRP) with atherosclerosis and cardiovascular/cerebrovascular clinical events reinforces the pivotal role that inflammation plays in the atherosclerotic process.The humoral and cellular autoimmune response against antigens expressed in the endothelium and the greater prevalence of atherosclerosis in immune-mediated rheumatic diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) strongly suggest the involvement of autoimmunity in the atherosclerotic process. The role of inflammation and autoimmune responses in atherosclerosis are discussed in order to better understand their close link on its pathogenesis.

Filippin LI, Vercelino R, Marroni NP, Xavier RM. · Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. · Clin Exp Immunol. · Pubmed #18422737 links to  free full text

Abstract: Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa-B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis.

Pereira IA, Borba EF. · Division of Rheumatology, Federal University of Santa Catarina, Florianópolis, Brazil. · Acta Reumatol Port. · Pubmed #18344921 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease that presents not only involvement of joints but also endothelial dysfunction, dyslipidemia, and premature atherosclerosis. The death rate in RA is known to be higher than in the general population and clinical cardiovascular events secondary to atherosclerosis are responsible for the excessive death rate. A better understanding of the mechanisms that take part in the pathogenesis of atherosclerosis in RA patients is needed. Thus, the authors review the role of several factors involved in RA atherosclerosis, including disease activity, new cardiovascular risk factors, dyslipidemia and the association of atherosclerosis with the use of anti-rheumatic drugs, glucocorticoids and anti-tumor necrosis factor (TNF) agents. The role of humoral autoimmunity, namely autoantibodies against heat shock proteins, cardiolipin and beta2-glycoprotein I, and its link with atherosclerosis is also discussed. It is likely that the elucidation of the key mechanisms of atherogenesis in RA may determine a positive impact by reducing cardiovascular morbidity and mortality of these patients.

Petronilho F, Roesler R, Schwartsmann G, Dal Pizzol F. · Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. · Inflamm Allergy Drug Targets. · Pubmed #18220954 No free full text.

Abstract: Bombesin-like peptides (BLP) and its receptors are widely distributed in mammalian peripheral tissues and in the central nervous system. Recently, effects of these peptides on the production and release of cytokines were described both in animal models and humans with inflammatory diseases. Some pathological conditions such as exposure to tobacco smoke, chronic obstructive pulmonary diseases and eosinophilic granuloma have recently been found to be associated with an increase of pulmonary BLP-producing cells. Proinflammatory neuropeptides have a key role in the pathogenesis and maintenance of rheumatoid arthritis and sepsis. Together, these findings support the view that the GRPR should be considered a therapeutic target for a subset of inflammatory diseases.

Santiago MB, Galvão V. · Rheumatology Service, Hospital Santa Izabel, Praça Almeida Couto 500, Nazaré, Salvador, Bahia, Brazil. · Medicine (Baltimore). · Pubmed #18204369 No free full text.

Abstract: Jaccoud arthropathy (JA) was initially described in patients with rheumatic fever and later in several other rheumatologic conditions, particularly systemic lupus erythematosus (SLE). In patients with the latter disorder, a prevalence of about 5% has been observed. We conducted the current study to describe a series of patients with SLE with JA, followed at the Hospital Santa Izabel, Salvador, Brazil, during the year 2006. We reviewed the literature on JA, with emphasis on the histologic, clinical, radiologic, and therapeutic aspects of the condition. Twenty-one patients with JA were identified, corresponding to a prevalence of 3.47% in the population of 606 patients with the diagnosis of SLE attended in our service. Twenty patients were women, and the mean age was 40.2 +/- 8.8 years (range, 24-55 yr). The most frequently found joint deformities were swan neck and thumb subluxation, both identified in 14 patients. Ulnar deviation was seen in 8, boutonniere deformity in 3, and hallux valgus in 2 patients. We found no difference in the clinical or laboratory features in SLE patients with or without JA. The patients with JA presented a trend toward a lower quality of life compared with the patients with SLE without JA, but without statistical significance.

Rosa SB, Voltarelli JC, Chies JA, Pranke P. · Laboratório de Hematologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil. · Braz J Med Biol Res. · Pubmed #17713674 links to  free full text

Abstract: Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplantation in such diseases aims to destroy the self-reacting immune cells and produce a new functional immune system, as well as substitute cells for tissue damaged in the course of the disease. Significant results, such as the reestablishment of tolerance and a decrease in the recurrence of autoimmune disease, have been reported following stem cell transplantation in patients with autoimmune disease in Brazil and throughout the world. These results suggest that stem cell transplantation has the potential to become an important therapeutic approach to the treatment of various autoimmune diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, Crohn's disease, autoimmune blood cytopenias, and type I diabetes mellitus.

Grinblat B, Scheinberg M. · Physician, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. · Semin Arthritis Rheum. · Pubmed #17640718 No free full text.

Abstract: OBJECTIVES: The paradoxical observation that antitumor necrosis factor (anti-TNF) agents are capable of inducing psoriasis and psoriasiform skin lesions while also being therapy for psoriasis gained substantial support following the description of this condition by several authors. Our aim was to review the literature of this subject. METHODS: A retrospective review of the literature was performed using the Medline database between 2005 and February 2007. RESULTS: Since the first publication by our group in April 2005 to the present, 50 cases of this type of dermatitis have been described. More than half of the cases were associated with the use of infliximab. Different presentations of psoriasis were reported, plaque form being the most prevalent. A number of clinical and immunological observations suggest a cytokine disequilibrium in patients receiving chronic anti-TNF therapy leading to this condition. Treatment for the skin disease includes changing the anti-TNF agent or discontinuing the medication. CONCLUSIONS: The appearance of psoriasis and psoriasiform lesions during chronic anti-TNF therapy is dependent on the presence of known and unknown interrelated factors. Enhanced clinician awareness of this drug complication and further investigation of its mechanisms are warranted.

Bortoli R, Santiago M. · Serviço de Reumatologia do Hospital Santa Izabel, Praça Conselheiro Almeida Couto, 500, Nazaré, Salvador, CEP, 40000-000, Bahia, Brazil. · Clin Rheumatol. · Pubmed #17594118 No free full text.

Abstract: Chloroquine (CQ), a 4-aminoquinoline drug, has been largely used for the treatment of rheumatoid arthritis and other connective tissue diseases. Besides the well-known retinal toxicity, its use has been suspected of be associated to ototoxicity. Some reports have described mainly sensorineural hearing loss, tinnitus, sense of imbalance, and cochleovestibular manifestations. Differently from what occurs in retinopathy, in which there is a predominance of CQ toxicity, there are reports of alterations in hearing related to either CQ or hydroxychloroquine. Brain-evoked response audiometry seems to be the most sensitive test in detecting early manifestations of cochlear injury caused by CQ when still in a reversible stage. The reversibility of CQ ototoxicity has been debatable, but there is suggestion that such complication can be corrected if the medication is stopped and appropriate therapy, with steroids and plasma expanders, is instituted.

Jara LJ, Navarro C, Brito-Zerón Mdel P, García-Carrasco M, Escárcega RO, Ramos-Casals M. · Direction of Education and Research, Hospital de Especialidades, Centro Médico La Raza, IMSS, Seris y Zaachila s/n C.P., 02990, Mexico City, México. · Clin Rheumatol. · Pubmed #17558463 No free full text.

Abstract: From 1960 to 2007, an important number of patients with primary Sjögren's syndrome (pSS) along with thyroid disease diagnosed by laboratory data and clinical presentation were reported. The most common thyroid disorder found was autoimmune thyroiditis and the most common hormonal pattern was subclinical hypothyroidism. The coexistence of SS and thyroiditis is frequent and suggests a common genetic or environmental factor predisposition with similar pathogenic mechanisms. pSS was ten times more frequent in patients with autoimmune thyroid disease and autoimmune thyroiditis was nine times more frequent in pSS. Therefore, SS should be studied in patients with thyroid disease and vice versa. Antigens are shared by both thyroid and salivary glands, which could be responsible for the association between both diseases. Immunogenetic studies had suggested that both diseases have a common genetic predisposition. pSS and thyroid disease patients were mostly women with positive antithyroglobulin, antiparietal cell and antithyroid peroxidase antibodies. Thyroid dysfunction is frequent in pSS patients and those prone to develop thyroid disorders are identified by thyroid-related autoantibodies or by rheumatoid factor and anti-Ro/SSA activity. Patients with pSS have an increased tendency to develop other autoimmune diseases. Hypothyroidism was the most common autoimmune disease developed in pSS patients during follow-up of 10.5 years. Lymphomas are also associated with SS and thyroiditis and a 67-fold increased risk for thyroid mucosa-associated lymphoid tissue (MALT) lymphoma and a 44-fold increased risk for parotid lymphoma is being attributed to autoimmune thyroiditis and pSS. It is suggested that immune mechanism deficiency is a causal factor for B cell lymphoma in pSS and autoimmune thyroid disease. Other studies are necessary to clarify the shared pathogenesis mechanism in SS and autoimmune thyroid disease and to understand this fascinating autoimmune association.

Vitale RF, Ribeiro Fde A. · Otorhinus Clinic and Hospital Santa Marcelina, Brazil. · Braz J Otorhinolaryngol. · Pubmed #17505610 links to  free full text

Abstract: Cholesteatoma may cause bone erosion, with high morbidity and mortality rates. Tumor necrosis factor-alpha (TNF-a) is one of the main cytokines involved in this process. Our goal was to evaluate the role of TNF-a in Bone Resorption and its effect on cholesteatoma. MATERIAL AND METHODS: analysis and critical literature review. RESULTS: Different studies have demonstrated that TNF-a is capable of causing bone erosion. It may stimulate the differentiation and maturation of osteoclasts or it may act on the bone matrix, exposing it to the action of the osteoclasts. It is possible to inhibit TNF-a, reducing its effects and prevent bone loss in illnesses such as rheumatoid arthritis,and there has been no specific investigation regarding cholesteatomas. All studies agree on the importance of TNF-a in the bone resorption process present in cholesteatomas, and on the degree of destruction observed; however, there is no consensus as to its location. These differences are probably due to receptor site. CONCLUSION: TNF-a, present in cholesteatomas, promotes bone resorption, along with other cytokines (RANKL and IL-1) related to complications.

Thompson-Chagoyán OC, Maldonado J, Gil A. · Department of Paediatrics, "Los Venados" General Hospital, Mexican Institute of Social Security, México City, Mexico. · Dig Dis Sci. · Pubmed #17420934 No free full text.

Abstract: The aim of this study was to review the process of microbial colonization and the environmental and host factors that influence colonization and microbial succession. The impact of some diseases on intestinal microbiota composition is also described. Microbial colonization of the gut by maternal vaginal and fecal bacteria begins during and after birth. During the first 2 years of life, specific microbes become established in a process designated microbial succession. Microbial succession in the gastrointestinal tract is influenced by numerous external and internal host-related factors, and by the second year of life, the intestinal microbiota composition is considered identical to that of adults. Nevertheless, intestinal microbiota in both infants and adults remain incompletely characterized and their diversity poorly defined. The main explanation is that many intestinal bacteria that live in an anaerobic environment are difficult or impossible to culture outside the intestine. However, recent advances in molecular biology techniques have initiated the description of new bacteria species. The composition of gut microbiota can be modulated by host, environmental, and bacterial factors, and strong evidence has emerged of substantial modifications during illness or exposure to threatening experiences. It has been postulated that improvements in hygienic measures have led to an increase in allergic diseases ("hygiene hypothesis"). Alterations in gut microbiota and their functions have been widely associated with many chronic and degenerative diseases, including inflammatory bowel disease, colon cancer, and rheumatoid arthritis.

Martinez JB, Valero JS, Bautista AJ, Restrepo JF, Matteson EL, Rondon F, Iglesias-Gamarra A. · Internal Medicine and Rheumatology, National University of Colombia, Bogota, Colombia. · Clin Exp Rheumatol. · Pubmed #17417990 No free full text.

Abstract: OBJECTIVE: To describe the occurrence of erosive arthropathy in systemic lupus erythematosus (SLE) and its relationship to anti-CCP antibodies. METHODS: Retrospective medical record review of a case series of five female patients with SLE and erosive arthropathies. RESULTS: The initial disease presentation in all patients was a polyarthritis. Anti-CCP antibodies were detected in 4 out of 5 (80%) patients, 2 of whom had a positive rheumatoid factor. CONCLUSION: Erosive arthritis was strongly associated with the presence of anti-CCP antibodies in these patients with SLE, who presented with polyarthritis. Anti-CCP in patients with SLE may be a marker of a more severe joint disease.

Carvalho JF, Blank M, Shoenfeld Y. · Rheumatology Division, São Paulo University, School of Medicine, São Paulo, Brazil. · J Clin Immunol. · Pubmed #17340192 No free full text.

Abstract: Vascular endothelial growth factor (VEGF) is a potent stimulating factor for angiogenesis and vascular permeability. There are eight isoforms with different and sometimes overlapping functions. The mechanisms of action are under investigation with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins, which were not previously associated to angiogenesis. VEGF has important physiological actions on embryonic development, healing, and menstrual cycle. It also has a great role in pathological conditions that are associated to autoimmune diseases. There is considerable evidence in various autoimmune diseases such as in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis of an interrelationship between the VEGF system and theses disorders. Serum levels of VEGF correlate with disease activity in a large number of autoimmune diseases and fall with the use of standard therapy. We raised the possible future therapeutic strategies in autoimmune diseases with the anti-VEGF or anti-VEGFR (receptor). So far, this therapy has been used in cancer and macular ocular degeneration in diabetes. This review outlines the evidence for VEGF participation in various autoimmune diseases and proposes lines for future research in this field.

Lotito AP, Silva CA, Mello SB. · Department of Paediatrics, University of Sao Paulo, Brazil. · Autoimmun Rev. · Pubmed #17317618 No free full text.

Abstract: Interleukin-18 is a cytokine member of the IL-1 super family that seems to exert powerful Th1-promoting activities in synergy with IL-12. Here we describe the participation of IL-18 in inflammatory joint diseases, in particular rheumatoid arthritis, adult onset Still's disease and juvenile idiopathic arthritis. The emphasis of this study was to summarize in vivo and in vitro studies that focused the action of this pro-inflammatory cytokine on the arthritic process as well as its role in the complex network of chemical mediators involved.

Delgado-Vega AM, Martín J, Granados J, Anaya JM. · Unidad de Biología Celular e Inmunogenética, Corporación para Investigaciones Biológicas (CIB), Universidad del Rosario, Medellín, Colombia. · Biomedica. · Pubmed #17315483 No free full text.

Abstract: Rheumatoid arthritis is a chronic and systemic autoimmune disease characterized by inflammation and destruction of the synovial joints. It affects approximately 0.5% of the Latin-American population and is three times more common in women than in men. Evidence of familial aggregation (lambdas=2-17) was the first indication of a genetic susceptibility to disease. As in other autoimmune diseases, it has a complex genetic basis. Results from whole-genome scans indicate that the HLA region contains a significant and consistent set of linked loci. However, HLA accounts for only one-third of the genetic susceptibility of disease, indicating that non-HLA genes are also involved in the disease susceptibility. In Latin-America, association with HLA-DRB1*0404 and TNF -308A alleles has been uniformly established; however, many other candidate genes remain to be studied. The identification of genetic factors conferring susceptibility to rheumatoid arthritis will contribute to the knowledge of the pathogenic mechanisms, ability to predict its occurrence, the development of diagnostic tools, prognosis, and treatment. The genetic epidemiology of rheumatoid arthritis is herein reviewed; a set of recommendations is provided for the design, analysis and interpretation of genetic association studies in the context of Latin-American populations.

Anaya JM, Delgado-Vega AM, Castiblanco J. · Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biológicas, Medllín, Colombia. · Clin Dev Immunol. · Pubmed #17162364 links to  free full text

Abstract: Sjögren's syndrome (SS) is a late-onset chronic autoimmune disease (AID) affecting the exocrine glands, mainly the salivary and lachrymal. Genetic studies on twins with primary SS have not been performed, and only a few case reports describing twins have been published. The prevalence of primary SS in siblings has been estimated to be 0.09% while the reported general prevalence of the disease is approximately 0.1%. The observed aggregation of AIDs in families of patients with primary SS is nevertheless supportive for a genetic component in its etiology. In the absence of chromosomal regions identified by linkage studies, research has focused on candidate gene approaches (by biological plausibility) rather than on positional approaches. Ancestral haplotype 8.1 as well as TNF, IL10 and SSA1 loci have been consistently associated with the disease although they are not specific for SS. In this review, the genetic component of SS is discussed on the basis of three known observations: (a) age at onset and sex-dependent presentation, (b) familial clustering of the disease, and (c) dissection of the genetic component. Since there is no strong evidence for a specific genetic component in SS, a large international and collaborative study would be suitable to assess the genetics of this disorder.

Goecke A, Guerrero J. · Rheumatology Service, Internal Medicine Department, Clinical Hospital, University of Chile, Santiago, Chile. · Immunobiology. · Pubmed #16446173 No free full text.

Abstract: Glucocorticoids (GC) are hormones with a wide variety of actions, including profound anti-inflammatory/immunosuppressive effects. Their actions are mediated by an intracellular receptor called the glucocorticoid receptor (GCR). The classical GCR that mediates the hormone response is called GCR alpha. Recently however, many GCR isotypes have been described. A defective GC action has been proposed as an etio-pathogenic mechanism for the development of inflammatory/autoimmune diseases. Inadequate GC actions may have multiple causes such as: defective hypothalamic-pituitary-adrenal axis function, GC export from cells, hormone metabolization into inactive compounds and modifications of the GC receptor, among others. In 1995, a dominant negative effect of a GC receptor isotype termed beta was described; starting a still unsolved controversy about the role of GCR beta as an inducer of GC resistance in certain pathological conditions. The present article will review the data about a possible role for GCR beta in the development of GC resistance in inflammatory diseases. This review will especially focus on the role of the GCR beta in rheumatoid arthritis and in septic shock as examples of a chronic inflammatory disease and an acute systemic inflammatory condition. Original data supporting possible hyperexpression of GCR beta in both conditions will be shown.

Aguillón JC, Cruzat A, Aravena O, Salazar L, Llanos C, Cuchacovich M. · Disciplinary Program of Immunology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile. · Immunobiology. · Pubmed #16446172 No free full text.

Abstract: Tumour necrosis factor (TNF), a cytokine mainly produced by macrophages, is associated with a broad spectrum of biological effects, mainly associated with the host defense against microbes. The TNF gene is located on chromosome six within the major histocompatibility complex (MHC). Rheumatoid arthritis (RA) is a systemic autoimmune disease where TNF plays a central role in its etiology and pathogenesis. Written medical evidence of RA can be traced at least as far back as the 17th century, while human paleopathological studies appear to show the presence of RA prior to this period. The fact that RA has experienced an increment both in severity and mortality could be explained by many causes, particularly the crucial role of the immune system. Single-nucleotide polymorphisms (SNPs) are the most common genetic variations and occur at a frequency of approximately 1 in 1000 bp throughout the genome. The -308 TNF SNP is a mutation that affects the promoter region of the TNF gene. It defines the TNF1 and TNF2 alleles, determining low and high levels of TNF expression, respectively. The presence of the TNF2 allele has also been linked to increased susceptibility to and severity in a variety of autoimmune and inflammatory disorders, including RA, systemic lupus erythematosus, and ankylosing spondylitis. Studies on the functional significance of -308 SNP have detected higher levels of TNF production by cells from TNF2-carrying individuals than cells from TNF1 individuals. This difference does not appear to be due to other genes lying within the MHC region. Since the presence of the TNF2 allele may increase the host's resistance to local infection, by increasing local production of TNF at the infection site, we may suggest that such a mutation has emerged as a selective advantage to carriers of the TNF2 allele. This hypothesis may prove itself by observing the high incidence of tuberculosis and other infectious processes in those patients treated with anti-TNF therapy. Since the human lifespan has increased, the persistence of the TNF2 allele at high frequency in the population now confers what appears to be a marked survival disadvantage. As a result of the disregulation of the immune system, the genetically-predisposed host expresses larger amounts of TNF, leading to chronic inflammatory processes and autoimmune diseases, currently more prevalent. We suggest that RA, a relatively new and increasingly frequent disease, is favored by the presence of the -308 TNF promoter polymorphism, responsible for increased TNF production.

Modesto dos Santos V, Cézar BF, Barbosa ER, Carvalho FR. · Armed Forces Hospital, Brasília-DF, Brazil. · Br J Hosp Med (Lond). · Pubmed #16417121 No free full text.

This publication has no abstract.