Mario García-Carrasco

Etiopathogenesis of Behcet's disease.

Bechets disease (BD) is an inflammatory, multi systemic disease with spontaneous remissions and relapses similar to various autoimmune diseases. BD leads to organ damage, including the eyes, skin, joints, etc., which produces various clinical manifestations. The central histopathologic characteristic is systemic vasculitis with perivascular inflammatory infiltrates. The etiopathogenesis is unknown, although immunological abnormalities, possibly induced by susceptible microbiological pathogens, have been postulated.

Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly

The immune system undergoes continuousmorphologic and functionalchanges throughoutthe years, and it is now believed that the immune response has its peak function in puberty and gradually decreases with age (immunosenescence). Recent studies in healthy octogenarian patients suggest that the immune system, instead of suffering a generalized deterioration, undergoes a remodelling/readjustment of its major functions. Increase in two contrasting phenomena coexist in immunosenescence: on the one hand, a decrease in the capacity of the immune response and, on the other hand autoantibodyproduction.The possibleconsequencesof this progressive‘ageing’ of the immune system are the increasein autoimmune phenomena, incidenceof neoplasiaand predisposition to infections. The study of autoimmune manifestations in elderly populations should be considered a priority for future medical research because of increasing life expectancy, especially in developed countries. This review analyses the main immune disorders associated with immunosenescence, the prevalence and clinical significance of autoantibodiesin the elderly and the clinical expression of the main autoimmune diseases in older patients.

Anti-chromatin antibodies in systemic lupus erythematosus: a useful marker for lupus nephropathy

Background: Anti-chromatin antibodies have recently been described in patients with systemic lupus erythematosus (SLE) and it has been suggested that their presence is associated with lupus nephritis. Objective: To assess the prevalence and clinical associations of these antibodies in SLE. Methods: The presence of anti-chromatin antibodies in 100 patients with SLE was investigated by an enzyme linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 100 patients with primary Sjögren’s syndrome, 30 with primary antiphospholipid syndrome (APS), 10 with systemic sclerosis, and 100 normal controls were also tested. Results: Positive levels were detected in 69/100 (69%) patients with SLE. In contrast, they were found in only 8/100 (8%) of those with primary Sjögren’s syndrome, in 1/10 (10%) with systemic sclerosis, in 2/30 (7%) with primary APS, and in none of the 100 healthy controls. Patients with anti-chromatin antibodies had a twofold higher prevalence of lupus nephropathy than those without these antibodies (58% v 29%, p<0.01). A significant correlation was found between the levels of anti-chromatin antibodies and disease activity score as measured by the European Consensus Lupus Activity Measurement (ECLAM; p=0.011). Conclusions: The measurement of anti-chromatin antibodies appears to be a useful addition to the laboratory tests that can help in the diagnosis and treatment of SLE. These antibodies are both sensitive and specific for SLE, and are a useful marker for an increased risk of lupus nephritis.

Immunopathogenesis of vitiligo

Vitiligo is a common depigmenting disorder which may have devastating psychological and social consequences and is characterized by the presence of circumscribed white macules in the skin due to the destruction of melanocytes in the epidermis. Various hypotheses have been proposed to explain the pathomechanisms involved in this disease, and studies have shown the participation of autoimmune processes in the pathogenesis of vitiligo. Cellular and humoral immunities have been implicated in the development of vitiligo and their role continues to be investigated. Peripheral blood and skin biopsies of patients with vitiligo show that T-cells, mononuclear cells, various pro-inflammatory cytokines, and auto-antibodies can damage melanocytes. Further research is required to determine whether autoimmunity is the main mechanism of vitiligo or only a consequence.

Thyroid disease in Sjögren’s syndrome

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 10.5xa0years. 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.

Anti-CD20 therapy in patients with refractory systemic lupus erythematosus: a longitudinal analysis of 52 Hispanic patients

The objective of this study was to investigate the efficacy and safety of anti-CD20 treatment in Hispanic patients with refractory systemic lupus erythematosus and to determine whether baseline parameters predict disease flare. Fifty-two patients with systemic lupus erythematosus, 13 with active lupus nephritis, eight with thrombocytopenia, three with leukocytopenia, 25 with severe musculoskeletal involvement and three with skin involvement) refractory to conventional therapy were treated with anti-CD20 treatment (rituximab; MabThera®, Roche) plus ongoing immunosuppressive treatment. Disease activity was assessed monthly using the SLEDAI validated for the Mexican population with a follow-up period of 6 months. At 6 months of follow-up, significant clinical improvements were detected, with a reduction in the global SLEDAI validated for the Mexican population score. Five of the 13 patients with lupus nephritis (38.4%) had a complete renal response and five (38.4%) had a partial response. Rituximab was also effective in patients with autoimmune thrombocytopenia, inducing a significant increase in platelet counts (p = 0.012). Nineteen of 25 patients with severe musculoskeletal involvement had remission of arthritis. Only one of the three patients with skin involvement had no lesions at 6 months. Rituximab treatment also allowed a reduction of the oral prednisone dose in the majority of patients. No baseline predictors of flare were found. Treatment was discontinued after the first infusion in two patients due to serum sickness and in another due to pulmonary infection. In conclusion, the addition of rituximab to conventional immunosuppressive therapy may be an effective strategy for lupus nephritis, autoimmune thrombocytopenia and inflammatory polyarthritis in patients with refractory systemic lupus erythematosus. Lupus (2010) 19, 213—219.

Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients

Backgroundu2002 Lupus erythematosus (LE) is a chronic, autoimmune disease resulting from an interaction of genetic, environmental and hormonal factors and characterized by a spectrum of clinical forms with variable evolution from a localized cutaneous form to a life‐threatening systemic form.

Use of rituximab in patients with systemic lupus erythematosus: An update

Systemic lupus erythematosus (SLE) is a chronic, occasionally life threatening, multisystem disorder. Patients suffer from a wide group of symptoms and have a variable prognosis that depends of the severity and type of organ involvement. The clinical manifestations include fever, skin lesions, arthritis, neurologic, renal, cardiac, and pulmonary disease. The pathogenesis of this serious multisystem autoimmune disease is based on polyclonal B cell immunity, which involves connective tissue and blood vessels. The novel biologic therapies have raised hope for more effective and safer treatment for SLE. Although definitive studies are still under development, the impressive preliminary results of therapies specifically targeting B cells and the signaling pathways involved in B-T-cell interactions suggest that the depletion of memory cells accounts, at least in part, for the clinical efficacy of rituximab therapy in patients whose disease is resistant to other immunosuppressive therapies. However these findings, although provocative, require further investigation in larger cohorts.

Risk factors of vertebral fractures in women with systemic lupus erythematosus.

The aim of the current study was to analyze the role of traditional and systemic lupus erythematosus (SLE)-related risk factors in the development of vertebral fractures. A cross-sectional study was performed in women with SLE attending a single center. A vertebral fracture was defined as a reduction of at least 20% of vertebral body height. Two hundred ten patients were studied, with median age of 43xa0years and median disease duration of 72xa0months. Osteopenia was present in 50.3% of patients and osteoporosis in 17.4%. At least one vertebral fracture was detected in 26.1%. Patients with vertebral fractures had a higher mean age (50u2009±u200914 vs. 41u2009±u200913.2xa0years, pu2009=u20090.001), disease damage (57.1% vs. 34.4%, pu2009=u20090.001), lower bone mineral density (BMD) at the total hip (0.902u2009±u20090.160 vs. 982u2009±u20090.137xa0g/cm2, pu2009=u20090.002), and postmenopausal status (61.9% vs. 45.3%, pu2009=u20090.048). Stepwise logistic regression analysis revealed that only age (pu2009=u20090.001) and low BMD at the total hip (pu2009=u20090.007) remained as significant factors for the presence of vertebral fracture. The high prevalence of vertebral fractures in the relatively young population implies that more attention must be paid to detect and treat vertebral fractures.

Primary Sjögren's syndrome in the elderly: clinical and immunological characteristics.

The objective of the study was to determine the clinical and immunological characteristics of primary Sjoögrens syndrome (SS) in patients with an older onset of the disease. We included 223 consecutive patients (204 female and 19 male; mean age at onset 53 years; range 15-87 years) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 31 patients the onset of disease occurred after the age of 70 years, and they represent the elderly-onset group described in this report. The remaining 192 patients presented disease onset before the age of 70 years, and they represent the younger-onset group. Of the 31 (14%) patients with elderly onset of primary SS, 26 were female and 5 male, and the disease onset occurred between 70 and 87 years (mean 74 years). The most common extraglandular manifestations were articular involvement (29%), hepatic involvement (20%), peripheral neuropathy (16%) and interstitial pneumopathy (13%). When compared with patients with a younger onset, the prevalences of glandular and extraglandular manifestations and immunological features (cryoglobulinemia, hypocomplementemia and positivity for RF, anti-Ro/SS-A or anti-La/SS-B) were similar in both groups. In conclusion, although primary SS is typically a disease of middle-aged adults, clinicians should note that it may be diagnosed frequently among elderly patients. However, we could not found any notable differences in clinical and immunological characteristics of patients with elderly onset of primary SS.