Israel Medical Association Journal

High mobility group box 1 is a nuclear protein participating in chromatin architecture and transcriptional regulation. When released from cells, HMGB1[1] can also act as a pro-inflammatory mediator or alarmin. Upon stimulation with lipopolysaccharides or tumor necrosis factor-alpha, HMGB1 is secreted from certain cells such as monocytes/macrophages and fosters inflammatory responses. In addition, HMGB1 is passively released from necrotic cells and mediates inflammation and immune activation. In contrast, during apoptotic cell death, nuclear HMGB1 gets tightly attached to hypo-acetylated chromatin and is not released into the extracellular milieu, thereby preventing an inflammatory response. There is accumulating evidence that extracellular HMGB1 contributes to the pathogenesis of many inflammatory diseases, including autoimmune diseases. Increased concentrations of HMGB1 have been detected in the synovial fluid of patients with rheumatoid arthritis. In animal models of RA[2], HMGB1 appears to be crucially involved in the pathogenesis of arthritis, since neutralization of HMGB1 significantly ameliorates the disease. Also, in the serum and plasma of patients with systemic lupus erythematosus we detected substantial amounts of HMGB1, which may contribute to the disease process. However, investigations of blood concentrations of HMGB1 and its relevance in human diseases are hindered by the lack of reliable routine test systems.

Medical screening is not a tangible existent tool in autoimmune disorders as it is in other illnesses. Numerous attempts are made to identify individuals destined to develop an autoimmune disease, including analysis of the genetic background, which along with the immunological profile, may assist in identifying those individuals. If these efforts turn out to be successful they may lead to the possibility of proactive measures that might prevent the emergence of such disorders. This review will summarize the attempts made to pursue autoantibodies specific for the central nervous system as potential predictors of autoimmune neurological disorders.

Among the several mechanisms that play a role in maintaining peripheral self-tolerance is the existence of a unique CD4+CD25+ population of naturally occurring regulatory T cells, which actively prevent both the activation and the effector function of autoreactive T cells that have escaped different mechanisms of tolerance. Many studies have shown the benefit of targeting this cell population by restoring self-tolerance. Therapies that could possibly increase the suppressive ability of T regulatory cells were proven to improve the course of autoimmune diseases.

Background: Chronic obstructive pulmonary disease is an increasing cause of chronic morbidity and mortality around the world. The major cause of the disease is smoking. Despite the gravity of the problem there is no knowledge of its rate in the Israeli smoking population.

Objectives: To assess the prevalence of COPD[1]and early lung cancer among smokers.

Methods: People aged 45 up to 75 with a history of at least 20 pack-years cigarette smoking, including quitters, were screened for COPD. They were interviewed and a spirometry was performed.

Results: Of the 1150 people recruited 92% underwent and performed acceptable spirometry; 22% of these subjects had airflow limitation and were diagnosed with COPD according to the GOLD classification. Only 4% had been diagnosed as COPD prior to this screening. The majority of those tested were unaware of or unconcerned about developing the disease. There was no correlation between pack-years smoking and development of COPD, but there was a relative correlation of pack-years smoking and severity of COPD, particularly in the older group only (r = 0.42).

Conclusions: About one-fifth of the smokers aged 45 and up developed COPD. There is a significant gap between the disease distribution and its awareness in the population at risk. The need for a national screening program and early diagnosis of COPD in people at risk is needed.