Clinical and applied immunology reviews最新文献

It is thought that the primary function of secretory IgA (SIgA) is, in conjunction with the mucus lining of the gut, to prevent translocation of bacteria across the epithelial barrier. In this review, we evaluate the emerging idea that SIgA and the mucus of the large bowel may actually be involved in promicrobial activity. Central to this new model is the idea that growth of bacterial biofilms in the gut may be common and is likely advantageous to the microbial community. Evidence is examined that suggests the immune system is likely involved in the maintenance of biofilms in the gut. This model of immune inclusion, if correct, likely operates in conjunction with immune exclusion, preventing bacteria from transversing the epithelial barrier.

The clinical utility of measuring antinucleosome autoantibodies (also known as antichromatin) in patients with systemic lupus erythematosus (SLE) has recently been evaluated by a number of different groups. Many studies found that antinucleosome autoantibodies were more prevalent than anti-DNA in SLE patients. In addition, antinucleosome autoantibodies were usually found to correlate with glomerulonephritis or disease activity better than anti-DNA in these patients. Antinucleosome autoantibodies are also found in patients with drug-induced lupus and Type I autoimmune hepatitis, but not usually in other diseases, thus showing good specificity for the above diseases. Several studies have shown that individuals with SLE have T cells reactive with nucleosomes and have increased levels of nucleosomes in their sera. The antinucleosome response in murine models of SLE is also T-cell–dependent and appears to be driven by self antigen. Nucleosome–antinucleosome immune complexes bind to glomeruli in vitro, and antinucleosome autoantibodies have been eluted from the kidneys of people and mice with glomerulonephritis. In one strain of mouse it was shown that antinucleosome autoantibodies were necessary, but not sufficient, to cause glomerulonephritis. These findings all show that antinucleosome autoantibodies are a sensitive and specific diagnostic marker for SLE and contribute to the pathology of glomerulonephritis.

Markers of cartilage degradation hold a great, but so far underutilized potential in the research and clinical management of joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With the rapid pace of development of such markers, they are likely to emerge as promising clinical tools for several uses. These roles may include: improving preclinical and clinical development in arthritis research; differentiation of patients with high and low turnover states at disease diagnosis; selection of optimal therapy and therapy dose for the individual patient; monitoring disease progression; and predicting disease outcome.

This review focuses on the cartilage matrix components and the metabolites from this very special tissue that have been proposed as biochemical markers. Special attention is focused on the challenges facing the development of such markers to the standards required for widespread practical use. Examples are provided on the current use of cartilage derived biochemical markers and perspectives for the future use of markers and required clinical documentation are presented.

Despite significant improvements in organ transplantation, immunosuppression is associated with rejection or drug toxicity in a significant fraction of transplant recipients. Mechanistic immunological markers may enhance the precision with which immunosuppression, post-transplant alloreactivity and graft adaptation are monitored, and thereby enhance the success of post-transplant immunosuppression. The utility of lymphocyte subset distribution and function as monitoring tools in our laboratory is predicated on observations that: stimulated responses of peripheral blood effector and antigen-presenting lymphocytes (sLR) are inhibited by immunosupressants in a concentration-dependent manner; extended phenotypic monitoring suggests that the memory T-helper population may demonstrate increasing expression of activation marker CD25 (IL-2R) upon contact with transplanted antigen; and donor-specific suppression of costimulatory molecule expression may be mediated by recipient CD8+28− lymphocytes, and is more likely to occur in those with graft adaptation than those who may be prone to rejection. Validation of these observations, and other mechanistic markers may identify newer approaches to monitor the immune system, and reduce efficacy failure with immunosuppression after solid organ transplantation.

Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disease affecting the joints. With more sophisticated and effective therapies becoming available and with the understanding that early intervention is crucial in preventing irreversible joint damage, it is more and more important to diagnose RA at a very early stage in the disease. To facilitate diagnosis during the early stages of the disease, when often not all clinical symptoms are manifest, a good serological marker is needed. Antibodies directed to citrullinated proteins provide this ability. The most sensitive assay to detect these antibodies is the so-called anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA) assay. In this review, the diagnostic and prognostic potential and the general utility in clinical practice of anti-CCP antibodies are discussed. Furthermore, we elaborate on the mechanisms involved in the generation of citrullinated autoantigens and the possible role of the anti-CCP antibodies and their antigens in the disease.

Acute rheumatic fever (ARF) is an inflammatory disease of childhood that occurs following untreated Group A streptococcal pharyngeal infections. Although it is well established that group A streptococcus is the sole etiologic agent of ARF, the pathogenesis and immune mechanisms are still not completely understood. We review the clinical manifestations, diagnostic, and therapeutic aspects of ARF. We also review recent advances in the understanding of disease pathogenesis, host susceptibility, and vaccine strategies to prevent group A streptococcal infection.

The genus Salmonella is a group of highly adaptive Gram-negative bacilli containing a number of closely related serotypes, many of which are potentially pathogenic for humans and/or animals. Salmonella infections are capable of producing serious infections that are often foodborne and present as gastroenteritis, however, a small percentage of these infections may become invasive and result in bacteremia and serious extraintestinal disease. The epidemiological characteristics of a Salmonella outbreak drive interest in the identification of the serotype and other identifiable characteristics including antimicrobial susceptibility and emergence of multidrug resistance patterns. A variety of methods have been developed to identify serotypes. Public health concerns and the potential for foodborne zoonotic transmission have made Salmonella the subject of numerous international, national, and local surveillance programs.

Influenza is unique among viral infections because of its propensity for seasonal epidemics and occasional pandemics, and because of the morbidity and mortality that result from its pulmonary complications. In contrast to the majority of viruses, effective well-tolerated influenza vaccines, antivirals and chemoprophylaxis are available. The need for a timely diagnosis, which allows for optimal use of these treatments, led to the introduction of numerous rapid diagnostic tests (with turnaround times of less than 30 minutes). However, during influenza season, clinical diagnosis (based on cough and high fever of acute onset) can be highly predictive of influenza. Thus diagnostic tests are not required for all patients with suspected influenza but may be of value if the clinical diagnosis is unclear and if antiviral or antibiotic treatment is a consideration. When evaluating performance of various rapid diagnostic tests for influenza, it is important to consider the type and quality of specimen and type of patient to be tested. Specimen-type drives performance of the rapid diagnostic tests. Swab specimens, particularly throat swabs are the most frequently submitted but least desirable specimen-type. Thus, although current rapid diagnostic tests are specific for influenza, sensitivity is highly variable. To improve diagnostic accuracy, a nasal/nasopharyngeal aspirate or sputum specimen should be obtained. Because of their highly variable sensitivity and negative predictive value, it is our opinion, that rapid diagnostic tests should only be used in influenza season and that results should be confirmed with virus culture. Despite these reservations, during influenza-season, detection of influenza by rapid diagnostic test may, potentially, be of great benefit to the patient and public health.