Current Immunology Reviews (Discontinued) - Volume 8, Issue 4, 2012

Polyglandular Autoimmune Syndromes (PAS) form different clusters of autoimmune disorders characterized by the coexistence of at least two glandular autoimmune mediated diseases [1]. They are generally classified into three types: a very rare juvenile type 1(PAS I) and a relatively common adult type with (PAS II) or without adrenal failure (PAS III) [2, 3]. PAS I, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is associated with candidiasis, hypoparathyroidism, and adrenal failure. PAS II is associated with adrenal failure, thyroid diseases and type 1 diabetes mellitus. In this review we will shed light on both types of PAS including their clinical picture and ways of management.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease, rare and of unknown etiology, that affects patients who lack tolerance to self antigens. Genetic and environmental factors are related to the disease etiology. The pathology, mainly prevalent in females, is characterized by the presence of interface hepatitis with biochemical changes, such as increased levels of transaminase, the presence of hypergammaglobulinemia and circulating autoantibodies. Antibodies classify the types of the disease. Due to the heterogeneity of symptoms, the diagnostic criteria are not unique since they are based on a combination of clinical, biochemical, immunological and histological features. AIH should be diagnosed in its early stages due to possible cirrhosis evolution when untreated. Standard and most effective treatment consists of corticosteroids in combination or not with azathioprine. AIH has a good prognosis with good resolution of symptoms when properly treated, albeit with relapse at an early withdrawal.

All sensory modalities are essentially important, but pain serves a protective function and is indispensable for survival, and, technically, pain is considered one of the most common symptoms of injuries and related diseases. Inflammatory cells and inflammatory mediators are crucially involved in the propensity, genesis, persistence and severity of pain, commonly known as nociception or hyperalgesia, following trauma, infection, or nerve injury. When it pins down to the essential understanding of pain/hyperalgesia pathways and their intricate interactions with myriad probabilities of milieu of inflammatory cytokines and related molecules, the amicable concept of specificity and complexity remains a major dilemma. Various hyperalgesic models have been established to investigate this intricate relationship between pain perception and inflammatory responses. Illness-induced hyperalgesia, for instance, is one of the most common aspects of pain related-inflammation and therapeutic approach to this pain should aim at interfering with various mediators of the inflammatory reactions, including neuropeptides, eicosanoids and cytokines. In this surgical synopsis, a trajectory of neurochemical events and cascades are delineated and unraveled in terms of the connection that has ostensibly evolved for hyperalgesia-inflammatory responses. The unprecedented intricacy of pain-inflammatory relationship and putative pathways bears surmountable clinical and physiological relevance.

The innate-like natural killer T (NKT) cells are essential regulators of immunity. These cells comprise at least two distinct subsets and recognize different lipid antigens presented by the MHC class I like molecules CD1d. The CD1ddependent recognition pathway of NKT cells is highly conserved from mouse to humans. While most type I NKT cells can recognize αGalCer and express a semi-invariant T cell receptor (TCR), a major population of type II NKT cells reactive to sulfatide utilizes an oligoclonal TCR. Furthermore TCR recognition features of NKT subsets are also distinctive with almost parallel as opposed to perpendicular footprints on the CD1d molecules for the type I and type II NKT cells respectively. Here we present a view based upon the recent studies in different clinical and experimental settings that while type I NKT cells are more often pathogenic, they may also be regulatory. On the other hand, sulfatidereactive type II NKT cells mostly play an inhibitory role in the control of autoimmune and inflammatory diseases. Since the activity and cytokine secretion profiles of NKT cell subsets can be modulated differently by lipid ligands or their analogs, novel immunotherapeutic strategies are being developed for their differential activation for potential intervention in inflammatory diseases.

Atherosclerosis is a chronic inflammatory disease that contributes to majority of cardiovascular morbidity and mortality in the world. Immune system is involved in atherogenesis and disease pathogenesis. Several studies have suggested a pivotal role for immune response to autoantigens, particularly oxidized lipoproteins and heat shock proteins, in the development of the disease. Several autoimmune disorders such as inflammatory bowel disease (IBD), rheumatoid arthritis, psoriasis, diabetes type1, multiple sclerosis, chronic obstructive pulmonary disease (COPD) and systemic lupus erythematosus (SLE) have an increased association with atherosclerosis leading to higher cardiovascular mortality rates. Inflammation is a crucial link in the development of atherosclerosis and autoimmune disorders. Immune dysregulation in autoimmune diseases could contribute to the increased risk of atherosclerosis in these patients. Thus, immune modulation and anti-inflammatory treatments may help control the development of atherosclerosis in autoimmune disorders.

Major histocompatibility complex class I chain-related member A (MICA) encodes a stress-induced cellsurface glycoprotein that is expressed in keratinocytes, fibroblasts and gastrointestinal epithelium, among others. MICA is not associated with β2-microglobulin and does not appear to present peptides. MICA displays a high degree of allele polymorphism within the non-classical HLA gene loci. The functional significance of these polymorphisms is unknown, although certain changes in protein amino acid sequence cause an abnormal expression or affinity with NKG2D, its ligand on the surface of NK, γδ-T and CD8+ lymphocytes, affecting NK-cell activation and T-cell response modulation. Indeed, many tumoral cells express MICA on their surface, and circulating soluble MICA also triggers NKG2D downregulation and impairs lymphocyte cytotoxicity in tumoral escape. This demonstrates the therapeutic potential of anti-MICA antibodies to overcome immune suppression and trigger tumor destruction. MICA also affects organ transplants outcome, as MICA antigens elicit a very powerful antibody response in recipients of organ allografts. NKG2D ligand induction might also participate in the amplification loop that leads to tissue damage during acute graft vs. host disease. MICA is also an important candidate gene for a number of clinically significant diseases, including diabetes, rheumatoid arthritis, and other autoimmune diseases. This updated version of our previous review highlights the advantages and limitations of MICA gene studies in several pathologies and transplantation, and critically discusses the most recent and updated findings in this rapidly evolving field.