Current Immunology Reviews (Discontinued) - Volume 9, Issue 1, 2013

Several viruses have been suspected of causing or triggering vasculitis, with hepatitis B virus-associated vasculitis (HBV–AV; formerly and more usually known as HBV-related polyarteritis nodosa) and hepatitis C virusassociated cryoglobulinemic vasculitis (HCV–ACV) having the best-demonstrated and confident proof for a causal link with viruses. Evidence for the implication of other viruses in the pathogenesis of other primary systemic vasculitides, like Kawasaki or Behcet’s diseases, remains weak or controversial. However, human immunodeficiency virus (HIV), erythrovirus B19, cytomegalovirus, varicella-zoster virus or human T-cell lymphotropic virus-1 can induce some forms of vasculitis, which are mainly localized. Treatment for all these virus-associated vasculitides should be two-pronged: one to clear or at least control the viral infection, possibly with antiviral drugs when available; the other to rapidly control the clinical manifestations. Management of this second concomitant therapy is delicate and can rely on plasma exchange to clear immune complexes in HBV–AV or rituximab in HCV–ACV. Sometimes therapy must initially include short courses of corticosteroids, and cytotoxic agents for the most severe cases, both of which are potentially deleterious because they can hamper virus clearance and delay seroconversion.

Primary Sjogren’s syndrome (pSS) is a systemic as well as an organ-specific autoimmune disease characterized by lymphocytic infiltration of the glandular epithelial tissue. SS patients have been reported to be at highest risk of developing lymphoproliferative neoplasms, when compared with patients with other rheumatoid diseases. Factors such as cytokine stimulation, environmental factors, viral infection and genetic events as well as vitamin deficiency may contribute to the development of lymphoma. Over the past few decades, numerous efforts have been made to assess the relationship between lymphoma and SS. These include epidemiological surveys, molecular biologic assessments of clonality and well-linked register cohort studies evaluating the predictive value of clinical, laboratory and histological findings. Nevertheless, the mechanisms and factors predictive of lymphoma development in pSS patients remain to be defined. This review summarizes updated knowledge on the incidence of and risk factors for lymphoma development in pSS patients, as well as discussing the most recent findings on the development and treatment of lymphoma in pSS patients and the possible mechanism of lymphoma development.

Leptin is a protein produced by adipocytes that acts in the brain to regulate appetite and energy expenditure according to the amount of energy stored in tissue. There are several molecules involved in the control of metabolism which play an important function in the regulation of immune responses. Among these molecules, leptin has been shown to significantly influence both innate and adaptive immune responses and also in pathological conditions. Leptin is the product of the ob gene and is mainly secreted by adipocytes, although it has also been shown to be produced by T and B lymphocytes, natural killer cells and monocytes. It is a cytokine similar in structure to interleukin 2, an important T-cell growth factor. Further, recent studies indicated that leptin leads to stat3 activation in the hypothalamus through its receptors. However, leptin deficiency may lead to immune dysfunction leading to impaired cell mediated immunity (CMI). Higher and lower circulating levels of leptin may also lead to autoimmune disorders and infectious diseases. We discuss here the influence of leptin on the innate and adaptive immune responses and production of pro-inflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.

Multiple Sclerosis (MS) is a heterogeneous disease of unknown etiology. The current hypothesis proposes a complex interplay between an environmental agent and the immune system that induces an abnormal response in genetically predisposed persons, leading to the autoimmune disease of MS. In recent decades the incidence and prevalence of MS seem to have increased, which may be better explained by environmental rather than genetic changes. Some infectious agents have been implicated as the possible culprits, as they could be involved in the appearance of autoreactive T cells against myelin using different mechanisms. Among microorganisms, certain bacteria, such as Chlamydia (Chlamydophila) pneumoniae have been suggested, but viruses have generally been associated with MS etiopathogenesis, with human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) being the best studied in recent years. Updating a previous review, we reanalyze the role of these microorganisms in MS etiology in detail and discuss the contributions of the hygiene hypothesis and environmental agents, both infectious and non-infectious, in the explanation of epidemiological changes in MS.

Antibody molecules, produced during the adaptive immune response, are involved in protection from all types of pathogens, including viruses, bacteria, fungi, and protozoa. Antibodies bind to their cognate antigen via their two Fab portions, but most of their biological functions are mediated by their Fc portion when they bind to specific Fc receptors (FcR) on the membrane of immune cells. Crosslinking of FcR on the surface of cells activates several effector functions. These effector functions are beneficial because they lead to destruction of pathogens. However, in some cases, antibodies can direct these effector functions against normal tissues and cause autoimmune diseases. In recent years, the interaction of IgG antibody molecules with Fcγ receptors has been analyzed in great detail and new clues on the way particular factors modulate the IgG-FcγR interaction have been elucidated. Some of these factors include the different IgG subclasses, and the glycosylation pattern of the antibody. In this review, we describe the main types of Fcγ receptors (FcγR), and our current view of how different IgG subclasses bind to different FcγR, to promote antimicrobial cell responses. In addition, novel clinical aspects of antibody-FcγR interaction, including non-antibody molecules that can bind FcγR, and glycosylation variants of antibodies that can bind different cell membrane receptors are discussed.