**Positron Emission Tomography in Autoimmune Disorders of the Central Nervous System**

Ara Kaprelyan

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40 Immunopathology and Immunomodulation

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61171

#### **Abstract**

This chapter covers the basic knowledge on interactions between the central nervous system and immunity. It presents information about the main factors and mecha‐ nisms that refer to the traditional and new concepts on immune privilege of the brain. In addition, the immune surveillance and tolerance are discussed in context of the central nervous system homeostasis, production of autoreactive lymphocytes, and neurons vulnerability.

Certain general aspects in principles of positron emission tomography (PET) techni‐ que, radiotracer characteristics, and specificities of the cerebral glucose uptake are provided. The chapter also offers an overview of the current clinical application of (18F)-FDG PET imaging in the detection and differential diagnosis of different auto‐ immune disorders of the central nervous system.

This chapter reviews the autoimmune underlying mechanisms and main abnormali‐ ties in cerebral glucose metabolism in patients with multiple sclerosis, late-onset atax‐ ias, and limbic encephalitis. Own clinical observations and results are presented in accordance to previous publications. Neuroimaging findings are discussed in context of PET sensitivity and accuracy for assessment of disease localization and characteri‐ zation.

**Keywords:** (18F)-FDG PET/CT, autoimmunity, CNS disorders

## **1. Introduction**

#### **1.1. Central nervous system and immunity**

Advances in scientific research and accumulated working knowledge of anatomo-functional subsystems of the central nervous system (CNS) and their relationship with the downregula‐

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tion of the immune system play a crucial role in the understanding of underlying mechanisms and treatment of immune-mediated neurological disorders [19, 37].

Traditionally, CNS is considered an immunologically-privileged site, meaning the brain and spinal cord can tolerate the introduction of foreign antigens without eliciting an afferent immune response [29, 34]. Immune privilege is believed to be an active process aiming to protect the brain structures from the harming effect of an inflammation. This immune privilege is thought to be due to a lack of lymphatic drainage and the integrity of blood-brain barrier (BBB) [21]. It varies throughout the different parts of the CNS, being most pointed in the white matter. Among the other factors that also contribute to the maintenance of brain immune privilege are local production of immunosuppressive cytokines, increased expression of surface molecules inhibiting complement activation, low expression of major histocompati‐ bility complex (MHC) class Ia molecules, presence of neuropeptides, etc. [26].

Over the last two decades the concept of CNS as an immunologically-privileged site has been reevaluated. Today, experimental and clinical data show evidence suggesting the presence of resident CNS macrophages known as microglia [42]. Although the separation and isolation of CNS from the peripheral immune cells throughout the BBB, certain unique interactions exist due to the sequestration of neuronal antigens in "partially" immune-privilege sites, presence of antigen determinants shared by the nervous and immune systems, and secretion of immunoregulatory mediators by specific nerve cells [19, 29, 34]. Nowadays, it is known that activated lymphocytes are able to pass through the BBB regardless of their antigen specificity, directed by cytokines and adhesion molecules that are expressed on the brain endothelial cells (ICAM-1, VCAM-1) [2]. Normally, MHC class 1 and class 2 molecules are minimally expressed in the CNS, but in pathology the expression induced by proinflammatory cytokines IFN-γ is much higher. Immune surveillance in the CNS is under strong control and its major role is to provide constancy of the homeostasis in relation to the raised vulnerability of the neurons [26].

Immune tolerance is known to protect normal tissues from immune damage by prevention of immune response against a particular antigen to which the human organism is normally responsive. In the past, it was thought that the break of immune tolerance causes the produc‐ tion of autoantibodies and/or sensitized cytotoxic T-lymphocytes, attacking own tissues, the so-called autoreactive lymphocytes. Today, it is evident that these autoreactive cells normally exist in the immune system in a state of anergy and areactivity toward own antigens. Respec‐ tively, the immune tolerance is considered as a result from suppression and elimination of autoreactive T-lymphocytes [2].

It is known that autoimmunity represents an abnormal immune response directed against the cells and tissues of the organism. Autoimmune responses are considered an integral part of the immune system and present a survival self-defense mechanism. It is postulated that this aberrant immune response refers to the development of different diseases. The mechanisms of autoimmune disorders of the CNS are associated with molecular mimicry, upregulation of heat shock proteins, the release of so-called "sequestrated" antigens (brain tissue antigens hidden behind the BBB), bystander activation, and production of neoantigens [13, 42]. Most commonly T- and B-cell mediated autoimmune diseases result from the elimination and inhibition of regulatory T-cells or the dysregulation of humoral immunity.
