Ricerc@Sapienza

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region.

Hashimoto's thyroiditis, characterized by thyroid-specific autoantibodies, is one of the commonest autoimmune disorders. Although the exact etiology has not been fully elucidated, Hashimoto's thyroiditis is related to an interaction among genetic elements, environmental factors and epigenetic influences. Cellular and humoral immunity play a key role in the development of the disease; thus, a T and B cells inflammatory infiltration is frequently found.

The role of the immune system in mediating cochleovestibular pathologies has received increasing attention in recent years. Autoimmune vertigo may be an invalidating condition and may worsen the quality of life of affected patients, especially in the cases of delayed diagnosis. Since the etiopathogenesis is still not clear, also the treatment is not yet completely delineated. According to the clinical presentation, autoimmune vertigo can present as an isolated disorder or in association with systemic autoimmune diseases.

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric.

The innate immune system may affect the function and survival of motor neurons in ALS by at least three mechanisms. First, there is evidence to suggest that aggregates of mutant SOD1—which is derived from microglial and astroglial cells—activate neighbouring microglia by binding to TLR2, TLR4, and CD14, and subsequently promote neuronal cell death [9]. Second, the release of pro- inflammatory cytokines may drive motor neuron damage. Third, although poorly understood, a mechanism has been suggested on the basis of the functional analysis of microglial cells that express mutant SOD1 [10].

The immune system seems to be involved in the pathogenesis of endometriosis. Peritoneal chronic inflammation is present and natural killer cells and macrophages abnormalities have been reported in women with the disease. Moreover, a higher production of serum autoantibodies has been found, which could be related to various factors; some still need to be clarified. The correlation between endometriosis and autoimmune diseases is still unclear with few and conflicting available data.

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies.

The human leukocyte antigen class I gene HLA-B27 is the strongest risk factor for ankylosing spondylitis (AS), a chronic inflammatory arthritic disorder. More recently, the Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and 2 genes have been identified by genome wide association studies (GWAS) as additional susceptibility factors. In the ER, these aminopeptidases trim the peptides to a length suitable to fit into the groove of the major histocompatibility complex (MHC) class I molecules.

Hashimoto’s thyroiditis (HT) may occur associated with celiac disease (CD). Regulatory B cells (Breg) subsets have been shown to
play a significant role in autoimmune processes. Therefore, we have characterized their distribution in the peripheral blood
obtained from 10 patients with isolated HT, 10 patients with HT+ CD, 9 patients with isolated CD, and 9 healthy donors (HD).
Th17 cells were significantly increased in patients with HT and in patients bearing both HT and CD, while patients with

Background: Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis.