Elisabetta Borella

Autoantibodies in Polymyositis and Dermatomyositis

Inflammatory myopathies are a group of acquired diseases, characterized by immunoflogistic processes primarily involving the skeletal muscle. According to recent classification criteria, four major diseases have been identified: polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myositis (NAM). Autoantibodies can be found in the sera of most patients with myositis. Myositis-specific autoantibodies (MSAs) are markers of very specific disease entities within the spectrum of myositis, and target proteins involved in key processes of protein synthesis. Myositis autoantigens comprise the well-defined aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, and the signal recognition particle (SRP) ribonucleoprotein, together with novel targets such as TIF1-γ, MDA5, NXP2, SAE, and HMGCR. Recent studies suggest that autoantigens drive a B cell antigen-specific immune response in muscles. Interestingly, an increased expression of Jo-1 and Mi-2 in regenerating fibers in muscle biopsies from PM and DM patients compared to normal was demonstrated. Myositis autoantigen up-regulation was observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Non-immunological mechanisms seem to participate to the pathogenesis of inflammatory myopathies; induction of endoplasmic reticulum stress response in response to abnormal muscle regeneration and inflammation has recently been reported in patients with myositis. This review article provides an update of new emerging insights about the clinical and pathophysiologic role of principal autoantibodies in myositis.

Vitamin D: a new anti‐infective agent?

Before the antibiotic era, treatment of tuberculosis patients was restricted to sun exposure in sanatoria. Years later, it was found that 1,25‐dihydroxyvitamin D3 stimulates production of cathelicidins, a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes. Cathelicidins serve a critical role in innate immune defense, which plays an important role in the suppression of Mycobacterium infections and other pathogens. It is believed that the increased incidence of the common cold and pneumonia during winter is related, in part, to decreased exposure to sunlight, resulting in a decreased synthesis of 1,25‐dihydroxyvitamin D3. An association has been established between low levels of vitamin D and upper respiratory and enteric infections, pneumonia, otitis media, Clostridium infections, vaginosis, urinary tract infections, sepsis, influenza, dengue, hepatitis B, hepatitis C, and HIV infections. Accumulating evidence suggests that 1,25‐dihydroxyvitamin D3 exerts protective effects during infections by upregulating the expression of cathelicidin and β‐defensin 2 in phagocytes and epithelial cells. Vitamin D may be acting as a panaceal antibiotic agent and thus may be useful as an adjuvant therapy in diverse infections.

Clinical Guidelines and Definitions of Autoinflammatory Diseases: Contrasts and Comparisons with Autoimmunity— a Comprehensive Review

Autoinflammatory diseases (AIDs) and autoimmune diseases (ADs) are characterized by an aberrant chronic activation of the immune system which causes tissue inflammation and damage in genetically predisposed individuals. Pathogenetic mechanisms underlying this damage differ between these two types of diseases; in AIDs, the innate immune system is directly responsible for tissue inflammation, while in ADs it works by activating the adaptive immune system, which becomes the main effector of the inflammatory process. Despite the fact that AIDs have only been recently defined, they are older than ADs. The innate immune system is found in plants and animals, and it developed earlier than the adaptive immune system, which first appeared in jawed vertebrates. According to genetic background and clinical, serological, and radiological findings, AIDs and ADs might be considered as a single spectrum of disorders, with a wide range of manifestations. Indeed, autoinflammatory-like diseases have been reported in simple organisms such as Drosophila melanogaster and Caenorhabditis elegans. We analyzed here the main pathogenetic and clinical features of these two groups of diseases mostly dealing with their similarities and differences.

Bronchiolitis obliterans organizing pneumonia in patients with autoimmune rheumatic diseases.

Abstract Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to corticosteroids and an excellent prognosis. It can occur in association with a broad spectrum of clinical conditions or can be isolated, in this last case named cryptogenic organizing pneumonia. We searched for BOOP in patients with autoimmune rheumatic diseases (ARD) in the literature, and we found 32 well-documented cases. We reported here demographic features, manifestations, treatment and outcome of patients with BOOP associated with ARD. Notably, BOOP can be the presenting feature in some patients with ARD; thus, a close follow-up of patients with BOOP is recommended.

Lipid Replacement Therapy: Is it a New Approach in Patients with Chronic Fatigue Syndrome?

Lipid replacement therapy (LRT) is an anti-aging product which reverses age-related changes in the lipid composition of organ and tissue cells. Since membrane lipids oxidation seems to be involved in the pathogenesis of Chronic Fatigue Syndrome (CFS), their substitution with new lipids coming from dietary supplements is speculated to be effective in CFS. We have analyzed some of the most recent articles about the effects of LRT in fatigue, showing the evidences supporting this theory as well as alluding to the weak points of the studies.

Infections and Idiopathic Inflammatory Myopathies

Abstract Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of conditions characterized by muscle inflammation and a variety of extra-muscular features, including fever, weight loss, and immunologic abnormalities. The major categories of IIM are dermatomyositis, polymyositis, necrotizing immune-mediated myositis, and inclusion body myositis. The pathogenesis of IIM has not been completely elucidated, but there is evidence that environmental factors, including infectious agents, trigger an abnormal autoimmune response in genetically susceptible individuals, leading to organ damage. In this chapter, we discuss the role of infectious agents as initiating factors in disease induction. Experimental findings in animal models of infection-induced myositis and epidemiological studies of humans that support this hypothesis are summarized here. Finally, considering that infections and cancer are the most common causes of death and morbidity among patients with IIM, the increased risk of developing infections in these patients is also discussed.