Maria G. Lazzaroni MD, Cecilia Nalli MD and Angela Tincani MD
Noel R. Rose BS AM MD PhD FCAP FAAAAI
Narin N. Carmel MD, Pnina Rotman-Pikielny MD, Alexey Lavrov MD and Yair Levy MD
Background: Vitamin D is a pivotal factor in calcium homeostasis and exerts immunomodulatory effects. Hypovitamin D has been demonstrated in systemic sclerosis (SSc) patients and may be related to more severe disease of longer duration and with extensive skin involvement.
Objectives: To seek anti-vitamin D antibodies in SSc patients, as found by previous research in patients with systemic lupus erythematosus (SLE).
Methods: The study included 54 SSc patients and 41 volunteers. Immunoglobulin (Ig) G and IgM autoantibody levels against 25(OH)D and 1,25(OH)D were obtained from patients and controls and compared. SSc patients were assessed for autoantibody profile and disease severity.
Results: Vitamin D antibodies were present in 87% of SSc patients and 42% of controls. Higher levels of anti-25(OH)D IgM antibodies were detected in SSc patients compared to controls (0.48 ± 0.22 vs. 0.29 ± 0.29, respectively, P = 0.002); however, IgG levels were lower in the SSc patients. No such discriminative effect was found regarding anti-1,25(OH)D antibodies between SSc and controls. No correlation was found between vitamin D antibodies and other autoantibodies, disease severity, or target organ damage.
Conclusions: To the best of our knowledge, this is the first study of these novel anti-vitamin D antibodies in SSc patients and the first time a correlation between IgM 25(OH) vitamin D antibodies and scleroderma has been identified. Further research on the pathophysiological significance and therapeutic potential of vitamin D is required.
Eleonora Ballanti MD, Maria Sole Chimenti MD PhD and Roberto Perricone MD
Systemic vasculitides are a group of uncommon diseases characterized by blood vessel inflammation. The complement system is involved in the pathogenesis and clinical manifestations of several autoimmune diseases, including systemic vasculitides. This enzymatic system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens, but research in recent years has demonstrated the important role that complement proteins play in modulating adaptive immunity and in bridging innate and adaptive responses. Its activation is also critical for the development of T cell immunity and natural antibodies as well as for the regulation of autoreactive B cells. In systemic vasculitides, particularly small-medium vessel vasculitides, the complement system has been shown to contribute to the development of inflammatory damage. In view of these crucial functions, the complement system represents an attractive therapeutic target for a wide range of diseases, including vasculitic disorders.
Luca Cantarini MD PhD, Giuseppe Lopalco MD, Marco Cattalini MD, Antonio Vitale MD, Mauro Galeazzi MD and Donato Rigante MD
Autoinflammatory and autoimmune disorders are characterized by chronic activation of the immune system, which leads to systemic self-directed inflammation in genetically predisposed individuals. Mutations in inflammasome-related proteins have been associated with autoinflammatory disorders, and the link between inflammasome and autoimmune disorders is becoming increasingly clear. As researchers learn more about these two areas, other disorders that were once thought to be autoimmune are now being considered autoinflammatory, or as having at least an autoinflammatory component. This review depicts the role of interleukin-1 as “Ariadne’s thread” on the path through the labyrinth of autoinflammatory and autoimmune disorders and emphasizes the blurred boundary between innate and adaptive immune systems.
Daphna Paran MD and Yaakov Naparstek MD
In the past decade we have witnessed a dramatic change in the management of autoimmune diseases, such as rheumatoid arthritis and spondyloarthropathies, due to the development of new biologic drugs designed to target key mediators in the autoimmune process. However, the development of similar target-specific drugs for the management of SLE has not been as successful. The B cell has long been considered central to the pathogenesis of SLE and has been regarded as an important target for biologic drugs. Several B cell-targeted drugs have been developed and although the mechanisms seem promising, most of the studies published to date have failed to achieve their primary endpoints, leading to an ongoing debate regarding the role of B cell therapy in SLE. The present report discusses the pros and cons of B cell-targeted therapy in SLE, reviews the clinical studies, and offers possible explanations for the discrepancies between randomized control studies and real-life experience.