Low-dose intravenous immunoglobulin (IVIg) in different immune-mediated conditions.

IVIg has been used for a long time as a replacement therapy for primary and secondary immunodeficiencies. Beside this supplementary role, when used at higher doses (i.e., 2 g/kg/monthly) it exerts an immunomodulatory role able to control multiple autoimmune and systemic inflammatory diseases. Several mechanisms of action have been described and hypothesized, nonetheless a synergistic action on the different component of the immune response seems to be crucial. The other side of the coin are the costs which showed an increase during the years due to the production of highly purified preparations which limit side reactions. This renders the product not easily accessible especially for low-income countries. Moreover, it is based on plasma donations that experienced a significant shrinkage after the COVID-19 pandemic and the consequences are still impactful. Due to the above-mentioned problems different authors tried to find out if a lower dosage of IVIg (< 2 g/kg/monthly) might exert an immunoregulatory role. In this review we aimed to summarize the current literature about a possible beneficial effect of a lower dosage of IVIg in multiple conditions that would help to treat a vast majority of patients. Even though in some cases (e.g., Kawasaki disease and immune thrombocytopenia) results are promising, for other conditions more research is needed.

Oxidative stress, mitochondrial dysfunction, and respiratory chain enzyme defects in inflammatory myopathies.

We investigated the relationship between oxidative stress and inflammatory myopathies. We searched in the current literature the role of mitochondria and respiratory chain defects as sources of oxidative stress and reactive oxygen species production that led to muscle weakness and fatigue. Different molecules and pathways contribute to redox milieu, reactive oxygen species generation, accumulation of misfolded and carbonylated proteins that lose their ability to fulfil cellular activities. Small peptides and physical techniques proved, in mice models, to reduce oxidative stress. We focused on inclusion body myositis, as a major expression of myopathy related to oxidative stress, where mitochondrial abnormalities are causative agents as well. We described the effect of physical exercise in inclusion body myositis that showed to increase strength and to reduce beta amyloid accumulation with subsequent improvement of the mitochondrial functions. We illustrated the influence of epigenetic control on the immune system by non-coding genetic material in the interaction between oxidative stress and inflammatory myopathies.

Alarmins in autoimmune diseases.

Alarmins are endogenous, constitutively expressed, chemotacting and immune activating proteins or peptides released because of non-programmed cell death (i.e. infections, trauma, etc). They are considered endogenous damage-associated molecular patterns (DAMPs), able to induce a sterile inflammation. In the last years, several studies highlighted a possible role of different alarmins in the pathogenesis of various autoimmune and immune-mediated diseases. We reviewed the relevant literature about this topic, for about 160 articles. Particularly, we focused on systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, idiopathic inflammatory myopathies, ANCA-associated vasculitides, Behçet's disease) and cutaneous organ-specific autoimmune diseases (vitiligo, psoriasis, alopecia, pemphigo). Finally, we discussed about future perspectives and potential therapeutic implications of alarmins in autoimmune diseases. In fact, identification of receptors and downstream signal transducers of alarmins may lead to the identification of antagonistic inhibitors and agonists, with the capacity to modulate alarmins-related pathways and potential therapeutic applicability.