Immuno-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, spondyloarthritis, and inflammatory bowel disease are characterised by pathophysiological mechanisms wherein the immune system erroneously targets the body's own tissues. This review explores the heightened vulnerability of women with IMIDs, influenced by hormonal modulators like estrogen and progesterone. The challenges this poses are multifaceted, encompassing the impact of active disease and medical treatments throughout life stages, including family planning, fertility, and menopause. From the perspectives of rheumatologists and gastroenterologists, we review current management strategies and underscore the need for a multidisciplinary and life-cycle approach to healthcare for women with IMIDs.

Metabolic syndrome poses a great worldwide threat to the health of the patients. Increased visceral adiposity is recognized as the main determinant of the detrimental clinical effects of insulin resistance. Inflammation and immune system activation in the adipose tissue (AT) have a central role in the pathophysiology of metabolic syndrome, but the mechanisms linking increased adiposity to immunity in the AT remain in part elusive. In this review, we support the central role of adipocyte overload and relative adipose failure as key determinants in triggering immune aggression to AT. This provides a mechanistic explanation of the relative metabolic wellness of metabolically normal obese people and the disruption in insulin signaling in metabolically obese lean people.

Molecular and cellular aspects of the autoimmune pathophysiology in SLE is linked to the “The causality principle”. SLE Classification Criteria identify per definition disease measures (here: synonymous with classification criteria), but not diagnostic criteria within a classical framework. These two mostly theoretical criteria collections represent a salient conflict between phenomenology and the causality principle – between disease measures and molecular interactions that promote such measures, in other words their cause(s). Essentially, each criterion evolves from immunogenic and inflammatory signals – some are interconnected, some are not. Disparate signals instigated by disparate causes. These may promote clinically heterogenous SLE cohorts with respect to organ affection, autoimmunity, and disease course. There is today no concise measures or arguments that settle whether SLE cohorts evolve from one decisive etiological factor (homogenous cohorts), or if disparate patho-biological factors promote SLE (heterogenous cohorts). Current SLE cohorts are not ideal substrates to serve as study objects if the research aims are to describe etiology, and molecular interactions that cause - and link - primary and secondary pathophysiological events together - events that account for early and progressive SLE. We have to develop SLE criteria allowing us to identify definable categories of SLE in order to describe etiology, pathophysiology and diagnostic criteria of delimitated SLE versions. In this regard, the causality principle is central to define dominant etiologies of individual SLE categories, and subsequent and consequent down-stream diagnostic disease measures. In this sense, we may whether we like it or not identify different SLE categories like “genuine SLE” and “SLE-like non-SLE” syndromes. Many aspects of this problem are thoroughly discussed in this study.

BackgroundComplement levels have been proposed as candidate biomarkers of disease activity and obstetric risk in systemic lupus erythematosus (SLE) pregnancies, but their reliability has been questioned due to the physiologic fluctuations of complement during gestation. Thus, this network meta-analysis aimed at assessing the clinical significance of complement fluctuations in lupus pregnant women. MethodsCorresponding authors of 19 studies meeting inclusion criteria were invited to contribute with additional data including C3 and C4 levels [before pregnancy, at conception, in every trimester (T) and 3 months after delivery]; data were pooled together in a network meta-analysis. ResultsA total of 532 lupus women from four studies were included in the analysis. In SLE women, C3 and C4 increased progressively during gestation: levels remained stable during T1 and peaked in T2 to decrease in T3. Patients with previous lupus nephritis (LN) and those who experienced flares during pregnancy had significantly lower mean levels of C3 and C4 at all timepoints. The lowest levels of complement were observed, particularly during T1, in patients with LN and gestational flare. Both reduction and the lack of increase of C3 and C4 levels at T1 versus conception were associated with gestational flares, particularly in LN patients. Pregnancies with flare had a statistically significant higher rate of maternal and fetal complications(60% versus 50.3%; p = 0.03). ConclusionsLow complement levels, particularly in T1, were associated with a higher frequency of gestational flare. Either reduction or smaller increase of C3 and/or C4 levels, even within normal range, might predict flares especially in early gestation.

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.