Autoimmune diseases - New insights into a troublesome field

Abstract

Recent updates in the diagnosis and management of chronic inflammatory conditions can be brought together to better understand autoimmune diseases (ADs). With organ-specific or organ-limited and systemic ADs, physicians often are faced with a dilemma when making a diagnosis and may feel a kind of embarrassment when a more distinct nosological entity cannot be found. ADs often overlap with other diseases and good diagnostic procedures for ADs only become evidence-based when refined histopathologic, immunopathologic, and general laboratory analyses are available. Immunofluorescence analyses, Western blotting, CUT & RUN technology allow localization of the site of autoantibody-reactivity on the relevant DNA sequence. The Polymerase chain reaction technology and CRISPR-Cas9, the new gene editor using pools of synthetic non-coding RNAs in screening experiments, are expected to lead to advances in the diagnosis of ADs. The current use of mRNA as a vaccine against COVID-19 has increased confidence in the use of mRNA or long non-coding RNAs in the treatment strategy for ADs. The integration of new knowledge about innate immunity, the complement system, vaccinology, and senescence into the care of patients with ADs expands the therapeutic arsenal of disease-modifying drugs and allows for the repurposing of anti-cytokine monoclonal/biosimilar antibodies, originally designed for chronic inflammatory diseases, for ADs. This review article brings together some of the most relevant ideas; a case report included in this review highlights the difficulty of distinguishing between ADs, chronic inflammation, and/or granular disease.

Keywords: Biosimilars I; Complement; Cytokine; Innate immunity; Monoclonal antibodies.

Graphical abstract

Fig. 1

Innate Immunity and Autoimmune Diseases. The figure shows major innate immune players which (could) participate in ADs. The protein-oligomer inflammasomes are receptors/sensors that regulate the activation of caspase-1 (not shown) and induce inflammation in response to infectious microbes and molecules derived from host proteins - autoantigens. They have been implicated in chronic inflammatory disorders and other systemic ADs. The role of complosome – intracellular C components – is currently delved in more details.

Fig. 2

Routine laboratory test strategy to detect an autoimmune disease, (examples). AD (Autoimmune disease), IIF (indirect immunofluorescence), AAb-EIA (Autoantibody-enzyme-immuno-assay), ANA (Anti-nuclear antibodies), ACA (anti-cytoplasmic antibodies), AMA (Anti-mitochondrial antibody. panels a, b: ANA on HEp-2 cells (Euroimmun, Lübeck, Germany), images from laboratory Dr. Risch, SLE (Systemic lupus erythematosus), PBC (Primary biliary cholangitis).

Fig. 3

The complement system as part of a network mazing immunopathological events in ADs. It is evident, that C activation producing anaphylatoxins, C3a, C5a and the SC5b-9 complex will activate cytokine-producing cells hence becoming responsible, at least in part, for cytokine storm.

Fig. 4

This sketch displays the fast and efficient function of a potent vaccine based on liposome embedded mRNA. Such an approach shows promise in ADs as anticipated using a mouse model of multiple sclerosis [73]. Dendritic cells (see also Fig. 1) are antigen-presenting cells recognized by T helper cells. The figure inspires application of lnc_mRNA to treat ADs.

Fig. 5

Flow Chart Case Report of a case diagnosed for sarcoidosis type II; evolution over 7 years. Please note the instauration of an actual ADs therapeutic regimen for a non-ADs.

Fig. 6

Iconography of the Case Report from Fig. 5. In (A) retinal granuloma above the optic papilla. (Heidelberg retinal tomography). In (B) Raynaud phenomenon (right hand). In (C) thoracic CT cut displaying lymph node and lung participation of the sarcoidosis.