The molecular subtypes of autoimmune diseases

Abstract

Autoimmune diseases (ADs) are characterized by their complexity and a wide range of clinical differences. Despite patients presenting with similar symptoms and disease patterns, their reactions to treatments may vary. The current approach of personalized medicine, which relies on molecular data, is seen as an effective method to address the variability in these diseases. This review examined the pathologic classification of ADs, such as multiple sclerosis and lupus nephritis, over time. Acknowledging the limitations inherent in pathologic classification, the focus shifted to molecular classification to achieve a deeper insight into disease heterogeneity. The study outlined the established methods and findings from the molecular classification of ADs, categorizing systemic lupus erythematosus (SLE) into four subtypes, inflammatory bowel disease (IBD) into two, rheumatoid arthritis (RA) into three, and multiple sclerosis (MS) into a single subtype. It was observed that the high inflammation subtype of IBD, the RA inflammation subtype, and the MS "inflammation & EGF" subtype share similarities. These subtypes all display a consistent pattern of inflammation that is primarily driven by the activation of the JAK-STAT pathway, with the effective drugs being those that target this signaling pathway. Additionally, by identifying markers that are uniquely associated with the various subtypes within the same disease, the study was able to describe the differences between subtypes in detail. The findings are expected to contribute to the development of personalized treatment plans for patients and establish a strong basis for tailored approaches to treating autoimmune diseases.

Keywords: Autoimmune diseases; Disease heterogeneity; Molecular subtype; Precision medicine.

Graphical abstract

Fig. 1

The pathological classification of MS and LN. The blue part represents MS, and the yellow part represents LN. MS: multiple sclerosis. LN: lupus nephritis. WHO: World Health Organization. NMSS: National Multiple Sclerosis Society Advisory Committee. ISKDC: the International Study of Kidney Diseases in Children. ISN/RPS: International Society of Nephrology/Renal Pathology Society.

Fig. 2

Common flow chart for subtype classification. The traditional subtype division procedure is divided into the following five steps. Step 1. Data Preprocessing: Perform data quality control and standardization; Step 2. Feature Matrix Generation: Choose crucial biomarkers for subtype classification; Step 3. Clustering: Employ clustering algorithms to determine distinct disease subtypes; Step 4. Subtype functional definition: Analyze the functions and heterogeneity of each subtype; Step 5. Classifier construction: Construct classifier models for precision medicine and drug response prediction.

Fig. 3

Summary of the biological conclusions of ADs subtypes research. The figure describes the biological characteristics of each disease subtype at the molecular, cellular, organ and other levels. The blue part represents SLE (A: Neutrophil subtype, B: Interferon subtype, C: Lymphocyte subtype, D: Plasma cell subtype). The green part represents IBD (E: High metabolism subtype, F: High inflammation subtype); The pink part represents RA (G: Inflammation subtype, H: Joint damage subtype, I: Neutrophil subtype); The yellow part represents MS (J: Inflammation & EGF).

Fig. 4

The common features of the three inflammation subtypes. The summary on the left depicts commonalities among similar subtypes based on markers. In the Venn diagram, green represents the High Inflammation subtype of Inflammatory Bowel Disease (IBD), pink represents the Inflammation subtype of Rheumatoid Arthritis (RA), and yellow represents the "Inflammation & EGF" subtype of Multiple Sclerosis (MS). On the right, the figure illustrates how Jakinibs block the release of inflammatory cytokines, such as interleukins and interferons, by acting on Janus kinase (JAK).