New insights into the taxonomy of autoimmune diseases based on polyautoimmunity

• Published in: Journal of autoimmunity Vol. 126; p. 102780
• Main Authors: Rojas, Manuel, Ramírez-Santana, Carolina, Acosta-Ampudia, Yeny, Monsalve, Diana M., Rodriguez-Jimenez, Mónica, Zapata, Elizabeth, Naranjo-Pulido, Angie, Suárez-Avellaneda, Ana, Ríos-Serna, Lady J., Prieto, Carolina, Zambrano-Romero, William, Valero, María Alejandra, Rodríguez, Yhojan, Mantilla, Rubén D., Zhu, Chengsong, Li, Quan-Zhen, Toro-Gutiérrez, Carlos Enrique, Tobón, Gabriel J., Anaya, Juan-Manuel
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2022
• Subjects: Autoantibodies; Autoimmune Diseases - complications; Autoimmune Diseases - diagnosis; Autoimmune Diseases - epidemiology; Autoimmune thyroid disease; Autoimmunity; Cross-Sectional Studies; Humans; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - epidemiology; Polyautoimmunity; Rheumatoid arthritis; Sjogren's Syndrome - complications; Sjogren's Syndrome - diagnosis; Sjogren's Syndrome - epidemiology; Sjögren's syndrome; Systemic lupus erythematosus; Systemic sclerosis; Taxonomy; Polyautoimmunity; Systemic lupus erythematosus; Taxonomy; Sjögren's syndrome; Rheumatoid arthritis; Systemic sclerosis; Autoimmune thyroid disease
• DOI: 10.1016/j.jaut.2021.102780
• ISSN: 0896-8411; 1095-9157

The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed “overt polyautoimmunity” (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as “latent PolyA”. We aimed to explore a new taxonomy of ADs based on PolyA. In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials. •Latent and overt polyautoimmunity (PolyA) are common in autoimmune diseases (ADs).•Latent and overt PolyA cluster together.•Autoimmune diseases can be classified according to PolyA.•Clusters of PolyA disclose differential clinical and immunological characteristics.