Understanding the Role of Polyautoimmunity in Rheumatic Diseases

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An estimated 5 percent of the world’s population is diagnosed with one of a group of heterogeneous autoimmune rheumatic diseases (ARDs) including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren’s syndrome (SS). Not only do these diseases share mechanisms and risk factors, they are often comorbid conditions recognized as polyautoimmune (PolyA) manifestations of the same underlying dysfunction.

Patients with SLE are frequently positive for anti-rheumatoid factor (RF) and less often for anti-citrullinated protein antibodies associated with RA, although less than 10% are diagnosed with concomitant SLE/RA, known as rhupus. Another 10% of SLE patients are recognized to have antiphospholipid syndrome (APS) although up to 54% have been shown to carry antibodies. Other PolyA’s may include SLE/hypothyroidism, RA/autoimmune thyroid disease (AITD), and concomitant symptoms of SS with SLE, AITD, or systemic sclerosis (SSc).

According to studies by Gonzalez and colleagues (the most recent of which is published in the Journal of Autoimmunity)1 , 2 patterns of PolyA have emerged:

1) Overt PolyA, which reflects more than one well-defined ARD in a single patient, and
2) Latent PolyA, in which underlying patterns of autoantibodies are identified that do not correspond to the main diagnosis, and may be predictive of 1 or more additional ARDs.

The authors conducted a cross-sectional cluster analysis of patients with the most common ARDs for antibody and cytokine patterns in a cohort of 187 individuals with diagnoses of SLE, RA, SSc, and SS (n = 70, 51, 35, and 31). They found that the frequency of PolyA did not differ across all 4 ARDs, although SLE and SS were associated with a younger age of onset.

Rheumatoid factor and CCP3 were identified in 84.3% and76.5% of patients with RA, who also had the highest levels of Interleukin (IL)-6, interferon (IFN)-α, and IL-12/23p40 cytokines. Antinuclear antibodies (ANAs) were most prevalent in patients with SSc (97% positive) and SLE patients (71.4%), with distinctive patterns of additional antibodies and cytokines to each disease.

The study revealed six main PolyA clusters involving the 4 ARDs that may provide biomarkers useful for diagnosis of current disease as well as prediction of other ARDs over time. The authors suggested that particular attention should be paid to latent PolyA, and to the strong association of IL-12/23p40 to 3 of the 6 cluster groups.

REFERENCE

1. Molano-González N, Rojas M, Monsalve DM.  "Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity." J Autoimmun 2019;98:24-32.