Serum Organ-Specific Anti-Heart and Anti-Intercalated Disk Autoantibodies as New Autoimmune Markers of Cardiac Involvement in Systemic Sclerosis: Frequency, Clinical and Prognostic Correlates

Abstract

Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts of AHA and AIDA in SSc. Methods: The study included consecutive SSc patients (n = 116, aged 53 ± 13 years, 83.6% females, median disease duration 7 years) with clinically suspected heart involvement (symptoms, abnormal ECG, abnormal troponin I or natriuretic peptides, and abnormal echocardiography). All SSc patients underwent CMR. Serum AHA and AIDA were measured by indirect immunofluorescence in SSc and in control groups of non-inflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141), and normal blood donors (NBD) (n = 270). AHA and AIDA status in SSc was correlated with baseline clinical, diagnostic features, and outcome. Results: The frequency of AHA was higher in SSc (57/116, 49%, p < 0.00001) than in NICD (2/160, 1%), IHF (2/141, 1%), or NBD (7/270, 2.5%). The frequency of AIDA was higher (65/116, 56%, p < 0.00001) in SSc than in NICD (6/160, 3.75%), IHF (3/141, 2%), or NBD (1/270, 0.37%). AHAs were associated with interstitial lung disease (p = 0.04), history of chest pain (p = 0.026), abnormal troponin (p = 0.006), AIDA (p = 0.000), and current immunosuppression (p = 0.01). AHAs were associated with death (p = 0.02) and overall cardiac events during follow-up (p = 0.017). Conclusions: The high frequencies of AHA and AIDA suggest a high burden of underdiagnosed autoimmune HInv in SSc. In keeping with the negative prognostic impact of HInv in SSc, AHAs were associated with dismal prognosis.

A Machine-Learning Model for the Prognostic Role of C-Reactive Protein in Myocarditis

“…Conversely, we found lower CRP levels among patients with biopsy-proven myocarditis, arrhythmic presentation, more advanced NYHA class at presentation and a higher likelihood of AHA positivity. This suggests that in myocarditis autoimmune features are associated with a worse disease course [ 2 , 31 , 32 , 33 ], as recently shown by our group [ 34 ]. A role of innate immunity, i.e., the inflammasome, in the development of myocarditis has been suggested [ 35 ], leading to proposing a role for anti-interleukin-1 treatment.…”

“…In keeping with the worse outcome in autoimmune myocarditis, in this study and in another recent publication from our group [ 34 ] we found a prognostic role of anti-nuclear autoantibodies. In another recent study on systemic cutaneous sclerosis, we found that serum AHA were associated with cardiac involvement and increased risk of cardiac death [ 33 ].…”

Personalized Management of Myocarditis and Inflammatory Cardiomyopathy in Clinical Practice

“…Organ-and disease-specific serum AHA or anti-intercalated disk autoantibodies (AIDA) suggest isolated autoimmune or immune-mediated myocarditis in the context of SIDs [3,40,41]. The measurement of serum AHA and/or AIDA of IgG class should be utilized to identify patients that can especially benefit from immunosuppression [14].…”

Consensus on the assessment of systemic sclerosis–associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment

“…Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by vasculopathy, inflammation/autoimmunity and fibrosis 1–3 that may affect different organs and at different times during the disease evolution, resulting in heterogeneous clinical scenarios. Cardiac involvement in SSc is frequently referred to as “the silent killer.” In the EUSTAR cohort study from Elhai et al, 4 SSc primary heart involvement (SSc-pHI) was deemed to be the cause of 12% of SSc-related deaths.…”