Serum Anti-Heart and Anti-Intercalated Disk Autoantibodies: Novel Autoimmune Markers in Cardiac Sarcoidosis

Abstract

Background: Sarcoidosis is an immune-mediated disease. Cardiac involvement, a granulomatous form of myocarditis, is under-recognized and prognostically relevant. Anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in nonsarcoidosis myocarditis forms. Objective: The aim was to assess serum AHAs and AIDAs as autoimmune markers in cardiac sarcoidosis. Methods: This is a cross-sectional study on AHA and AIDA frequency in: 29 patients (aged 46 ± 12, 20 male) with biopsy-proven extracardiac sarcoidosis and biopsy-proven or clinically suspected and confirmed by 18-fluorodeoxyglucose positron emission tomography and/or cardiovascular magnetic resonance (CMR) cardiac involvement; 30 patients (aged 44 ± 11, 12 male) with biopsy-proven extracardiac sarcoidosis without cardiac involvement (no cardiac symptoms, normal 12-lead electrocardiogram, echocardiography and CMR), and control patients with noninflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141) and normal blood donors (NBDs) (n = 270). Sarcoidosis patients were recruited in two recruiting tertiary centers in the USA and Italy. AHAs and AIDAs were detected by indirect immunofluorescence on the human myocardium and skeletal muscle. Results: AHA and AIDA frequencies were higher in sarcoidosis with cardiac involvement (86%; 62%) than in sarcoidosis without cardiac involvement (0%; 0%), NICD (8%; 4%), IHF (7%; 2%) and NBD (9%; 0%) (p = 0.0001; p = 0.0001, respectively). Sensitivity and specificity for cardiac sarcoidosis were 86% and 92% for positive AHAs and 62% and 98% for positive AIDAs, respectively. AIDAs in cardiac sarcoidosis were associated with a higher number of involved organs (p = 0.04). Conclusions: Serum AHAs and AIDAs provide novel noninvasive diagnostic autoimmune markers for cardiac sarcoidosis.

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

“…Representative examples of organ-specific AHA and AIDA patterns are shown in Figure 1. The AHA patterns have been previously described [21][22][23][24][25]30]. As shown in Figure 1, organ-specific AHA provided diffuse cytoplasmic staining with or without additional fine striational staining of atrial myocytes but were negative on skeletal muscle.…”

“…An additional positive control serum was titrated in order to assess reproducibility. End point titres for this serum were reproducible within one double dilution in all assays [21][22][23][24][25]30]. The frequency of AHA and of AIDA in SSc was compared with that observed in previously established control groups of non-inflammatory cardiac disease (NICD) (n = 160, 80 male, aged 37 ± 17 years, of whom n = 55 with other rheumaticrelated heart diseases without myocarditis, n = 67 hypertrophic cardiomyopathy, and n= 38 congenital defects), ischemic heart disease (n = 141, 131 male, aged 44 ± 14 years), and normal individuals (n = 270, 123 male, age 35 ± 11) [21][22][23][24]29].…”

“…AHA and AIDA were detected by indirect immunofluorescence (IF) at 1/10 dilution on 4 µm thick unfixed fresh frozen cryostat sections of blood group O normal human atrium and skeletal muscle [21][22][23][24][25]30]. Two sera were used as standard positive and negative controls and titrated in every assay.…”

“…The frequency of AHA and of AIDA in SSc was compared with that observed in previously established control groups of non-inflammatory cardiac disease (NICD) (n = 160, 80 male, aged 37 ± 17 years, of whom n = 55 with other rheumaticrelated heart diseases without myocarditis, n = 67 hypertrophic cardiomyopathy, and n= 38 congenital defects), ischemic heart disease (n = 141, 131 male, aged 44 ± 14 years), and normal individuals (n = 270, 123 male, age 35 ± 11) [21][22][23][24]29]. These control sera were obtained with informed consent from patients admitted to the hospital and were tested blindly from diagnosis at the time of description and validation of the IF assay [21][22][23][24][25]30].…”

“…They identify patients and symptom-free relatives at risk of disease progression but are very uncommon in other non-immune-mediated cardiac diseases, including coronary artery disease, or in normal subjects [12,[21][22][23][24]. In addition, we have recently reported a high frequency and high specificity of AHA and AIDA for cardiac involvement in sarcoidosis [25].…”