Elevated Serum Levels of IgG4 in Patients with Heart Failure with Reduced Ejection Fraction: A Prospective Controlled Study

Abstract

(1) Background: Immunoglobulin gamma subclass 4 (IgG4) is a serum protein belonging to the immunoglobulin superfamily. It has a central role in certain immune-mediated conditions defined as IgG4-related disease. There is a paucity of data regarding the potential association of IgG4 and cardiovascular diseases. Our aim is to study the serum levels of IgG4 in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM). (2) Methods: patients with ischemic and non-ischemic DCM were included in this study. Non-ischemic DCM was defined as a left ventricular ejection fraction (LVEF) < 40% without coronary artery disease (CAD). Ischemic DCM was defined as a LVEF < 40% and proven CAD. The serum concentrations of IgG4 were measured by turbidimetry. (3) Results: Overall 98 patients with cardiomyopathy had significantly higher levels of IgG4 compared with the control group (77.4 ± 64.0 vs. 50.3 ± 28.8 mg/dL, p < 0.01). Although there was no difference in the total IgG levels in patients with ischemic DCM, the serum concentrations of IgG4 were significantly higher than the corresponding values in the control group (89.8 ± 67.3 vs. 50.3 ± 28.8 mg/dL; interquartile ranges: 40.4–126.5 vs. 31.8–66.8 mg/dL, p < 0.01). This was altered by gender and smoking. (4) Conclusions: The patients with ischemic DCM had increased serum concentrations of IgG4. Future studies are warranted to explore the potential role of an IgG4-mediated process in patients with heart failure with reduced LVEF.

Mycobacterium avium subsp. paratuberculosis Antigens Elicit a Strong IgG4 Response in Patients with Multiple Sclerosis and Exacerbate Experimental Autoimmune Encephalomyelitis

“…In support of this hypothesis, we have detected IgG4 antibodies in serum of RR-MS patients (~50%) directed against MAP_HSP70 533-545 , particularly in patients with higher EDSS scores. Normally, IgG4 antibodies constitute around 5% of total IgG immunoglobulins [27]. The presence of IgG4 in RR-MS patients may be attributed to chronic exposure to MAP, primarily through the fecal-oral route.…”

Coronary artery involvement in a patient with IgG4-related disease

“…Unlike rheumatologic diseases like rheumatoid arthritis and lupus in which systemic inflammation accelerates atherosclerosis and subsequently stenosis in the coronary artery, IgG4-RD coronary artery stenosis is caused by infiltration of IgG4 positive plasma cells by a nonatherosclerotic mechanism [8] . Overexpression of anti-inflammatory cytokines such as transforming growth factor-β (TGF-β) and interleukin ten and T-helper type-2-related cytokines like interleukins 4, 5, and 13 could be associated with the formation of the fibrotic arterial lesions in IgG4-related immune reactions [7 , 10] .…”