Response to Letters by Reiff et al and Hadjiev and Mineva

Woo, Karen; Garg, Joy; Dilley, Ralph B.; Hye, Robert J.

doi:10.1161/strokeaha.110.590794

Cited by 1 publication

(1 citation statement)

References 2 publications

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“…Furthermore, Frostegård and co-workers have also shown that low levels of IgM anti-PC antibodies in patients with lupus correlate with occurrence of detectable atherosclerotic plaques by carotid ultrasound (Anania et al, 2010). Low levels of IgM anti-PC have also been associated with increased occurrence of stroke (Fiskesund et al, 2010), heart attack (Gronlund et al, 2009), and symptomatic atherosclerotic cardiovascular disease in men over 60 years of age (de Faire and Frostegard, 2009), as well as Alzheimer’s disease (Eriksson et al, 2010). Higher levels of IgM and IgG binding to oxidized LDL, a complex macromolecule that expresses the PC epitope, have been found to correlate with a lower burden of atherosclerosis, as measured by carotid artery intima-media thickness by ultrasound (Fukumoto et al, 2000; Karvonen et al, 2003).…”

Section: Human Natural Igm and Their Protective Propertiesmentioning

confidence: 99%

Protective Roles of Natural IgM Antibodies

Grönwall¹,

Vas²,

Silverman³

2012

Front. Immun.

291

259

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Antibodies are a vital part of the armamentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens and these contribute to the enhancement of primitive innate functions. This repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is required to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythematosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New and unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.

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