Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease

Abstract

Molecular mimicry is a hallmark of the pathogenesis of rheumatic fever where the streptococcal group A carbohydrate epitope, N-acetyl glucosamine, and the a-helical coiled-coil streptococcal M protein structurally mimic cardiac myosin in the human disease, rheumatic carditis, and in animal models immunized with streptococcal M protein and cardiac myosin. Recent studies have unraveled the potential pathogenic mechanisms by which the immune response against the group A streptococcus attacks the rheumatic valve leading to chronic rheumatic heart disease. Both B- and T-cell responses are involved in the process, and evidence for the hypotheses of molecular mimicry and epitope spreading are reviewed.

Acute Rheumatic Fover: Modem Ethiopathogenetic Aspects

“…Кроме того, эти моноклональные антитела спо-собны связываться с эндотелием клапанов сердца, что ведет к экспрессии сосудистых молекул адге-зии-1 (VCAM-1). Последние стимулируют адге-зию Т-лимфоцитов к активированному эндотелию эндокарда с последующей их экстравазацией и проникновением в структуру клапана с развитием вальвулита [22,23].…”

Host–Pathogen Interactions in Streptococcal Immune Sequelae

“…Autoimmune responses against several host proteins such as cardiac myosin, heart valve glycoproteins and antigens of the sarcolemma membrane occur in ARF or RHD patients Goldstein et al, 1968;Guilherme et al, 2006;Tontsch et al, 2000;Wannamaker, 1973). Cross-reactivity of the autoantibodies with streptococcal cell wall carbohydrates, the cell membrane or the M protein was demonstrated (Kaplan and Suchy, 1964;Zabriskie and Freimer, 1966).…”

“…Moreover, the early processes in rheumatic carditis involve cellular immune responses. Elevated numbers of T-lymphocytes and macrophages occur in the cellular infiltrates that are observed in myocardial lesions of affected hearts (Cunningham, 2003;Guilherme et al, 2006;Roberts et al, 2001). The inflammation that takes place in those patients and is characterized by increased numbers of mature circulating T helper cells (CD4+ T-cells), elevated levels of cytokines such as IL-1 and IL-2, IFN, TNF-α and higher amounts of receptors for these cytokines .…”

“…Elevated titers of autoantibodies in the sera of ARF/RHD patients Dinkla et al, 2007;Dinkla et al, 2003;Guilherme et al, 2006) and deposition of immunoglobulin and complement in the affected hearts indicate that humoral immunity is crucially involved in ARF pathogenesis. Moreover, the early processes in rheumatic carditis involve cellular immune responses.…”

“…The molecular and immunological processes that drive the pathogenesis of this disorder and subsequent rheumatic heart disease (RHD) have been partially discovered. Cunningham, 2012;Dinkla et al, 2003;Guilherme et al, 2006;McCarty, 1956;Stollerman, 1969;Tontsch et al, 2000;Wannamaker, 1973). The diagnostic criteria for ARF are referred to as the major Jones criteria and include arthritis, erythema, carditis and neurological dysfunctions (chorea) (Keitzer, 2005).…”