An elevated IgG4 response in chronic infectious aortitis is associated with aortic atherosclerosis

Abstract

Recently, it was shown that infectious bacterial aortitis can stimulate an elevated IgG4 + plasma cell response in the vessel wall, which could mimic IgG4 aortitis/periaortitis. However, the factors that are associated with an elevated IgG4 + plasma cell response in infectious aortitis are unclear. To ascertain these factors, 17 cases of infectious aortitis and 6 cases of non-infectious severe abdominal aortic atherosclerosis were assessed for the magnitude of IgG4 + plasma cell response. The degree of IgG4 + plasma cell infiltration was determined by immunohistochemistry. Infectious cases were subcharacterized as chronic (43 weeks duration) or acute ( o3 weeks duration) based on the duration of symptoms, and as involving either the ascending aorta or the distal aorta, ie, the descending thoracic and/or abdominal aorta. There was a 5-16-fold greater degree of IgG4 + plasma cell infiltration in the chronic distal infectious aortitis group compared with the other three infectious aortitis groups (P ≤ 0.0007), and compared with non-infectious severe abdominal aortic atherosclerosis (Po 0.0008). This resulted in a greater IgG4/IgG ratio in the chronic distal infectious aortitis group compared with the acute ascending and acute distal infectious aortitis groups (Po 0.03). The degree of IgG4 + plasma cell infiltration in chronic distal infectious aortitis overlaps with that seen in the aortitis and periaortitis of IgG4-related disease. In the chronic infectious aortitis cases, the degree of IgG4 + plasma cell infiltration was more intense in patients with moderate to severe aortic atherosclerosis compared with those patients with less aortic atherosclerosis (P = 0.007). These findings indicate that an elevated IgG4 + plasma cell response occurs in the descending thoracic and abdominal aorta in the setting of chronic bacterial infectious aortitis and pre-existing atherosclerosis. This inflammatory response to chronic infection in atherosclerosis-laden aortas may have implications for the development of IgG4-rich inflammatory atherosclerotic aortic aneurysms.

A strobe multicenter descriptive study of 55 infectious aortitis

“…These data stem from a series of 29 patients with IA, the largest before the year 2000. [1] Since then, numerous isolated case-reports or small series have been published and the reported germs are similar to what was described before 2000: 30 cases of S aureus ,[ 4 5 6 7 8 9 10 11 12 13 14 15 ] 72 Salmonella spp. ,[ 4 5 16 17 18 7 9 19 20 21 22 23 24 25 ] 16 Streptococcus spp.…”

“…,[ 4 5 16 17 18 7 9 19 20 21 22 23 24 25 ] 16 Streptococcus spp. ,[ 4 5 6 26 27 28 29 10 30 31 ] and 6 Clostridium septicum . [ 32 33 34 35 36 37 ]…”

Antibody Subclass and Glycosylation Shift Following Effective TB Treatment

“…IgG4 emerges through class-switch late in disease due to its distance on the human IgG locus, and with low Fc-receptor and complement affinity is selected under high antigen-burden when antibody titers are high. In diseases with prolonged antigen exposure and inflammation including parasitic infections ( 66 , 67 ), chronic Staphylococcus aureus ( S. aureus ) infection ( 68 ), chronic infectious aortitis ( 69 ), melanoma ( 57 ), and even following repeated high-antigen dose immunization ( 56 , 70 , 71 ) elevated IgG4 levels have been described. And in the wake of resolving antigen burden, a longitudinal analysis of patients chronically infected with Brugia malayi , demonstrated a rapid loss of IgG4 titers, and a preservation of IgG1 responses following treatment ( 67 ).…”

IgG4-related disease; a newly recognized entity with expanding spectrum

“…The involvement of the submandibular gland in IgG4RD occurs with the presentation of chronic sclerosing sialadenitis (9). IgG4RD's manifestation in blood vessels is seen as arteritis and two separate studies, one conducted by Siddiquee et al and the other by Tran et al showed the involvement of the aorta and the coronary arteries by the disease (11,14). In the setting of aortitis, the disease tends to occur mainly in the distal aorta on the background of chronic infectious aortitis and atherosclerosis (11).…”

“…Among such recently discovered rare entities is IgG4-related disease (IgG4RD) (1). A family of multi-systemic autoimmune diseases involves the vast parts of the human body, such as: the pancreas, kidneys, salivary glands, lungs, thyroid gland, biliary tree, mastoid bone, eyes, meninges, otorhinological organs, blood vessels, skin and the retroperitoneum (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). It is distinguished by the presence of IgG4 positive cells in body tissues and elevated serum levels of IgG and IgG4 along with a raised serum IgE and/or peripheral eosinophilia (1).…”