Inflammatory features, including symptoms, increased serum interleukin-6, and C-reactive protein, in IgG4-related vascular diseases

Abstract

Immunoglobulin (IgG) 4-related diseases (IgG4-RDs) are fibro-inflammatory conditions characterized by tumorous swelling and serum IgG4 levels. Intrapelvic IgG4-RD has been subclassified according to the localization site and aortic shape as IgG4-related aortic aneurysms (IgG4-AAs), periaortitis (IgG4-PA), and retroperitoneal fibrosis (IgG4-RF). The IgG4-AA pathogenesis would involve interleukin (IL)-6 upregulation, and Th2-predominant and Treg-activated immune conditions. We characterized the features of intrapelvic IgG4-RD lesions, including presence of vascular lesions. The clinical, serological, and pathological features, including cytokines concerning Th1/2 and Treg (IL-4, IL-6, IL-10, IL-13, and interferon-gamma) of patients with IgG4-AAs (n = 24), IgG4-PA (n = 8), and IgG4-RF (n = 10) were retrospectively compared. Clinical symptoms, such as low-grade fever, abdominal/lumber pain, and anemia, were frequently detected in IgG4-AAs but rarely in IgG4-RF. Serum IL-6 and C-reactive protein (CRP) were significantly higher in IgG4-AAs and IgG4-PA than in IgG4-RF. Pathologically, IL-6+ cells were more frequently detected in IgG4-PA and IgG4-AAs than in IgG4-RF. There were no noteworthy differences in the clinical complications, white blood cell counts, serum IgE, and serum and immunopositive cells of other cytokines between the subgroups. Among IgG4-AAs and IgG4-PA, serum IL-6 and IL-6+ cells correlated with CRP, aortic diameter, and periaortic fibrosis. IgG4-AA and IgG4-PA, but not IgG4-RF, were characterized by "inflammatory" features, such as increased CRP and serum/pathological IL-6, and clinical inflammatory symptoms; thus, IgG4-AA and IgG4-PA belong to the same group as IgG4-related vascular disease. High levels of CRP and IL-6 would be hallmarks of IgG4-related vascular disease.

PEGylated Liposomal Methyl Prednisolone Succinate does not Induce Infusion Reactions in Patients: A Correlation Between in Vitro Immunological and in Vivo Clinical Studies

“…Interleukin IL-6 is a primary mediator of both acute and chronic inflammation and is involved in the pathogenesis of many chronic inflammatory diseases [54,55]. It has been found that in some cases of IgG4 RSD, patients have elevated IL-6 levels [56,57] but that was not the case for the patient in our study. Moreover, the administration of NSSL-MPS decreased IL-6 to non-detectable levels even after 24 h, as seen previously in in vivo studies [27].…”

IgG4-related aortitis/periaortitis and periarteritis: a distinct spectrum of IgG4-related disease

“…[5,26,28,29]. It has been reported that higher level of CRP is a hallmark for detecting perivascular involvement in IgG4-RD [25,28]. The mechanism of CRP elevation in IgG4-related PAO/PA needs to be further elucidated.…”

“…Elevation of ESR and hsCRP was an indicator of vascular wall inflammation in large-vessel vasculitis, such as chronic periaortitis, TA, etc. [5,26,28,29]. It has been reported that higher level of CRP is a hallmark for detecting perivascular involvement in IgG4-RD [25,28].…”

“…IgG4-RD with PAO/PA might be a distinct spectrum of IgG4-RD, as it is characterized by prominent fibrosis, sparse lymphoplasmacytic infiltration, fewer extra-nodal germinal centers, and mildly elevated serum IgG1, IgG4, and IgE concentrations [5,28,34]. Recently, a pioneer approach to classifying IgG4-RD into proliferative subtype and fibrotic subtype was reported [35].…”

Clinical characteristics of IgG4-related retroperitoneal fibrosis versus idiopathic retroperitoneal fibrosis: a retrospective study of 132 patients

“…CD4 + T cells are abundant in IRPF biopsies [20], while in IgG4-related RPF they show a T-helper 2 (Th2)polarization [21]. Th2 cytokines such as interleukin-4 and interleukin-13 enhance the production of both IgG4 and IgE [22]. Additionally, Th2 cytokines may induce the enrichment of the IgG4 + plasma cell [23].…”