Generalized Wegener's granulomatosis in an immunocompetent adult after cytomegalovirus mononucleosis and bacterial urinary tract infection

Abstract

Human cytomegalovirus (HCMV) is frequently detected in autoimmune diseases, but its role in such disorders is poorly understood. Herein we describe the case of a young woman who developed generalized Wegener's granulomatosis (WG) after HCMV mononucleosis and urinary tract infection. During mononucleosis, the patient had extraordinarily high plasma levels of proinflammatory cytokines such as interleukin-5 and lymphotoxin ␣, autoantibodies, and a higher blood level of viral DNA than were found in other immunocompetent patients infected with HCMV or healthy controls. Active HCMV replication was detected after the onset of vasculitis, and HCMV genomes or antigens were found in blood, urine, and inflammatory lesions on the kidney. Thus, HCMV may have triggered or exacerbated inflammation and autoimmunity in this case of WG.

Cytomegalovirus-induced immunopathology and its clinical consequences

“…Autoimmune phenomena are common in CMV-infected patients, and various autoantibodies have been detected in patients with systemic CMV infection [32-34,36,37,42]. Nonspecific hyperactivation of humoral immunity can impede the development of specific B cell responses-a potential mechanism of viral immune evasion.…”

“…In solid organ transplant recipients, non-organ-specific autoantibodies, such as anti-endothelial cell, anti-smooth muscle cell, and anti-nucleus antibodies, are associated with CMV infection [36,37], likely increasing the risk for humoral and chronic allograft rejection [38,39]. In addition, hypergammaglobulinemia, cryoglobulinemia, and autoantibody production are features of CMV-induced mononucleosis and postperfusion syndrome [40-42]. …”

“…This patient had extraordinarily high plasma levels of IL-5 and lymphotoxin-α and developed autoantibodies, concomitant with the primary CMV infection. After the onset of vasculitis, CMV genomes were detected in the blood and urine, and CMV antigens were observed in inflammatory lesions of the kidney, suggesting that CMV triggers and maintains the autoimmune process [42]. …”

“…In such disorders, CMV infection coincides with the onset of inflammatory disease [42-45], as discussed, or with the initiation of immunosuppressive therapy [81]. Recently, IgM antibodies against CMV were observed more frequently in patients with c-ANCA-positive vasculitis compared with controls, while no other viral, bacterial and parasitic infections appeared to be involved [82].…”

High TNF-alpha and IL-8 levels predict low blood dendritic cell counts in primary cytomegalovirus infection

“…The cytokine levels for 11 of 14 CMV-infected patients and 10 of 14 controls have been previously reported. 9 Due to the nonparametricity of the experimental data, the significance between patients and controls for selected variables, such as viral load, DC frequency, and cytokine levels, was determined by Wilcoxon rank sum test. A p value of .05 or less was considered significant.…”