Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

Abstract

Objective. To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases.Methods. Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG-complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR.Results. Twenty-six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n ‫؍‬ 22 [30%]) and/or the synovial fluid (n ‫؍‬ 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1-specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2-specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed lowdegree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples.Conclusion. Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age-matched controls.

Prevalence of parvovirus B19-specific antibodies and of viral DNA in patients with endogenous uveitis

“…These figures are similar to those from Cohen and Buckley, who reported a rate of 70-80% in a healthy population at an age of 40 years [2]. Similar frequencies have also been reported in children with rheumatic diseases [15].…”

“…Compared to a healthy population of young adults, with a seroprevalence of 22%, this is a remarkable difference [9,23]. Elevated prevalences of NS-1 antibodies were also found in patients with rheumatic PanU [2,9,22,23] [9,15]. It has been previously shown that antibodies against NS-1 are produced in long-standing or persistent infections with a higher incidence of infection of mainly non-permissive cells (thrombocytes and white blood cells), resulting in permanent destruction of these cells.…”

Simultaneous persistence of multiple genome variants of human parvovirus B19

“…Due to viral replication in the erythroid progenitor cells, severe or lifethreatening diseases can occur in immunocompromised patients and in individuals with shortened red cell survival (Brown et al, 1984;Kurtzman et al, 1988;Pattison et al, 1981;Public Health Laboratory Service, 1990;Skjöldebrand-Sparre et al, 2000). Besides the typical features, B19V is implicated in a wide spectrum of illnesses including neurological, cardiac, hepatic and rheumatological disorders (Broliden et al, 2006;Kerr et al, 2002;Lehmann et al, 2003;Young & Brown, 2004).…”

Phospholipase A2 Activity-Dependent Stimulation of Ca 2+ Entry by Human Parvovirus B19 Capsid Protein VP1

“…B19 is the causative agent of erythema infectiosum (fifth disease), hydrops fetalis, and transient aplastic anemia (1,86). Several studies disclosed an association between B19 and a variety of diseases (43,48,63,80), such as arthritis (56, 77), vasculitic syndromes (19, 24, 31, 80), hepatitis (27,36,38,75,85), and neurological disorders (2, 85). Specifically, B19 infections have been observed to be associated with acute and chronic myocarditis (13,16,30,44,53,(58)(59)(60)71).…”