SANTIAGO, Chile—Children who can mount an immune response against parvovirus but who are unable to eliminate the infection are at increased risk for developing juvenile idiopathic arthritis (JIA), according to data reported by Benito González, MD, et al in The Journal of Rheumatology.1

"Since every form of juvenile rheumatoid disease can be triggered by parvovirus B19, possible infection with this virus should always be taken into account in such patients."—Susanne Modrow, MD.
"The conclusion of these observations is that patients with JIA show a higher viremia than healthy children, in agreement with the possibility that B19 may play a role in the pathogenesis of JIA," writes lead author Dr. González, with the immunology unit at Luis Calvo MacKenna Hospital, in Santiago, Chile.

Signs of persistent parvovirus found only in cases, not controls

Dr. González and colleagues examined antiparvovirus anti-B19 antibodies IgM and IgG and DNA in 50 patients (average age 9.6 years) with JIA and in 39 healthy controls (average age 7.8 years). Among the 50 JIA patients, 19 had systemic arthritis, 11 had oligoarticular arthritis, and 20 had polyarticular.

Thirty-two percent of patients and 43.5% of controls had similar rates of infection with B19, demonstrated by anti-B19 IgG. According to the investigators, "These results indicate that previous infection by parvovirus B19 in patients with JIA and normal controls is similar. This antibody prevalence in both groups is in a range that would be expected in children, since parvovirus B19 infection is known as one of the classic diseases of childhood."

Anti-B19 IgM, which typically develops during the second week after infection and may be detectable for 4 to 6 months, was found in 20% of cases but in none of the controls.

Polymerase chain reaction (PCR) detected parvovirus B19 DNA (the viral genome) in 48% of JIA patients but in none of the controls (P <.01). Ten percent of cases had both IgM and B19 DNA. The parvovirus B19 genome was detected with all types of JIA and was more prevalent in cases of clinically active JIA. "The detection of parvovirus DNA in 48% of the patients with JIA indicates that they have developed persistent B19 infection and are incapable of eliminating the virus," the authors write.

Dr. González says that the data support evidence from studies in adults with RA that link chronic arthritis to evidence of earlier B19 infection and B19 viral persistence. "Our work demonstrated a higher frequency of parvovirus B19 infection markers (DNA and IgM) in children with JIA than in the control group, and also that active JIA correlated with the persistence of parvovirus DNA but not with IgG antibodies to parvovirus. Our study confirms recent observations regarding a high prevalence of viral DNA in patients with JIA and a possible role of this infection in the pathogenesis of JIA," he concludes.

More research needed on juvenile arthritis and parvovirus

Susanne Modrow, MD, with the rheumatology clinic at Regensburg University, in Germany, told CIAOMed that this study demonstrates the need for more research on the causal association between parvovirus B19 infection and JIA in children.

"The association of parvovirus B19 and transient arthritis is well known in adults, particularly in adult women, but the fact that the infection may cause joint problems in children and adolescents has been neglected. Recently we and other [researchers] have shown that parvovirus B19 has a high potential to induce and trigger various autoimmune reactions, which may follow acute infection. In the majority of cases the symptoms that are associated with the autoimmune reactions are transient and result in the inflammation of one to a few joints which may last for some weeks. The symptoms are mainly evident during the period of virus production. Immune complexes between the virus and antiviral antibodies are involved in stimulation of both specific and unspecific immune reactions. Once the virus has been successfully eliminated, the symptoms generally cease. There are some children [who] are unable to eliminate the virus. In these cases the symptoms persist, and the inflammatory reactions may result in severe joint destruction," Dr. Modrow said.

Dr. Modrow added that studies of cellular immune reactions in children with long-lasting B19-associated arthritis are needed in order to understand the basis of viral persistence in patients with JIA. "As the majority of children do not develop JIA or other forms of autoimmune disease after parvovirus B19 infection, individual genetic factors seem to be very important. Since every form of juvenile rheumatoid disease can be triggered by parvovirus B19, possible infection with this virus should always be taken into account in such patients," she said.

Dr. Modrow also noted that a few reports have indicated that immunoglobulin therapy might help patients with chronic B19 infection and arthritis. She told CIAOMed that clinical aspects, diagnosis, and molecular biology of parvovirus infections will be the focus of the International Parvovirus Meeting, in September 2007, information for which is available at http://www.veterinaria.uniba.it/download/parvomeeting.html.

Reference

1. González B, Larrañaga C, León O, et al. Parvovirus B19 may have a role in the pathogenesis of juvenile idiopathic arthritis. J Rheumatol. 2007;34:1336-1340.