Antibodies to parvovirus B19 non‐structural protein are associated with chronic but not acute arthritis following B19 infection

Kerr, Jonathan; Cunniffe, V. S.

doi:10.1093/rheumatology/39.8.903

Cited by 49 publications

(46 citation statements)

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“…This antibody prevalence in both the patient and the control group is in a range that would be expected in children and adolescents, since parvovirus B19 infection is known as one of the classic diseases of childhood (26). However, the frequency of NS1-specific IgG antibodies differed significantly, being present in 29 patients (39%) and 27 controls (22%) (P Ͻ 0.001); the frequency obtained in the control group is in accordance with the values described for the detection of NS1-specific IgG in individuals with past B19 infection (18,19,27). Western blot analysis of the synovial fluid samples derived from the arthritis patients revealed an antibody pattern that was qualitatively identical to that obtained from the sera (data not shown).…”

Section: Resultssupporting

confidence: 80%

“…B19 viremia usually reaches a peak at days 7-9 after infection and is resolved by the development of an IgM-and IgG-antibody response starting a few days later. Despite the development and presence of B19-specific immune reactions, ϳ20% of all B19 infections show a prolonged state of viremia or viral persistence restricted to the synovial fluid, and viral genomes are detected in bone marrow or other organs, e.g., synovial tissue, liver, or myocardium, for several years after infection (4,8,12,13,19,27,(29)(30)(31)(32)(33). Compared with our age-matched control group and compared with healthy adult blood donors, who have been shown to contain B19 DNA in 7% and in 0.1% up to 0.6% of cases, respectively (34)(35)(36), viral genomes were detected in 35% of arthritis patients in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown to be involved in the transactivation of the viral promoter and in the induction of apoptotic processes (14)(15)(16). NS1-specific antibodies were found preferentially in patients with prolonged B19 viremia and persistent infection (17)(18)(19)(20)(21).…”

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confidence: 99%

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

Lehmann¹,

Knöll²,

Küster³

et al. 2003

Arthritis & Rheumatism

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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.

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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

Lehmann¹,

Knöll²,

Küster³

et al. 2003

Arthritis & Rheumatism

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“…CFS is recognized to be an inflammatory disease which can persist for many years. Our findings are consistent with a previous study which reported that 73 % of NS1 antibody-positive CFS patients suffered arthralgia (Kerr & Cunniffe, 2000).Of the 83 patients with antibodies to B19 NS1, 61 (73 %) suffered from chronic arthralgia. This is similar to the results of previous studies of B19-infected patients (Kerr & Cunniffe, 2000).…”

supporting

confidence: 93%

“…Usually, the synthesis of these NS1 antibodies follows anti-VP1/VP2-IgG and starts at about 3-4 weeks after infection (Hemauer et al, 2000;von Poblotzki et al, 1995a). NS1 antibodies have been reported to occur in more severe and persistent courses of B19 infection (von Poblotzki et al, 1995a, b) and one study reports their association with chronic but not acute arthritis attributable to B19 infection (Kerr & Cunniffe, 2000). Therefore, their presence in 41.5 % of CFS patients as compared with 7 % of normal controls in the present study may indicate a more severe or persistent course of B19 infection in the context of CFS, whether or not B19 virus infection was the inducing event for CFS.…”

Section: Discussionmentioning

confidence: 99%

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Kerr

Gough

Richards

et al. 2009

Journal of General Virology

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(by real-time PCR). CFS/ME patients and normal blood donors had a similar B19 seroprevalence (75 % versus 78 %, respectively). Eighty-three CFS patients (41.5 %) as compared with fourteen (7 %) normal blood donors tested positive for anti-B19 NS1 IgG (x 2 564.8; P,0.0001; odds ratio59. 42,. Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR (x 2 59.35, P,0.002). Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA. As NS1 antibodies are thought to indicate chronic or severe courses of B19 infection, these findings suggest that although the seroprevalence of B19 in CFS patients is similar to controls, the immune control of the virus in these patients may not be efficient. INTRODUCTIONChronic fatigue syndrome/myalgic encephalomyelitis (CFS/ ME) is a disease characterized by severe and debilitating fatigue, sleep abnormalities, impaired memory and concentration, and musculoskeletal pain (Fukuda et al., 1994). In the Western world, the population prevalence is estimated to be of the order of 0.5 % (Report of the CFS/ ME Working Group, 2002;Papanicolaou et al., 2004). Several factors have been proposed to account for the pathogenesis of CFS; however, the most widely believed theory is that the symptoms of this disease are mediated by immune mechanisms which, in turn, may be somehow induced by virus infection (Komaroff & Buchwald, 1998;Devanur & Kerr, 2006).Human parvovirus B19 (B19) is the aetiological agent of the rash illness erythema infectiosum, arthralgia and arthritis, transient aplastic crisis in patients with shortened red cell survival, fetal death and pure red cell aplasia in immunocompromised persons (Kerr & Modrow, 2006). B19 infection has also been shown to occur just prior to the onset of symptoms of CFS in several case reports and follow-up studies (Kerr et al., 2002). However, B19 seroprevalence in CFS patients is similar to that in the general population. The B19 genome consists of a linear, single-stranded DNA of~5.6 kb, encoding the two capsid proteins VP1 and VP2 from the right side and the non-structural protein (NS1) from the left side (Astell et al., 1997). The NS1 protein possesses DNA-nicking and helicase activities, is cytotoxic and trans-activates the human interleukin-6 gene (Moffatt et al., 1996). Immunity to B19 virus is mediated by both humoral and cellular means. Antibodies to NS1 occur in approximately 30 % of infected individuals and may indicate more persistent and severe courses of B19 infection (Searle et al., 1998).The present study was undertaken in view of the paucity of knowledge of the role of B19 infection in CFS patients and the human immune response to it. Findings of this study confirm that B19 seroprevalence in CFS patients is similar to that in the normal population. However, antibodies to the NS1 protein were elevated in frequency in CFS patients and were associat...

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Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection

Landenberg¹,

Lehmann²,

Knöll³

et al. 2003

Arthritis & Rheumatism

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Objective. To show a possible association between parvovirus B19 infection and the presence of antiphospholipid antibodies (aPL) in patients with rheumatic diseases.Methods. Serum samples obtained from 88 children with various forms of juvenile rheumatic disease and from 40 adults with systemic lupus erythematosus, the antiphospholipid syndrome, or other rheumatic disease, who had previously been tested and shown to be positive for IgG aPL, were analyzed for the presence of B19 DNA, for antibodies against the B19 viral proteins VP1, VP2, and NS1, and for IgG aPL (anticardiolipin, anti-␤ 2 -glycoprotein I, and antiphosphatidylserine). As controls, serum samples obtained from 135 children with noninflammatory bone diseases or growth retardation were also analyzed.Results

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Antibodies to parvovirus B19 non‐structural protein are associated with chronic but not acute arthritis following B19 infection

Abstract: Antibodies to parvovirus B19 NS1 protein are associated with chronic but not with acute arthritis after B19 infection.

Cited by 49 publications

References 16 publications

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

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

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection

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