Article

High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients

Karolinska University Hospital, Tukholma, Stockholm, Sweden
Journal of Clinical Virology (Impact Factor: 3.47). 06/2005; 33(1):71-4. DOI: 10.1016/j.jcv.2004.11.011
Source: PubMed

ABSTRACT Human parvovirus B19 (B19) polymerase chain reaction (PCR) is now a routine analysis and serves as a diagnostic marker as well as a complement or alternative to B19 serology. The clinical significance of a positive B19 DNA finding is however dependent on the type of tissue or body fluid analysed and of the immune status of the patient.
To analyse the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients.
Parvovirus B19 DNA was analysed in paired bone marrow and serum samples by nested PCR technique. Serum was also analysed for B19-specific IgG and IgM antibodies and the results were compared with clinical and epidemiological data.
B19 IgG was found in 41 of 50 patients (82%) whereas none was B19 IgM positive. The serologic evaluation showed that none of the patients had acute B19 infection. However, B19 DNA was detected by PCR in 13 of 50 (26%) bone marrow samples from these patients indicating a high frequency of persistent infection compared with previous reports of patient groups and healthy controls. In the study, 22 patients had rheumatoid arthritis (RA) and 7 of these RA patients were B19 DNA positive in bone marrow. Rheumatoid factor was positive in 4 of the 7 B19 DNA positive RA patients as compared with Rheumatoid factor positivity in all of the 15 B19 DNA negative RA patients. Erosive arthritis in X-ray was less common in the B19 DNA positive group than in the B19 DNA negative group. A high frequency of parvovirus B19 DNA was thus detected in bone marrow samples in rheumatic patients. The clinical data does not support a direct association between B19 PCR positivity and rheumatic disease manifestation. Therefore, the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients must be interpreted with caution.

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However, new variants were found: V9 was detected in 1998 in France, in serum of a child with aplastic crisis. This variant differed from the prototypic B19 sequences by ~10 %. In 2002 we found, persisting in skin of constitutionally healthy humans, DNA of another novel B19 variant, LaLi. Genetically this variant differed from both the prototypic sequences and the variant V9 also by ~10%. Simultaneously, B19 isolates with DNA sequences similar to LaLi were introduced by two other groups, in the USA and France. Based on phylogeny, a classification scheme based on three genotypes (B19 types 1-3) was proposed. Although the B19 virus is mainly transmitted via the respiratory route, blood and plasma-derived products contaminated with high levels of B19 DNA have also been shown to be infectious. The European Pharmacopoeia stipulates that, in Europe, from the beginning of 2004, plasma pools for manufacture must contain less than 104 IU/ml of B19 DNA. 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Lisäksi tarkastelimme uusien virustyyppien esiintyvyyttä suomalaisten verenluovuttajien keskuudessa seulomalla n. 140 000 luovuttajan näytteet: tästä joukosta löytyi ainoastaan tyyppiä 1. Toisin sanoen, vaikka tyypin 2 DNA:ta löytyi yleisesti terveiden henkilöiden ihonäytteistä, tyypin 2 virusta ei suomalaisten verenluovuttajien keskuudessa havaittu. Vertaillessamme B19-prototyypin ja uusien B19-tyyppien biologisia ominaisuuksia sekä infektiokykyä soluviljelmissä osoitimme, että myös uudet parvorokkovirustyypit ovat biologisesti aktiivisia, infektiokykyisiä viruksia. Lisäksi vertailimme tyyppien 1 ja 2 immunologiaa ja vasta-ainediagnostiikkaa: osoitimme että kumpaa tahansa virustyyppiä kohtaan muodostuneet vasta-aineet tunnistavat myös toisen virustyypin, ja näyttäisivät suojaavan kummankin virustyypin uusintainfektioilta.
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