Lehmann Hartwig W, Knöll Antje, Küster Rolf-Michael, Modrow Susanne
Rheumaklinik Bad Bramstedt, Bad Bramstedt, Germany.
Arthritis Rheum. 2003 Jun;48(6):1631-8. doi: 10.1002/art.10979.
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.
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.
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 low-degree 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.
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.
寻找细小病毒B19感染与青少年风湿性疾病相关性的进一步证据,并深入了解这些疾病的免疫发病机制。
分析74例风湿性疾病患儿的配对血清和滑液样本中病毒DNA含量以及针对B19病毒蛋白VP1、VP2和NS1的抗体。还分析了124例非炎性骨病或生长发育迟缓患儿的对照血清。通过聚合酶链反应(PCR)扩增病毒DNA序列并进行测定。通过吸附到蛋白A珠上从血清和滑液中分离IgG复合病毒。通过定量PCR对病毒基因组进行定量来确定游离病毒与免疫复合病毒颗粒的量。
74例患者中有26例(35%)血清(n = 22 [30%])和/或滑液(n = 16 [22%])中可检测到细小病毒B19 DNA,而124例对照血清中只有9例(7%)病毒DNA呈阳性(P < 0.0001)。46例患者(62%)血清中存在针对结构蛋白的IgG,表明曾感染过B19。在29例患者(39%)和27例对照(22%)的血清中检测到NS1特异性抗体(P < 0.001)。此外,3例患者(4%)出现VP2特异性IgM。15例患者的血清和滑液随访样本中可反复检测到病毒DNA。测序显示核苷酸变异程度较低,属于细小病毒B19基因型1的范围。血清和滑液样本中均存在不同量的免疫复合病毒。
细小病毒B19在风湿患儿的血清或滑液中经常被发现。这些患者中B19持续感染率显著高于年龄匹配的对照组。