Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman's disease.
The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystemic disorder associated with osteosclerotic myeloma and multicentric Castleman's disease (MCD). Human herpesvirus type 8 (HHV-8) DNA sequences have been detected in lymph nodes of about 40% of human immunodeficiency virus (HIV)-negative patients with MCD, and in bone marrow stromal cells of patients with multiple myeloma. Considering these data, we investigated the presence of HHV-8 in 18 patients with POEMS syndrome (9 with MCD), by nested polymerase chain reaction (N-PCR) to detect DNA sequenses in various cells and tissues obtained by biopsy or at autopsy (13 patients, of whom 7 had MCD), and by an immunofluorescence assay to detect anti-HHV-8 IgG antibodies in blood (18 patients, of whom 9 had MCD). Detection of HHV-8 DNA was performed using three different N-PCR, targeting nonoverlapping regions in open reading frame (ORF) 25 and ORF26. Seven of 13 (54%) POEMS patients had HHV-8 DNA sequences in their tissues, as assessed by all three N-PCR, and 9 of 18 (50%) had circulating anti-HHV-8 antibodies. HHV-8 was mainly detected in the subset of POEMS patients with MCD (6 of 7 [85%] for DNA sequences; 7 of 9 [78%] for antibodies). The percentage of positive N-PCR was higher in lymph nodes than in bone marrow samples (P <.02). Sequencing of amplicons showed a homogeneous restricted variability in the ORF26 region, characteristic of the minority subgroup B defined by Zong, and responsible for isoleucine and glycine substitutions at amino acid positions 134 and 167. These findings strongly suggest an association of HHV-8 infection with POEMS syndrome-associated MCD.
Bélec
L
L
Groupe d'Etude et de Recherche sur le Nerf Et le Muscle (GERMEN, EA 2347), Faculté de Médecine de Créteil, Université Paris XII-Val de Marne, France.
Mohamed
A S
AS
Authier
F J
FJ
Hallouin
M C
MC
Soe
A M
AM
Cotigny
S
S
Gaulard
P
P
Gherardi
R K
RK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood; D005871:Castleman Disease / Q000097:blood / Q000150:complications* / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006566:Herpesviridae Infections / Q000097:blood / Q000150:complications*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D016878:POEMS Syndrome / Q000097:blood / Q000821:virology*; D016415:Sequence Alignment
D000914:Antibodies, Viral; D004279:DNA, Viral