Am. J. Respir. Crit. Care Med., Vol 155, No. 4, 04 1997, 1453-1460.
Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones
K Kurosu, N Yumoto, M Furukawa, T Kuriyama and A Mikata
First Department of Pathology, School of Medicine, Chiba University, Chiba City, Japan.
We analyzed the third complementarity-determining region (CDR3) of the
immunoglobulin heavy chain (IgH) gene in five patients with lymphoid
interstitial pneumonia (LIP) through a two-step polymerase chain reaction
(PCR) and sequencing analysis. By sequencing analysis of the PCR products,
morphologic LIP could be divided into two groups: a polyclonal type and a
minor monoclonal type. Because of their high frequencies, minor monoclonal
clones seemed to be neoplastic clones hidden in normally reactive
lymphocyte clones. Consequently, only the polyclonal type might have
represented true LIP. Sequencing of the PCR products from open-chest biopsy
and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one
patient with minor monoclonal type LIP confirmed this possibility. In true
LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte
clones derived from fetal tissue. In three of these six clones, the
D-region (N-D-N) lengths were very short, whereas four clones showed a high
homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA
antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA
antibodies, and G6 are autoreactive antibodies, immature B cells stimulated
by autoantigens might play some role in the pathogenesis of true LIP.
