Interferon-Inducible Lfi202 Implicated as Candidate Gene for Lupus

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Interferon-Inducible Lfi202 Implicated as Candidate Gene for Lupus

WESTPORT, CT (Reuters Health) Sept 26 - A gene whose expression is induced

by interferon in mouse spleen is implicated as a susceptibility gene for

systemic lupus erythematosus (SLE), investigators report.

A locus on distal chromosome 1, dubbed Nba2, has previously been linked to

disease susceptibility in New Zealand black mice that develop SLE. In the

current study, Dr. L. Kotzin, of the University of Colorado Health

Sciences Center in Denver and colleagues studied that bred mice congenic for

the Nba2 locus.

These mice developed elevated serum levels of IgG antinuclear antibodies,

along with severe proteinuria that led to death from lupus nephritis, the

investigators report in the September issue of Immunity.

Microarray analysis of 11,000 genes revealed only two genes that differed in

expression between these mice and nonautoimmune control mice. Spleen cells

from the lupus mice expressed high levels of the gene lfi202 and low levels

of lfi203, opposite the pattern observed in control mouse cells. Both genes

reside within the Nba2 region.

Expression of lfi203 is believed to be reciprocal to expression of lfi202.

The increased expression of lfi202 was due primarily to increased expression

in B cells and non-B/non-T cells.

The investigators note that a homologous segment on human chromosome 1

includes three structurally related genes that colocalize with

lupus-susceptibility loci mapped in genome scans of SLE families. The

investigators suggest that expression of the lfi202 gene inhibits B-cell

apoptosis, leading to the enhanced lupus susceptibility.

Immunity 2001;15:435-443.