THE ROCKEFELLER UNIVERSITY

1230 YORK AVENUE NEW YORK,NY 10021

 

June 12, 1987

JOSHUA LEDERBERG

PRESIDENT

Dr. A. J. Pinching
Department of Immunology
St. Mary's Hospital
Medical School

London W2 1PG

England

Dear Dr. Pinching:

You must have had many communications about your group's
extraordinarily interesting paper on the association of Gc
with AIDS as published in The Lancet for May 2.

The association; if anything is so sharp as to raise
further questions about the possibility of different kinds of
artifact. In your sample you can account for 30% of AIDS with
the rare Gc 1f homozygote; but in San Francisco certainly a
very much larger fraction of the total homosexual population
is already infected: so much fewer than 30% of them can be 1f.
There remains the likelihood that Ge is influencing the pro-
gression from serotype-positive to clinical disease -- a
matter that I am sure you are investigating very diligently!
Of course all of these numbers could be very readily recon-
ciled if the Gc effect is to accelerate the manifestation of
AIDS; and your London population may be temporally closer to
its initiation than is the case in San Francisco (and the
African later).

I did have to raise one unlikely ,alternative, but one that
probably should be checked out explicitly: that the Gc 1f pheno-
type that you find in such strikingly large numbers among AIDS
patients is a phenocopy, namely that something in the AIDS
disease process itself is resulting in the misclassification
of Gc 1£. One could spin various hypotheses to account for
such a possibility but the easiest thing is to test it very
directly. To belabor the obvious, you could look at some sample
of your "1f homozygotes" among AIDS patients, to determine if
their uninfected immediate relatives show an appropriate dis-
tribution of the 1f marker. You have such a strong association
that even a handful of kindreds should be enough to corroborate
that the Gc 1f marker in AIDS patients is an uncomplicated
Dr. A. J. Pinching
June 12, 1987

-2-

legacy of inheritance of Gc 1f£ from their (almost always)
heterozygous parents. This can be tested either directly
in parents, or in a very reasonable way by the distribution
of Gc 1£ among their siblings.

In this country I am urging that very careful considera-
tion be given to Gc screening in connection with the various
other epidemiological studies that are being proposed.

Yours sincerely,

Qe 6 Sx
|

j)* Lederberg