b. The genes determining LW activity are not part of the Rh system. Genetic
independence has been shown in families whose LW─negative trait segregates
separately from the Rh genes. Phenotypically, however, the gene products are related.
This is confirmed both through the original observation that LW activity is always weak
in adult Rh-negative cells, and more conclusively, through observation that all the rare
persons who lack Rh activity of any kind also lack LW activity. The basis for this
interaction is not clear. The LW gene appears to require, for its expression, some
product of Rh gene activity.
c. The clinical significance of LW is that there are persons with cells that are
LW-variant and these persons can produce anti-LW. If they are Rh-positive but
LW-negative, the resulting antibody may appear to be anti-Rho(D) occurring in an
Rh-positive. Anti-LW activity has been document as an autoantibody, and possibly as
part of early development of anti-Rho(D).
2-23. Rhnull SYNDROME
a. At least 22 persons have been found, in 14 families, whose cells have no Rh
antigens at all. Numerous elegant studies have revealed that at least two genetic
mechanisms may produce this phenotype. Most such individuals possess perfectly
normal Rh genes whose expression seems to be blocked if an independently
segregating gene is present in homozygous state. The term regulator type of Rhnull is
applied to this event. It appears that before Rh genes can act, some action must be
taken by a very common gene referred to as X1r. Homozygotes for the very rare
amorphic allele Xor are unable to express the activity of Rh genes. The parents and
offspring of such individuals have normal Rh genotypes; in some cases, overall Rh
reactivity is depressed, a finding consistent with heterozygosity for an amorphic
regulator gene. Thus, Rhnull persons of the regulator type have normal Rh genes which
are unable to function. These persons transmit normal Rh genes to their offspring, in a
manner analogous to the transmission of A or B genes by someone of the Bombay
b. Rarer still is the Rhnull phenotype in persons homozygous for an amorphic
gene at the Rh locus. The homozygote is unable to manufacture any Rh antigens. The
parents and offspring all possess a single dose of the amorphic gene, so each presents
a phenotype with only one set of Rh antigens.
c. Whatever the genetic cause, red blood cells lacking Rh antigens have
membrane abnormalities that shorten cell survival, although the severity varies among
affected individuals. Shortened red blood cell survival and variably altered activity of the
MNSsU and Ena antigens have been consistently observed, but the degrees of
hemolysis and anemia differ in different subjects. Since Rh antigenic activity appears to
reside on lipoprotein molecules integrally enmeshed in the red blood cell membrane, it
is not surprising that cells deficient in Rh activity have defective membrane function.