d. A third type of defective Rh gene expression is found in patients of the Rhmod
phenotype, which seems to arise from the homozygous occurrence of another recessive
"suppressor" gene. These patients have congenital hemolytic anemia and much
reduced, but not completely absent, Rh activity. Rhnull cells consistently lack the LW
antigen despite the fact that the individual has normal LW genes; Rhmod cells do have
e. Most Rhnull individuals came to medical attention because their serum
contained antibodies, but this is not universal. Transfusion seems to be highly
sensitizing, but not all parous Rhnull women have developed pregnancy-related
antibodies, and one never-transfused man developed antibody without known
stimulation. Although all are within the Rh system, the antibodies have a spectrum of
reactivity, from identifiable anti-e and anti-C to the serum called anti-Rh29, which reacts
with all cells tested except other Rhnull cells.
2-24. Rh ANTIBODIES
a. With the exception of occasional examples of anti-rh"(E) and anti-Cw
occurring without known stimulus, most Rh antibodies result from immunization by
pregnancy or transfusion. Rho(D) is far and away the most potent antigen, followed by
hr'(c) and rh"(E). Although strong reactions may be seen in saline agglutinating
systems, most Rh antibodies react best by enzyme or anti-globulin techniques. Even
serums with strong saline-active anti-Rho(D) usually react at far higher dilutions in anti-
globulin tests. Some workers find enzyme techniques especially useful for detecting
weak or developing Rh antibodies. Sensitization tends to persist for many years, and
even if circulating antibody is no longer detectable, subsequent antigenic exposure
produces rapid secondary response.
b. Anti-Rho(D) usually reacts in an all-or-nothing fashion, without distinguishing
between red blood cells from homozygous and heterozygous individuals. Dosage effect
can often be demonstrated in antibodies against rh"(E), hr'(c) and hr"(e), while anti-
rh'(C) sometimes behaves this way. Detecting antigen strength by tube-testing with
agglutinating antibodies provides data that are quantitatively poor. Accurate
quantitation of antigenic sites requires methods such as radioisotope labeling,
immunoferritin localization, or automated procedures.
c. Virtually all the Rh antigens have been discovered because of human
antibodies. The complexity of the Rh system testifies to the diversity of Rh antigen
activity and to the remarkable discriminatory capacity of the human immune response.
It is not known why some antigens evoke antibodies after a given antigenic challenge
while others do not.