only a slight degree. In none of the cases was enlargement of the liver or spleen noted.
An additional case of HDN, apparently due
to anti-Jk’, has been reported by Kanner.8
This case differs radically from those men-tioned previously in that the infant was “very
jaundiced and anemic” and died at two days
of age. This case has not been included in
Table I because insufficient data precludes any but the most superficial type of comparison.
Despite the latter poorly documented case, there appears to be some basis for optimism in Jkb sensitizations. Prenatal screening for
irregular antibodies, which previously was, in
general, limited to a search for anti-Rh0, re-cently has been expanded in many institutions
to include testing for all of the more common
irregular antibodies. Such vigorous screening will undoubtedly disclose an increased number of Jk’ sensitizations. When this antibody is
discovered during the prenatal period, serial
titers would of course be of interest, but, in
the absence of strong indications to the con-trary, an optimistic and conservative approach would appear to be indicated.
Certain characteristics of the anti-Jk’
anti-body are suggested by the cumulative data of
Table I. In each of the cases, as well as that
of Kanner, antibody production apparently
was initiated at the time of pregnancy. A dos-age effect, i.e. , a difference in degree of
re-activity of the antibody with homozygous cells
(JkbJkb) and heterozygous cells (JkaJkb), was noted in three of the four cases including the
present one. The antibody, generally, was best
demonstrated by the ICT and the reaction
was not enhanced by the addition of
potenti-ating enzymes (bromelin, papain, etc.).
Con-trary to previous reports,1 the antibody
re-mained stable during prolonged storage in the
frozen state in at least three of the studies.
SUMMARY
This report concerns the fifth recorded case
of HDN due to anti-Jk’. Correlation of the
present data with that of previous studies
sug-gests that HDN resulting from Jk’
incom-patibility generally, although apparently not inevitably, follows a benign clinical course. A summary of some of the serologic characteris-tics of anti-Jk’ is also included.
VITA Z0DIN, MT. (ASCP) B.B.
ROBERT E. ANDERSON, M.D.
The Clinical Laboratories and the
Department of Pathology, Bernalillo
County-Indian Hospital and University of New Mexico Medical School
Albuquerque, New Mexico
REFERENCES
1. Race, R. R., and Sanger, Ruth: Blood Groups
in Man, 4th Ed. Oxford : Blackwell Scien-tific Publications, pp. 275-285, 1962.
2. Plaut, G., 1km, E. W., Mourant, A. E., Sanger,
R., and Race, R. R. : A new blood-group antibody, anti-Jk1’. Nature (London), 171:
431, 1953.
3. Sanger, R., Race, R. R., Rosenfleid, R. E., and
Vogel, P. : A serum containing anti-s and
anti-Jk”. Vox. Sang., 3:71, 1953.
4. Van Loghem, J. J., Heier, A. M., Van Den
Hart, M., and Sanchez, V. R. : A serum
con-taming anti-Jk”, anti-C and anti-M. Vox.
Sang., 3:115, 1953.
5. Rosenfield, R. E., Ley, A. B., Haber, G., and
Harris, J. P.: A further example of anti-Jk”.
Amer. J. Gun. Path., 24:1282, 1954. 6. Kornstad, L., and Halvorsen, K. : Haemolvtic
disease of the newborn caused by anti-Jk’. Vox. Sang., 3:94, 1958.
7. Geczy, A., and Leslie, M. : Second example of hemolytic disease of the newborn caused
by anti-Jk”. Transfusion, 1:125, 1961. 8. Kanner,
J.
: Anti-Jk’ in ervthrobiastosis fetalis.Amer. J. Obstet. Gynec., 83: 1253, 1962. 9. Wagman, E., and Bove, J.: Hemolvtic disease
of the newborn caused by antiJkb. Amer.
J. Clin. Path., 41:481, 1964.
10. Joseph, J., Awer, E., Laulight, M., and
Scud-den, J.: Delayed hemolytic tm-ansfusion re-action due to appearance of multiple anti-bodies following transfusion of apparently compatible blood. Transfusion, 4:367, 1964.
The
Effect
of
Repeated
Mumps
Skin
Tests
on
Skin
Sensitivity
to Mumps
Antigen*
The mumps skin test, developed by Enders
et al.,1 in 1945, has been especially useful in
identifying individuals who are immune to
mumps either as a result of clinical illness caused by the mumps virus or a subclinical infection. A positive skin test can be
demon-strated in 98% of persons who have a rise in
complement-fixing antibody titer to mumps
virus, and skin hypersensitivity may develop from 1 week to 3 months after infection.#{176}2
a“A skin test with mumps antigen is positive
when the diameter of the emythema with or
read 24-48 hours after an intradermal injection
of 0.1 cc of antigen into the flexor surface of the
forearm.”
EXPERIENCE
AND
REASON-BRIEFLY
RECORDED
423Although repeated skin tests with mumps
anti-gen are not commonly performed, occasionally
it is necessary to repeat a skin test within a
few months or a year after a previous one.
Under such circumstances there may be
diffi-(ulty in interpreting the result, as was the case
with
C.A.,
an 11-year-old Negro male, whowas seen with acute parotitis in May, 1963.
One day after the onset of parotid swelling a
mumps skin test was applied which was
re-1)Orted to be negative. Such a result would
have been expected even if the swelling had
l)een due to mumps virus because insufficient
time had elapsed for delayed hypersensitivity
to have developed to mumps antigen. The
child was next seen one year later, again with
acute parotitis. A mumps skin test was strongly
positive 3 days after the onset of parotid swell-ing. This again was too short an interval for
skin sensitivity to have resulted from the
cur-rent episode. No skin test control was used
with the antigen in either test. The diagnosis
of the second episode of parotitis depended
upon whether the child had experienced an
infection with mumps virus in 1963 or whether
the skin test applied at that time had
sen-sitized him sufficiently to have resulted in a
positive reaction to the second test a year
later.
Since none of the reported studies on the
use of the munips skin test was designed to
evaluate specifically the effect of repeated
skin testing on the size of the skin reaction
in the absence of the disease, the present
in-vestigation was undertaken.
STUDY POPULATION
Nineteen preschool children, ranging in age from 4 months to 5 years of age, were selected
for study from one of the outpatient clinics
of the Cleveland Metropolitan General
Hos-pital. Young children were recruited because
they would be less likely to have had
pre-vious experience with mumps virus. None of
these subjects had a history of previous
mumps, recent exposure to the disease, or
known allergy to eggs.
MATERIALS AND METHODS
The antigen and control materials were
sup-plied by Eli Lilly and Company. The antigen
was the commercially available killed virus
suspension prepared from extra embryonic
fluid of infected chick embryos (V-1059). The
control solution was identical to the test
ma-terial except for the absence of the mumps
antigen.
Each child received 0.1 cc of the test ma-terial intradermally on the flexor surface of
one forearm and 0. 1 cc of the control
ma-terial in the opposite forearm. Except for four
observations during the first skin test period, all tests were read by two observers 48 hours after administration of the test material. The
sites were examined and the diameter of the
erythema accurately measured in natural light.
The second observer did not know which arm
had been injected with the test material until
after the readings had been made. The
mea-surements made by the two observers were
averaged.
Each child received three skin tests. The
second test was given 1 month after the first
and, the third, 6% months after the second
test. At the time of each test the parent was
specifically questioned about any exposure to
mumps.
RESULTS
In no case did the two observers disagree
i)y more than 0.2 cm in the measurement of
the diameter of the reaction. The findings are
summarized in Table I.
No child displayed a positive reaction to
mumps skin test antigen during the first
two trials. There was one child (No. 7) who
had a positive reaction to the mumps antigen
at the time of the third trial. In this person,
the erythema which resulted from the
ad-mimiistration of control material after the second
trial exceeded 1.5 cm in diameter, while the
antigen at that time gave a reaction of 1.0
cm. After the third test, when a positive
re-action to the mumps antigen developed, the
erythema in the arm injected with the control
material was 0.2 cm. One week after the first
trial, this study child had played with a cousin
who had an illness diagnosed as mumps by a
physician. The study child never developed
any symptoms of disease.
The control material produced a reaction that was greater than that resulting from the antigen in 10 tests in eight subjects. Although
reactions to mumps antigen exceeded those
TABLE I
RESULTS OF SKIN TESTS IN STUDY CHILDREN
Child
‘%Tu,nber .-lge at is! I)ose
Erythema (cm)
-
----
-
---
--
- --- - ----Trial i Trio,! 2 Trial 3
T* Ct T C T C
I ‘2 3 4 .5 6 4 months 5 months 5 months 10 months 10 months 11 months 0.0 0.5 0.5 0.0 0.5 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.7 0.9 0.5 0.0 0.6 0.8 0.0 0.5. 0.5 0.2 0.0 0.8 0.0 0.8 0.0 0.2 0.0 0.5 0.0 0.0 0.0 (L() (1.0 0.0
7 l8months 0.5 0.5 1.0 1.5 3.2 0.2
8 9 10 11 12 13 14 15 16 17 18 19 l8months 20months 2years Syears Syears 3years 3years 4years 4 years 4years Syears 5years 0.5 0.5 0.2 0.5 0.0 0.5 0.5 0.3 0.6 0.0 1.1 0.5 0.0 0.0 0.0 0.2 0.5 0.0 0.0 0.0 0.2 0.0 0.5 0.0 0.6 0.3 0.6 0.2 0.6 1.0 0.5 0.3 0.6 1.1 0.9 0.0 0.0 0.2 0.5 0.2 0.4 1.0 0.0 0.0 0.0 0.5 1.0 0.7 0.5 0.5 0.2 0.2 0.0 0.0 0.0 0.0 0.5 0.0 0.2 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 (1.0 (1.0 0.0 0.0 0.5
* Reaction to test material.
f
Reaction to control material.instance was the diameter
greater than 1.1 cm.
of the reaction
It should be noted that there was
consider-able variation in the response of the same
individual at different times to both the anti-gen and the control material. The size of these
reactions was between 0.5 cm and 1.0 cm in
most instances.
COMMENT
Of 19 children given three trials with
mumps skin test antigen over a 73k-month
period, only one demonstrated a positive
mumps skin test. This child had a known
ex-posure to clinical mumps and may be
pre-sumed to have undergone mumps infection.
The reaction to the test antigen and
con-trol material was variable in the same
in-dividual at different times. Henle and her
associates have reported that when mumps
skin tests were applied repeatedly there was
variability of response on different occasions.’
This phenomenon has also been observed with
other skin test antigens.4 However, in only
one case was the erythema induced by the
control material great enough to constitute
a positive reaction. There was neither
evi-dence of sensitization to the egg protein per se, nor any systemic reaction.
The results of this study, therefore, indicate
that three intradermal injections of mumps
skin test antigen over a 73-month period will not result in the development of skin sensi-tivity in the absence of mumps infection.
SUSAN S. ARONSON,
M.D.
MARTHA
L.
LEPOW, M.D.Department of Pediatrics and Contagious
Diseases, Cleveland Metropolitan General
Hospital and the Department of Pediatrics Western Reserve University
School of Medicine
3,395 Scranton Road
Cleveland, Ohio, 44109
This investigation was supported in part by Public
Health Research Grant No. A105770-O1, from
the National Institute of Allergy and Infectious
EXPERIENCE AND REASON-BRIEFLY RECORDED 425
REFERENCES
1. i:idtrs, J. F., Cohen, S., and Kane, L. \V.:
Immunity in mumps. II. Development of
corn-)lement-fixing antibody and dermal
hyper-sensitivity in human beings following mumps.
J. Exp. Med., 81:119, 1945.
2 Enders, J. D., Kane, L. W., Mans, E. P., and
Stokes, J.:Immunity in mumps. V. Correlation
of presence of dermal hypersensitivity and
resistance to mumps. J. Exp. Med., 84:341,
1946.
3. Henle, C., Burgoon, J. S., Bashe, W. J., Jr.,
Burgoon, C. F., Stokes, J., Jr., and Henle, W.: Studies on the prevention of mumps. II. The effect of skin testing upon antibody level and
resistance. J. Immunol., 66:551, 1951.
4. Kuhns, \V. J.: Cellular and Hurnoral Aspects of
the Hypersensitive States. Ed. H. S.
Law-rence. New York: Paul B. Hoeber, 1959.
p. 541.
Eosinophilia
and
Agamma-globulinemia
While studying a group of children with the
visceral larva migrans syndrome’ we
en-countered in the patient group a child with
agammaglobulinemia. This child, in spite of an
almost complete absence of immune globulins,
exhibited the massive eosinophilia characteris-tic of the tissue phase of helminth infections.
CASE REPORT
L.C.S., a 16-month-old Puerto Rican boy, was
admitted to the University Hospital in San Juan on
February 19, 196:3, because of fever, wheezing and
cough of 3 weeks’ duration. His past history
re-vealed chronic diarrhea and episodes of purulent
conjunctivitis, otitis, and pneumonia. Pica had been noted for 5 months, and dogs, cats, pigs, and cows
were present near the child’s play area. The
pa-tient’s 6 siblings (3 boys) were said to be normal.
On physical exammation a purulent discharge
was noted in both ear canals. Wheezes and rales
were heard on auscultation of the chest and the
liver was palpated 3 cm below the right costal
margin. Blood counts and stool examinations are
recorded in the Table I. A urinalysis was normal.
Tine, Battey and histoplasniin skin tests were
nega-tive and gastric washings revealed no acid-fast bacilli. A chest x-ray revealed atelectasis of the right lower lobe. However, a follow-up film taken 1 month later showed re-expansion. A diagnosis of
the visceral larva migrans syndrome related to
massive Ascari.r infection ( and perhaps associated with other visceral parasites ) was made. The
diag-nosis of agamnmaglobulinemia was made 4 months
later when serum protein determinations were
carried out ( with the original specinmdn ol)taifled
on February 19, 1963
),
as part of the viscerallarva migrans studs’. The patient was found to
have no gamma-globulin band by serum
electro-phoresis.#{176} Other serum fractions were as follows:
albumin 3.7 gm/100 ml a, globulins 0.3 gm/100 ml
a, globulins 0.8 gm/100 ml and globulins 0.6
gm/100 ml. No gamma2 or gamma1 A globulin bands
were visible by imniunoelectrophoresis. A faint
gamma1 M globulin band was seen (see Fig. 1).
Quantitative immunogiobulin determinations
re-veaied a gamma globulin concentration of < 13 mg/100 ml and a gammas M globulin concentration of 1 1 mg/100 ml. Gamma1 A globulins were absent. His erythrocvtes were group 0 and isoagglutinins to group A, and B human erythrocytes were absent.
His serum contained no heterophile antibody and
noprecipitins to Ascari.s, Toxocara, or human blood group antigens. Heniaggiutination and flocculation
tests with Ascaris, Toxocara, and Dirofilarial
anti-gens were negative.t Antiglobulins ( found in half of the patients with the visceral larva nligrans
syndrome”tm ) were absent. The ganmnma2 globulin
concentrations in serum speciniens obtained on
4-6-6:3 and 1-30-65 were 23 mg/nil and 87 mg/mI
respectively. The second serum was obtained 44
(lays following a 200 cc blood transfusion (before
the institution of gamma-globulin treatment), and
the third serum was obtained 35 days following an
injection of gamma-globulin (12 cc).
Immunoeiectrophoretic patterns of the second
and third serum specimens revealed no detectable
gamma1 A or gamma, M globulin bands.
Treatmiient included blood tramlsfusions, antibio-tics and piperazine. After the diagnosis of agamma-giobulinemia was made he was started on monthly
gamma-globulin injections. On June 24, 1964,
be-cause of the persistence of pica and massive nurn-bers of Ascari.c ova in the stool he was started on monthly piperazine treatment. At his most recent clinic visit on February 12, 1965, he had been free of pica for 3 months and stool examination revealed only Trichuri.s ova.
COMMENT
One of the intriguing questions raised by the study of tissue helminth infections concerns the
etiology of the massive eosinophilia which
ex-ceeds that found in any other disease process.
Although one investigator has postulated that
the eosinophil plays ami early and essential role
ill antibody formation,’ others have suggested
for this cell a protective function. 4
and demonstrated the chemotactic
0
See Reference 1 for methods.1 The hemagglutination and flocculation tests with helminth antigens were carried out by Dr.
Irving Kagan, Communicable Disease Center,
