Clinical Science (1970) 39, 467473.
DEMOGRAPHY OF SERUM IMMUNOGLOBULINS:
D I F F E R E N C E S I N I g G A N D IgM LEVELS I N TWO
NORMAL MEXICAN ADULT POPULATIONS
D. ALARC6N-SEGOVIA
AND
EUGENIA FISHBEIN
Immunology Laboratory and Rheumatology Service
Instituto Nacional de la Nutricibn, Mexico City, Mexico
(Received 12 January 1970)
SUMMARY
1. The three major immunoglobulins were quantitatively determined in the serum
of 112 healthy Mexico City residents by the single radial immunodiffusion method.
2. Mean levels of IgG and particularly of IgM were unusually low as compared
to (a) mean levels reported from elsewhere, (b) a group of thirty-eight healthy residents
of Acapulco, Mexico of similar racial background and income and (c) a ‘British’
standard reference serum.
3. It is suggested that low IgG and IgM levels in Mexico City residents may be
related to its high altitude.
4. Diminished immunoglobulin levels, particularly those of IgM, might be a
compensatory mechanism for the increase in blood viscosity caused by high altitude
erythrocytosis.
Immunoglobulin levels in normal adults probably result from an interplay of genetic and
environmental factors (Rowe, Boyle & Buchanan, 1968a). The exact nature of these factors
and of the proportions in which they participate are unknown, but as a result of their role
there is great variation in the levels of immunoglobulins reported in studies of normal adults
from different locations despite generalized use of the single radial immunodiffusion method
for their quantitation (Fahey & McKelvey, 1965).
In this study, normal adults in Mexico City were found to have unusually low mean levels
of IgG and particularly of IgM. Another Mexican population was selected for study in order
to determine whether racial or environmental factors were responsible for such low levels.
This second group was from Acapulco (a sea level, tropical location where malaria has been
eradicated recently). Although most individuals in both groups were of mixed AmerindianCaucasian descent, IgG and IgM levels differed significantly between the Acapulco and the
Mexico City residents. Evaluation of factors which may account for differences in immunoCorrespondence: Dr D. Alarcbn-Segovia, Jnstituto Nacional de la Nutricibn, Calle Dr. Jim6nez No. 261,
MCxico 7, D.F.MCxico.
467
468
D . A lar cdn-Segovia and Eugenia Fishbein
globulin levels between groups from various locations, may bring some insight into the
environmental determinants of immunoglobulin levels in healthy adults.
MATERIAL AND METHODS
Subjects and locations
Group I consisted of 112 healthy Mexico City residents ranging from 16 to 78 years. Sixtynine were males and forty-three were females; thirty were blood bank donors and the rest
were hospital personnel and other volunteers. They came from different parts of the country
or were born in Mexico City itself. A few were immigrants but all members of this group had
resided in Mexico City for at least 2 years. The group is representative of the mixture of races
that constitute the Mexican population with various proportions of different Amerindian
groups and Caucasian, particularly Spanish. Low and middle income populations were
represented.
Mexico City has a temperate climate and is located at an altitude of 2240 m above sea level.
Group I1 consisted of thirty-eight normal adults or adolescents residing in or close to
Acapulco, Mexico. Their age ranged from 16 to 80 years. Twenty-two were males and sixteen
were females. The majority were born in the area but there were a few from other parts of
the country as well as immigrants. All of them had resided in the area for at least 2 years.
Low and middle income populations were represented. Racially, this group was similar to
group I except for some Negro admixture which can probably be traced back to African negro
slaves brought into the coasts of Mexico where they could stand heat and malaria better than
Indians. Negro features were detectable in seven subjects in this group.
Acapulco is on the Pacific coast of Mexico and has a tropical climate. Malaria was considered eradicated from the area a few years ago.
Serum immunoglobulins
Levels of immunoglobulins G, A, and M were determined by the method of Fahey & McKelvey (1965) using antibody-agar plates. These were initially prepared in our laboratory, but
having found commercially available Immunoplates suitable (Hyland Laboratories, Los
Angeles, California, U.S.A.), these were subsequently used without appreciable difference in
results. Sera were studied in large batches using sera from previous batches as well as known
standards in each batch as controls.
Diameters of precipitation rings were measured by means of a commercial illuminated
viewer (Hyland Laboratories) after 18 h diffusion for IgA and IgM, and 4 h for IgG; they
were then read from a standard curve obtained by plotting diameter against log concentration
of the standards. Sera with immunoglobulin concentrations higher than the standard were
re-tested at appropriate dilutions to fall between concentrations of the standards.
Standard reference serum
To allow comparison with results from other laboratories a ‘British’ reference serum
(W.H.O. 67/97) obtained from pooled sera from healthy British donors was used as a standard
(kindly provided by Dr D. S. Rowe, W.H.O. International Reference Centre for Immunoglobulins, Lausanne). Our results will thus be presented in mg of immunoglobulin per 100 ml
as well as in percentages of the concentration of immunoglobulin of such standard.
Demography of immunoglobulins
469
Statistics
Statistical analysis of our data and comparison with the studies of other authors where
enough data for such analysis were available, was done by determining the standard error of
the difference between means. Differences were considered statistically significant when the
difference between means was more than three times their SE (Bradford Hill, 1967).
RESULTS
The distribution of the immunoglobulin levels in the two Mexican populations is shown in
Fig. 1.
40r n
-:r
L
IgM
-
20
10 2c
39
‘
0
Group1
GroupII
I
I
I
I
I
I
I
60-79 1100-119 140-159 180-199r200
Concentration as % of standard
FIG.1. Distribution of immunoglobulin levels in two Mexican populations. Concentrations are
expressed as percentage of the ‘British’ standard reference serum (W.H.O. 67/97). Absolute
levels of this serum were: IS; 1140, IgA 180, IgM 93, mg/loO ml.
Immunoglobulin G
The mean level of IgG in Mexico City residents was 914 mg/100 ml with SD of 525. Individual values ranged between 400 and 2500 mg/100 ml.
Acapulco residents had more of a ‘normal’ distribution curve with mean values of 1456& 551
(SD) mg/100 ml. Individual values ranged between 700 and 2520 mg/100 ml. The observed
difference between the two means was 5.4 times its SE.
There was no sex difference in mean IgG values in Mexico City residents. Acapulco males
had a higher mean level of IgG than females. The difference was 2.3 times its SE (Table 1).
D. Alarcdn-Segovia and Eugenia Fishbein
470
TABLE
1. Mean levels of the three major immunoglobulins in residents of
Mexico City (Group I) and Acapulco (Group II) according to sex
IgG(mg/100 ml)
IgA(mg/100 ml)
IgM(mg/100 ml)
Group
Male
Female
Male
Female
Male
Female
I
98 1
915
223
244
48
42
I1
1643
1263
216
192
92
92
Immunoglobulin M
The mean level of IgM in Mexico City residents was 48527 (SD) mg/100 ml. Individual
values ranged from 16 to 150 mg/100 ml.
Acapulco residents had a mean level of IgM of 92522 (SD) mg/100 ml, ranging from 49 to
150 mg/100 ml. The difference between the means of the two groups was 11 times its SE.
There was no significant difference in the IgM concentration between sexes in either group
(Table 1).
Immunoglobulin A
There was no significant difference between mean IgA levels in the two groups (group I :223 &
108 (SD)mg/100 ml, range 70-450; group 11: 209+63 (SD) mg/100 ml, range 108-450).
The difference between the means was equal to the SE. There was no significant sex difference
in IgA concentration in either group. Mexico City females had a higher mean level of IgA
than those from Acapulco. The difference between the means was 3-8 times the SE (Table 1).
DISCUSSION
Genetic factors other than race are significant determinants of all three major classes of
immunoglobulins in the healthy child. In the adult such factors continue to predominate in
determining IgG levels, but environmental factors become more important in determining
IgA and IgM (Rowe et al., 1968a). Race seems to influence primarily IgG (Turner & Voller,
1966; Lichtman, Vaughan & Hames, 1967; Rowe, McGregor, Smith, Hall &Williams, 1968b)
and IgM (Turner & Voller, 1966; Wells, 1968) levels. Thus Negroes have higher IgG (Turner
& Voller, 1966; Lichtman, et al., 1967; Rowe et al., 1968b) and somewhat higher IgM
(Turner & Voller, 1966; Lichtman et al., 1967) levels than have Caucasians. Both immunoglobulins are distributed over a wider range in the Negro. In New Guinea, Watut aborigines
have higher IgG and IgM levels than non-Watut aborigines and both have higher levels than
Caucasians (Wells, 1968).
Sex seems also important in the determination of IgM levels in some populations (Lichtman
et al., 1967; Butterworth, McClellan & Allansmith, 1967; Rowe et al., 1968b) but not in
others (Rowe et al., 1968b), where apparently, other factors predominate. No significant
difference was detected between rural and urban populations in one study (Lichtman et al.,
1967).
Levels of the three major immunoglobulins remain stable in healthy adults over extended
periods of time (West, Hong & Holland, 1962; Allansmith, McClellan & Butterworth, 1967).
Although the various studies included in Table 2 were done using the same method for
Gambia
Netherlands
Rowe et al. (1968)
Stoop et al. (1969)
AlarobnSegovia &
FiShbein
(Thisstudy)
NewGuinea
Wells (1%8)
1200
1020
91
30
112
38
white
White
Mexiw
Group I (Mexico City) Mixed
GroupII Acapulco Mixed
~~~~~
5.4
0
- 209+63
(108450)
-0 48+27
92+22
100
190
223+108 (70-450)
89
238
1-3 2.0 92+37
123
89
(16-150)
(49-150)
(68515)
(38-220)
(31-227)
(35-210)
1.9 2.7 74+33
5.5 4-3 120i58.9
4 0 2.8 133+68-4
(47-147)
0 99+27
1.4
110
270
(86-300)
(68-564)
(52-268)
II Mean+SD(range)
3.9 3-8 123+35
1
D~erence+
group
IgM(mg/loOml)
+
= Differenceof the mean with that of each of the two groups (I
& II) in this study expressed as number of times their SE.
Significant = >3.0.
914+525 (400-2500)
1456k551 (700-2520)
(1370-2640)
- 5-4
1919
12
146
215
1549
30
NonWatut
AbOrigiwS
Watut
Aborigines
(870-2560)
130
white
4 6 2.0 250+105
1250* 300
1023
(515-1560)
white
35
24
169
2.1 3.7 157+80
5.3 0 175+79-2
(105-358)
Belgium
(1013-1092)
vcys & claesem (1968)
1045
Not stated
U.S.
AUansmith et ul. (1%7)
315
white
Negro
U.S.
Lichtman et al. (1967)
1112+320
1408*346
(135450)
1647+24O (1197-2222) 11.6 1.9 258+95
36
Mixed
Venezuela
Arends&Gallango(1966)
112
108
(61-330)
3.3 2.8 uK)+61
1158+305(569-1919)
30
Not stated
US.
160
Stiehm & Fudenberg (1966)
loo0
24
Not stated
U.S.
4.7 2.1 280+70
1240+220
20
Tomasi (1965)
Not stated
II Mean+SD(range)
I
MeanfSD(range)
Number
Race ofsubjects
US.
Country
Dif€eltllCC+
group
IgA(mg/lOOml)
Fahcy & McKelvey (1965)
Authors
IgG(mg/100ml)
TABU2. Serum levels of the three major immunoglobulins in various populations
11
5
(D
0
- 11.0
11.0
7-3
P
2
3
.
I
.
e%
10.2 5.6 @
12.1 6-7
4.4 3.0
10.2 1.2
9.3 3.8
I
Difference+
group
472
D . Alarcdn-Segovia and Eugenia Fishbein
the determination of immunoglobulin concentrations, there is considerable variation in their
results. Immunoglobulin levels found in various laboratories could be more readily correlated
by referring to a given standard such as the ‘British’ reference serum used in this study.
Mean levels of IgG and particularly of IgM were found to be lower in healthy Mexico City
residents than in any of the healthy adult populations drawn from and reported on elsewhere
(Table 2). Mean IgM and IgG were also lower in residents from Mexico City than in those
from Acapulco. The majority of sera in group I had concentrations of IgG and IgM below
those of the ‘British’ reference serum (Fig. 1). The only ethnic variation between our groups
consisted of some Negro admixture in the Acapulco residents. Although race might account
for the higher mean IgG levels in Acapulco residents than in Caucasians, as reported elsewhere, it is unlikely that the difference with the Mexico City residents can be accounted for
on this basis. Furthermore, immunoglobulins in the seven Acapulco residents that had Negro
features did not differ significantly from those in the rest of the group (mean IgG: 1263 mg/
100 ml; IgM: 104 mg/100 ml).
Another study of immunoglobulins in a Latin American population has been done in
Venezuela (Arends & Gallango, 1966). Because of Negro admixture, the population studied
by these authors probably resembles more that of our group 11. The mean levels of the three
immunoglobulins were similar to those in group I1 except for a slightly lower mean IgM in the
Venezuela group (Table 2).
Although malaria was endemic in the Acapulco area until a few years ago, it has now
practically been eradicated. It is therefore unlikely that the higher IgM levels in the Acapulco
than in Mexico City residents (where there is no malaria), could be due to previous malaria
since increased IgG and IgM levels in malaria infection seem to depend on the presence of
parasitaemia (McFarlane & Voller, 1966; Tobie, Abele, Wolff, Contacos & Evans 1966).
Although intestinal parasites are common in the Acapulco area, other blood parasitic infections are not particularly prevalent.
The main difference between both locations in our study, as well as between Mexico City
and those studies reported from elsewhere, seems to be the altitude. Low IgG and particularly
low IgM levels in Mexico City residents could be related to the high altitude of this location.
Trapani (1969) has found that mice kept at high altitude have a smaller number of antibodyforming cells in their spleens following antigenic stimulation. It is particularly interesting
that he found a marked reduction in circulating 2-mercaptoethanol sensitive (19s) antibody as
compared with animals similarly studied but at lower altitudes. One possible explanation for
diminished immunoglobulin production and resulting low IgM levels at high altitude may be
that it is part of a compensatory mechanism to avoid excessive blood viscosity (Fahey, Barth &
Solomon, 1965) when erythrocytosis tends to occur because of high altitude.
ACK NO WLEDGMEN T
This work was supported in part by a grant from Laboratorios Clfnicos de Mtxico.
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