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Serum IgD concentration in pregnant women
CLINICAL
IMMUNOLOGY
Serum
AND
4, 9-15 (1975)
IMMUNOPATHOLOGY
IgD Concentration
in Pregnant
Women
ROBERTO R. KRETSCHMER,H~CTORG~MEZ-ESTRADA, JULIO C. MARGAIN, JORGEARELLANO,RODOLFO RAMOS,AND PORFIRIO LANDAZURI Sections of Immunology and Biostatistics, Departamento and Hospital de Gineco-Obstetricia II. Centro MPdico
de lnvestigacidn National, I.M.S.S..
Cientijica MPxico
Received June 10. 1974 IgD levels were determined in maternal sera (obtained at delivery) at different stages of gestation, and found to be low in premature deliveries but normal in term deliveries when compared to those of normal nonpregnant women. Maternal IgD levels at delivery revealed a significant exponential correlation with duration of pregnancy. These results are at variance with the results of other surveys. The discrepancy could be explained on ethnic or methodological grounds. No correlation was found between maternal IgD levels and the degree of HL-A disparity between mother and product. Specificities HL-A-2 and HL-A- 13 in the mother revealed a discrete correlation with IgD levels at delivery.
Immunoglobulin D (IgD) was recognized as a distinctive class of immunoglobulin in 1965 (1,2) and since then a few antibody activities related to this class have been documented (3-7). Little is known, however, concerning the biological function of these molecules (8,9). IgD constitutes about 0.2% of all serum immunoglobulins, its concentration ranging from nondetectable levels to 30 mg/lOO ml (mean = 3 mgll00 ml with no differences between sexes) (10-l 2). On the other hand, the number of surface IgD-bearing lymphocytes has been shown to be as high as 2.7% which represents approximately 18% of all lymphocytes bearing surface immunoglubulins (9,13). One area of particular biological interest has been the relation of IgD to pregnancy. Elevated levels of IgD in maternal sera at term have been reported by several authors, although the role played by labor and delivery has not been clarified (10,14,15). Moreover, 1gD does not cross the placenta and only 4.5% of normal cord sera contain measurable amounts of IgD, presumably of fetal origin (16). Contrasting with this virtual absence of IgD in cord sera, is the high number of surface IgD-bearing lymphocytes in cord blood (15% vs 2.7% in normal adult blood), the majority of which also carry simultaneously IgM on their surface (17). The purpose of the present study was to measure serum IgD levels in mothers at delivery with normal pregnancies and deliveries at different gestation stages. Possible correlations were sought with the degree of genetic (HL-A) disparity between mother and product, number of previous pregnancies, weight of the product, age of the mother. and ABO/Rh blood-group discrepancies between mother and product. MATERIALS
AND METHODS
Patients. Blood samples were obtained at the time of delivery (within 5 min of expulsion) from 72 healthy pregnant Mexican women of low socioeconomic status undergoing labor at different stages of gestation. Umbilical-cord blood 9 Copyright All rtght\
6 1975 by Academic Press, Inc. of reproduction in any form reserved.
10
KRETSCHMER
ET
AI.
samples were obtained simultaneously. Control subjects were 85 healthy adult women who were neither pregnant nor taking contraceptives ( 14). IgD determinations. IgD was quantitated simultaneously in all serum samples (longest storage at -50°C = 3 mo) by single radial immunodiffusion using commercially available IgD plates (Behringwerke) (18). The monospecificity of the goat anti-human IgD antisera used in the plates was assessed by immunoelectrophoresis (19). Pure standard reference sera contained 1.27 mg/ 100 ml, 2.54 mg/lOO ml, 5.8 mg/lOO ml, and 12.0 mg/lOO ml IgD, respectively. All tests were done by blind duplicate with excellent reproducibility. ABO-Rh typing. Blood samples were typed following standard methods as described by Dunsford and Bowley (20). Lymphocyte preparation and typing. Leukocyte-antigen typing was performed in 34 paired maternal and fetal blood samples of term deliveries. Lymphocyte5 were obtained using Ficoll-Hypaque density-gradient centrifugation (3 1). Typing was done in triplicate by the microcytotoxicity test of Terasaki (22). Throughout this study 16, mostly monospecific, iso-antisera against 13 known HL-A specific antigens were used: first locus (HL-A 1,2,3,9.10,1 1). second locus (HI,-A .5,7,8,12,13), 4a and 4b. Six degrees of HL-A disparity between mother and fetus were established in accordance with the recommendations of the 1970 Histocompatibility Testing Workshop (23). Duration of pregnancy. This was assessed by using the mothers recollection of the date of onset of her last menstrual period which according to Treolar (24) is sufficiently free of error to make any effect neglible when gestational intervals are expressed in weeks. Of the 72 cases included in this study, 50 were considered term deliveries (38-42 wk of gestation) and 32 premature (25-37 wk of gestation). STATISTICAL
ANALYSIS
Serum IgD concentrations were initially analyzed by Henri’s test (25). Since the distribution of values did not follow a Laplace-Gauss model. all data were subjected to square root (X = m) and logarithmic transformations. Bartlett’s test (26), however. did not reveal them to be homoscedastic, forestalling a one-way analysis of variance and Scheffe’s (27) method of multiple comparisons. as done in other studies (10). Therefore, a nonparametric one-way analysis of variance by ranks (Kruskal-Wallis test) (28), and a Mann-Whitney U test (28) of all possible combinations were used. Furthermore. serum IgD concentrations were analyzed following eight different statistical models (29) (lineal, quadratic. exponential, logarithmic, potential, geometric, reciprocal-lineal. and constant) by the least square roots method to find possible correlations with various events (gestational age at delivery, weight of product, parity, maternal age, and HI.-A discrepancy). Data were processed by an IBM-I 130 (Forthram IV) computer. and the best fit chosen by residual-comparison analysis. error and F-ratio of variance analysis of each of the models used. Ail cases ] 72 ] were included for correlation with gestational age (and concomitantly with birth weight of the product), whereas only term cases [.50] were considered for correlation with the other parameters (including birth weight). Finally, associations between individ-
IgD
THE
EFFECT
OF GESTATIONAL
IN
11
PREGNANCY
TABLE 1 TIME ON MATERNAL
IgD
LEVELS
Number of specimens 1 Controls 2 Term deliveries (38-42 wk) 3 Premature deliveries (25-37 1 vs 2 P > 0.05 I or 2 vs 3 P < 0.05
Mean
85 50 22
wk)
AT DELIVERY
IgD (mg/lOO
ml) % SD
3.09 + 2.24 2.99 + 1.83 1.97 i 1.35
ual HL-A specificities (maternal and fetal) and serum IgD levels were analyzed by the method of difference in proportion by normal approximation (25). RESULTS
The concentration of IgD in the three groups of women that were studied are listed in Table 1. The Mann-Whitney U test revealed no difference between the mean IgD concentration in maternal term sera and control sera, whereas the sera of women with premature deliveries had a significantly lower mean concentration when compared to the other two groups (P < 0.05). The Kruskal-Wallis
b FIG. 1. Distribution of IgD term deliveries, and premature
i
concentration deliveries.
6 in sera from
PREMATURE
n=22
i
IgD
control
i
mg%
(nonpregnant)
women,
women
with
I2
KRETSCHMER
ET
Al
analysis. on the other hand, disclosed no significant difference of the mean IgD concentration in the three groups (P > 0.05). Individual values in these three groups followed a trimodal pattern of distribution (Fig. 1I. Correlations Gestational uge arrd +tleight c?fproduct. A highly significant exponential correlation was found between maternal IgD levels and gestational age (Y = 10.8 I. P < 0.001) (Fig. 2). Since as expected, birth weight of the product also correlated exponentially with the duration of pregnancy (P < O.OOS), a similar correlation was detected between maternal IgD levels and weight of their products (r = +0.63, P < 0.00 1). Yet, there was no correlation between maternal IgD concentration and birth weight of the product when only term deliveries were considered (u = +0.40, P > 0.05). Parity. Parity ranged from 1 to I.5 with propositi in all groups. ‘There was no correlation between concentration of IgD in maternal term sera and parity. Maternal age. Maternal age ranged from I6 to 42 yr (mean 26.6 yr) in this study. A discrete correlation was found between IgD concentration in term sera and maternal age using a quadratic model (r = +0.53. P < 0.051, while there was no correlation between IgD concentration and age in the control group.
LXeOlONL
MODEL I
6.0 1 -I
= 72 r = odl (+I p
+ =cAl.cuLATLD x 5.03 _ E n ii E c
l
=oeSEnvE0
(lIEAll)
I t
4.0/
-
I
l
/+
E
z m E 0
/+
3.0-
0
-_
.
2.0-
,:’
+/+
.
”
.
ty +I+
l.O-
2’
l
.
;_
/+
l /+
/. l At
.
+’ .
I
25
I
26
I
I
I
I
I
27
26
29
30
31
I
32
11
33
I1
34
35
11
36
37
I
36
39
I
I
40
4l
I
42
~ESTATIOWAL FIG. 2. Exponential correlation between arithmetic mean of observed values for least square roots method.
maternal IgD each gestational
levels week
I
‘
43
44 16E
and gestational age at delivery. is plotted. Calculated values
(we.tv) by
The the
IgD
IN
PREGNANCY
13
HL-A discrepancy. There was no correlation between concentration of IgD in maternal term sera and the six conventionally chosen degrees of HL-A disparity between mother and fetus. ABO and Rh Incompatibility Six instances of ABO and one of Rh (D) incompatibility (this coinciding with an A/O incompatibility) were detected among the 50 term deliveries. Maternal IgD levels in these six cases were among the highest in the study (6.0, 5.6, 5.6, 5.2, 2.4, and 0.64 mg/lOO ml), with a mean IgD of 4.26 mg/lOO ml. The lowest IgD concentration in this group was that of the maternal-fetal pair with double (AO/RhD) incompatibility. Statistical analysis of these results by means of the Mann-Whitney U test, however, did not reveal them to be significant when compared to the remnant 44 term deliveries (mean IgD concentration 2.82 mg/lOO ml). HL-A Specijicities The association of HL-A specificities and IgD concentration in maternal term sera was studied by distributing the latter in four groups ( + 2 SD, + 1 SD, - 1 SD, and - 2 SD) and establishing the independent incidence of maternal and fetal HL-A specificities in each group. Also, sets of HL-A specificities present in the mother and absent in the fetus, or vice versa (HL-A discrepancy sets), were identified and their incidence established in each of said four groups of IgD concentration in maternal serum at term. Using the former approach it was found that maternal HL-A-2 was discretely associated with IgD levels above the mean (P < 0.05) whereas maternal HL-A-13 had a slightly stronger association with IgD levels below the mean (P < 0.01). No fetal HL-A specificity seemed to associate significantly with any maternal IgD level. Furthermore, no set of HL-A discrepancy was associated with any of the four IgD levels chosen for this analysis. DISCUSSION
Our data on IgD concentration in adult nonpregnant women are similar to that of other publications (lo-12,14,15,30,3 l), and the trimodal distribution of individual values in all groups clearly confirmed Rowe’s original observation (2). On the other hand, the lower levels of maternal IgD in premature deliveries and the normal levels of IgD at term are at variance with other studies, where an elevation of IgD in late pregnancies-and normal levels in early pregnancies- has been consistently found (10,14,15). The reason for this discrepancy is not clear but differences in the time of obtention of the blood samples (pre- and postexpulsion) could be of critical importance (10,32). Furthermore, our survey was performed with Mexican-mestizo women of low socioeconomic status, whereas reports in the literature concern either Anglo-Saxon (14,15) or Negro patients ( lo), so that the discordant results could also be explained by an ethnic difference in the control of IgD concentration during pregnancy. Germane to this is Colwel’s observation that Vietnamese and Montagnard patients with malaria had distinctly elevated levels of IgD, while these remained normal in Cambodian patients (33).
14
KRETSCHMER
ET
AL..
In spite of these discrepancies, pregnancy was not without effect to maternal IgD concentration, even in our survey, as revealed by the highly significant exponential correlation between gestational age and maternal 1gD levels. Since weight of the product did not correlate with maternal IgD concentration in term deliveries, other phenomena associated with the cumulative effect of a growing conceptus are likely to be relevant to the peculiar behavior of 1gD during pregnancy ( 10,14). It has been proposed that elevated IgD levels in maternal sera at term represent antibodies directed either against leukocyte or trophoblastic antigens (14), and a factor can frequently be found in plasma of pregnant women which is capable of inhibiting mixed leukocyte cultures (34.35). A very attractive possibility is that this factor could belong to the IgD class. Our study, however,. did not disclose any significant correlation between maternal IgD levels at term and HL-A or blood-group maternal-fetal disparities. Since the survey waq limited to only a few antigenic specificities, further studies seem warranted to define the possible influence on maternal IgD levels of antigenic stimulation of the mother by the fetus. On the other hand. certain specificities in the mother (HL-A-2 and HL-A- 13) seemed to influence maternal IgD levels irrespective of their presence in the fetus. Again the limited character of this study precludes the assumption that these allotypes are. in fact, associated with the control 01 serum concentration of IgD, but the observation deserves further study. Finally. there was no correlation between IgD levels and parity in our survey. as opposed to Leslie’s observation (10) that women who had multiple pregnancies have more IgD than those who have not been previously pregnant. Again. an ethnic factor could account for these discordant results. The discrete correlation of maternal IgD levels and age in term deliveries contrasts with the lack of correlation between IgD levels and age in controls. Although the biological significance of this observation is obscure, it is not the first instance where an age dependency of IgD levels has been found (3). ACKNOWLEDGMENT We thank
Mr.
Rafael
Ronces
for his excellent
assistance
in the statistical
evaluation
of the result\
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. IO. Il. 12. 13. 14. 15.
Rowe, D. S.. and Fahey. J. L., J. &/I. Med. 121, 17 1. 1965. Rowe. D. S., and Fahey. J. L.. J. Exp. Med. 121. 185. 1965. Levine. B., and Redmond. A., Inr. Auc.11. AI/er~~ 21, 594. 1967 Ritchie. R. F., Arttzrifis Rtzeum. 11, 506. 1968. Heiner. D. C.. Saha. A., and Rose, B.. Fed. Proc~. 28. 766. 1969. Kantor, G. L.. Van Herle. A. J., and Barnett, E. V.. Cl& E.rp. fmmunol. 6, 95 1, 1970. Devey, M., Carter. D., Sanderson. C. J., and Coombs, R. R. A., Lanwf 2, 1280, 1970. Gleich, G. J.. Bieger, R. C.. and Stankievic, R., S~Yence 165, 606, 1969. Boxel, J. A., Paul, W. E.. Terry, W. D.. and Green, I.. J. Immunol. 109, 648. 1972. Leslie, G. A., Proc. Sot. Exp. Bio[. Med. 144, 741, 1973. Rogentine, G. N., Rowe, D. S.. Bradley, J.. Waldmann. T A., and Fahey. J. I~.. J. (‘tin. 45, 1467, 1966. Rowe, D. S.. Grabbe, P. A.. and Turner, M. W.. C’lin. 6.rp fmmunui. 3, 477. 1968, Aisenberg, A. C., and Bloch, K. J., N. Engl. J. Mad. 287, 271, 1972. Klapper, D. G., and Mendenhall, H. W.. .I. Immunof. 107, 9 I?, 197 I Gudson. J. P.. and Pritchard, D.. Gynrcol. Obster. J 12, 867. 1972.
tu,wr
IgD 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.
16. 27. 28. 29. 30. 3 I. 32. 33. 34. 35. 36.
IN
PREGNANCY
15
Leslie, G. A., and Swate, T. E., J. Immunol. 109, 47, 1972. Rowe, D. S., Hug, K., Forni. L., and Pernis. B., J. Exp. Med. 138, 965, 1973. Fahey, J. L.. and Lawrence, M. E.. J. Immunol. 91, 597, 1963. Scheidegger, J. J.. Int. Arch. Allergy 7, 103, 1955. Dunsford. I., and Bowley. C. Ch., “Techniques in Blood Grouping,” Vol. I. Oliver & Boyd. Edinburgh-London, 1967. Harris, R.. and Ukaejiofo. E. O., Lancet 2, 377, 1969. Terasaki, P. I., and McClelland, J. D.. Nature 204, 998, 1964. Terasaki, P. 1.. “Histocompatibility Testing.” Munksgaard. Copenhagen, 1970. Treolar, A. E., Behn, B. G., and Cowan, D. W.. Amer. .I. Obstet. Gynecol. 99, 34, 1967. Gremy. F., and Salmon, D.. “Bases Statistiques pour la Recherche Medicale et Biologique,” Dunod, Paris, 1969. Snedecor, G. W.. and Cochran, W. G., “Statistical Methods.” Iowa Univ. Press, 1967. Guenther, W. C., “Concepts of Statistical Inference.” McGraw-Hill, New York, 1965. Siegel, S., “Non-parametric Statistics for the Behavioral Sciences.” Int. Student Edition. McGraw-Hill, New York, 1956. in Regression and Related Topics. Metheun’s Monographs on Applied Sprent. P., “Models Probability and Statistics.” Metheun & Co.. London, 1969. Rundle, A. T., Clothier, B.. and Sundell, B.. Clirz. Chim. Actrr 35, 389, 1971. Sinsinha, S., Charaputana, Ch.. and Teera. R., Proc. Sot. Exp. Bid. Med. 140, 1062, 1972. Gusdon. J. P., Amer. J. Obstet. Gynecol. 103, 895. 1969. Colwell, E. J., Bernier, G. M.. and Earl. H. F., Trans. Roy. Sot. Trap. Med. Hyg. 65, 310, 1971. Ceppelini. R., Progr. Immunol. 1, 973, 1971. Kasakura, S., “Proc. 6th. Leukocyte Culture Conference” (M. R. Schwarz, Ed.), Academic Press, New York, 1972. Buckley. C. E., and Trayer. H. R., Clin. Exp. Immunol. 10, 257. 1972.
IMMUNOLOGY
Serum
AND
4, 9-15 (1975)
IMMUNOPATHOLOGY
IgD Concentration
in Pregnant
Women
ROBERTO R. KRETSCHMER,H~CTORG~MEZ-ESTRADA, JULIO C. MARGAIN, JORGEARELLANO,RODOLFO RAMOS,AND PORFIRIO LANDAZURI Sections of Immunology and Biostatistics, Departamento and Hospital de Gineco-Obstetricia II. Centro MPdico
de lnvestigacidn National, I.M.S.S..
Cientijica MPxico
Received June 10. 1974 IgD levels were determined in maternal sera (obtained at delivery) at different stages of gestation, and found to be low in premature deliveries but normal in term deliveries when compared to those of normal nonpregnant women. Maternal IgD levels at delivery revealed a significant exponential correlation with duration of pregnancy. These results are at variance with the results of other surveys. The discrepancy could be explained on ethnic or methodological grounds. No correlation was found between maternal IgD levels and the degree of HL-A disparity between mother and product. Specificities HL-A-2 and HL-A- 13 in the mother revealed a discrete correlation with IgD levels at delivery.
Immunoglobulin D (IgD) was recognized as a distinctive class of immunoglobulin in 1965 (1,2) and since then a few antibody activities related to this class have been documented (3-7). Little is known, however, concerning the biological function of these molecules (8,9). IgD constitutes about 0.2% of all serum immunoglobulins, its concentration ranging from nondetectable levels to 30 mg/lOO ml (mean = 3 mgll00 ml with no differences between sexes) (10-l 2). On the other hand, the number of surface IgD-bearing lymphocytes has been shown to be as high as 2.7% which represents approximately 18% of all lymphocytes bearing surface immunoglubulins (9,13). One area of particular biological interest has been the relation of IgD to pregnancy. Elevated levels of IgD in maternal sera at term have been reported by several authors, although the role played by labor and delivery has not been clarified (10,14,15). Moreover, 1gD does not cross the placenta and only 4.5% of normal cord sera contain measurable amounts of IgD, presumably of fetal origin (16). Contrasting with this virtual absence of IgD in cord sera, is the high number of surface IgD-bearing lymphocytes in cord blood (15% vs 2.7% in normal adult blood), the majority of which also carry simultaneously IgM on their surface (17). The purpose of the present study was to measure serum IgD levels in mothers at delivery with normal pregnancies and deliveries at different gestation stages. Possible correlations were sought with the degree of genetic (HL-A) disparity between mother and product, number of previous pregnancies, weight of the product, age of the mother. and ABO/Rh blood-group discrepancies between mother and product. MATERIALS
AND METHODS
Patients. Blood samples were obtained at the time of delivery (within 5 min of expulsion) from 72 healthy pregnant Mexican women of low socioeconomic status undergoing labor at different stages of gestation. Umbilical-cord blood 9 Copyright All rtght\
6 1975 by Academic Press, Inc. of reproduction in any form reserved.
10
KRETSCHMER
ET
AI.
samples were obtained simultaneously. Control subjects were 85 healthy adult women who were neither pregnant nor taking contraceptives ( 14). IgD determinations. IgD was quantitated simultaneously in all serum samples (longest storage at -50°C = 3 mo) by single radial immunodiffusion using commercially available IgD plates (Behringwerke) (18). The monospecificity of the goat anti-human IgD antisera used in the plates was assessed by immunoelectrophoresis (19). Pure standard reference sera contained 1.27 mg/ 100 ml, 2.54 mg/lOO ml, 5.8 mg/lOO ml, and 12.0 mg/lOO ml IgD, respectively. All tests were done by blind duplicate with excellent reproducibility. ABO-Rh typing. Blood samples were typed following standard methods as described by Dunsford and Bowley (20). Lymphocyte preparation and typing. Leukocyte-antigen typing was performed in 34 paired maternal and fetal blood samples of term deliveries. Lymphocyte5 were obtained using Ficoll-Hypaque density-gradient centrifugation (3 1). Typing was done in triplicate by the microcytotoxicity test of Terasaki (22). Throughout this study 16, mostly monospecific, iso-antisera against 13 known HL-A specific antigens were used: first locus (HL-A 1,2,3,9.10,1 1). second locus (HI,-A .5,7,8,12,13), 4a and 4b. Six degrees of HL-A disparity between mother and fetus were established in accordance with the recommendations of the 1970 Histocompatibility Testing Workshop (23). Duration of pregnancy. This was assessed by using the mothers recollection of the date of onset of her last menstrual period which according to Treolar (24) is sufficiently free of error to make any effect neglible when gestational intervals are expressed in weeks. Of the 72 cases included in this study, 50 were considered term deliveries (38-42 wk of gestation) and 32 premature (25-37 wk of gestation). STATISTICAL
ANALYSIS
Serum IgD concentrations were initially analyzed by Henri’s test (25). Since the distribution of values did not follow a Laplace-Gauss model. all data were subjected to square root (X = m) and logarithmic transformations. Bartlett’s test (26), however. did not reveal them to be homoscedastic, forestalling a one-way analysis of variance and Scheffe’s (27) method of multiple comparisons. as done in other studies (10). Therefore, a nonparametric one-way analysis of variance by ranks (Kruskal-Wallis test) (28), and a Mann-Whitney U test (28) of all possible combinations were used. Furthermore. serum IgD concentrations were analyzed following eight different statistical models (29) (lineal, quadratic. exponential, logarithmic, potential, geometric, reciprocal-lineal. and constant) by the least square roots method to find possible correlations with various events (gestational age at delivery, weight of product, parity, maternal age, and HI.-A discrepancy). Data were processed by an IBM-I 130 (Forthram IV) computer. and the best fit chosen by residual-comparison analysis. error and F-ratio of variance analysis of each of the models used. Ail cases ] 72 ] were included for correlation with gestational age (and concomitantly with birth weight of the product), whereas only term cases [.50] were considered for correlation with the other parameters (including birth weight). Finally, associations between individ-
IgD
THE
EFFECT
OF GESTATIONAL
IN
11
PREGNANCY
TABLE 1 TIME ON MATERNAL
IgD
LEVELS
Number of specimens 1 Controls 2 Term deliveries (38-42 wk) 3 Premature deliveries (25-37 1 vs 2 P > 0.05 I or 2 vs 3 P < 0.05
Mean
85 50 22
wk)
AT DELIVERY
IgD (mg/lOO
ml) % SD
3.09 + 2.24 2.99 + 1.83 1.97 i 1.35
ual HL-A specificities (maternal and fetal) and serum IgD levels were analyzed by the method of difference in proportion by normal approximation (25). RESULTS
The concentration of IgD in the three groups of women that were studied are listed in Table 1. The Mann-Whitney U test revealed no difference between the mean IgD concentration in maternal term sera and control sera, whereas the sera of women with premature deliveries had a significantly lower mean concentration when compared to the other two groups (P < 0.05). The Kruskal-Wallis
b FIG. 1. Distribution of IgD term deliveries, and premature
i
concentration deliveries.
6 in sera from
PREMATURE
n=22
i
IgD
control
i
mg%
(nonpregnant)
women,
women
with
I2
KRETSCHMER
ET
Al
analysis. on the other hand, disclosed no significant difference of the mean IgD concentration in the three groups (P > 0.05). Individual values in these three groups followed a trimodal pattern of distribution (Fig. 1I. Correlations Gestational uge arrd +tleight c?fproduct. A highly significant exponential correlation was found between maternal IgD levels and gestational age (Y = 10.8 I. P < 0.001) (Fig. 2). Since as expected, birth weight of the product also correlated exponentially with the duration of pregnancy (P < O.OOS), a similar correlation was detected between maternal IgD levels and weight of their products (r = +0.63, P < 0.00 1). Yet, there was no correlation between maternal IgD concentration and birth weight of the product when only term deliveries were considered (u = +0.40, P > 0.05). Parity. Parity ranged from 1 to I.5 with propositi in all groups. ‘There was no correlation between concentration of IgD in maternal term sera and parity. Maternal age. Maternal age ranged from I6 to 42 yr (mean 26.6 yr) in this study. A discrete correlation was found between IgD concentration in term sera and maternal age using a quadratic model (r = +0.53. P < 0.051, while there was no correlation between IgD concentration and age in the control group.
LXeOlONL
MODEL I
6.0 1 -I
= 72 r = odl (+I p
+ =cAl.cuLATLD x 5.03 _ E n ii E c
l
=oeSEnvE0
(lIEAll)
I t
4.0/
-
I
l
/+
E
z m E 0
/+
3.0-
0
-_
.
2.0-
,:’
+/+
.
”
.
ty +I+
l.O-
2’
l
.
;_
/+
l /+
/. l At
.
+’ .
I
25
I
26
I
I
I
I
I
27
26
29
30
31
I
32
11
33
I1
34
35
11
36
37
I
36
39
I
I
40
4l
I
42
~ESTATIOWAL FIG. 2. Exponential correlation between arithmetic mean of observed values for least square roots method.
maternal IgD each gestational
levels week
I
‘
43
44 16E
and gestational age at delivery. is plotted. Calculated values
(we.tv) by
The the
IgD
IN
PREGNANCY
13
HL-A discrepancy. There was no correlation between concentration of IgD in maternal term sera and the six conventionally chosen degrees of HL-A disparity between mother and fetus. ABO and Rh Incompatibility Six instances of ABO and one of Rh (D) incompatibility (this coinciding with an A/O incompatibility) were detected among the 50 term deliveries. Maternal IgD levels in these six cases were among the highest in the study (6.0, 5.6, 5.6, 5.2, 2.4, and 0.64 mg/lOO ml), with a mean IgD of 4.26 mg/lOO ml. The lowest IgD concentration in this group was that of the maternal-fetal pair with double (AO/RhD) incompatibility. Statistical analysis of these results by means of the Mann-Whitney U test, however, did not reveal them to be significant when compared to the remnant 44 term deliveries (mean IgD concentration 2.82 mg/lOO ml). HL-A Specijicities The association of HL-A specificities and IgD concentration in maternal term sera was studied by distributing the latter in four groups ( + 2 SD, + 1 SD, - 1 SD, and - 2 SD) and establishing the independent incidence of maternal and fetal HL-A specificities in each group. Also, sets of HL-A specificities present in the mother and absent in the fetus, or vice versa (HL-A discrepancy sets), were identified and their incidence established in each of said four groups of IgD concentration in maternal serum at term. Using the former approach it was found that maternal HL-A-2 was discretely associated with IgD levels above the mean (P < 0.05) whereas maternal HL-A-13 had a slightly stronger association with IgD levels below the mean (P < 0.01). No fetal HL-A specificity seemed to associate significantly with any maternal IgD level. Furthermore, no set of HL-A discrepancy was associated with any of the four IgD levels chosen for this analysis. DISCUSSION
Our data on IgD concentration in adult nonpregnant women are similar to that of other publications (lo-12,14,15,30,3 l), and the trimodal distribution of individual values in all groups clearly confirmed Rowe’s original observation (2). On the other hand, the lower levels of maternal IgD in premature deliveries and the normal levels of IgD at term are at variance with other studies, where an elevation of IgD in late pregnancies-and normal levels in early pregnancies- has been consistently found (10,14,15). The reason for this discrepancy is not clear but differences in the time of obtention of the blood samples (pre- and postexpulsion) could be of critical importance (10,32). Furthermore, our survey was performed with Mexican-mestizo women of low socioeconomic status, whereas reports in the literature concern either Anglo-Saxon (14,15) or Negro patients ( lo), so that the discordant results could also be explained by an ethnic difference in the control of IgD concentration during pregnancy. Germane to this is Colwel’s observation that Vietnamese and Montagnard patients with malaria had distinctly elevated levels of IgD, while these remained normal in Cambodian patients (33).
14
KRETSCHMER
ET
AL..
In spite of these discrepancies, pregnancy was not without effect to maternal IgD concentration, even in our survey, as revealed by the highly significant exponential correlation between gestational age and maternal 1gD levels. Since weight of the product did not correlate with maternal IgD concentration in term deliveries, other phenomena associated with the cumulative effect of a growing conceptus are likely to be relevant to the peculiar behavior of 1gD during pregnancy ( 10,14). It has been proposed that elevated IgD levels in maternal sera at term represent antibodies directed either against leukocyte or trophoblastic antigens (14), and a factor can frequently be found in plasma of pregnant women which is capable of inhibiting mixed leukocyte cultures (34.35). A very attractive possibility is that this factor could belong to the IgD class. Our study, however,. did not disclose any significant correlation between maternal IgD levels at term and HL-A or blood-group maternal-fetal disparities. Since the survey waq limited to only a few antigenic specificities, further studies seem warranted to define the possible influence on maternal IgD levels of antigenic stimulation of the mother by the fetus. On the other hand. certain specificities in the mother (HL-A-2 and HL-A- 13) seemed to influence maternal IgD levels irrespective of their presence in the fetus. Again the limited character of this study precludes the assumption that these allotypes are. in fact, associated with the control 01 serum concentration of IgD, but the observation deserves further study. Finally. there was no correlation between IgD levels and parity in our survey. as opposed to Leslie’s observation (10) that women who had multiple pregnancies have more IgD than those who have not been previously pregnant. Again. an ethnic factor could account for these discordant results. The discrete correlation of maternal IgD levels and age in term deliveries contrasts with the lack of correlation between IgD levels and age in controls. Although the biological significance of this observation is obscure, it is not the first instance where an age dependency of IgD levels has been found (3). ACKNOWLEDGMENT We thank
Mr.
Rafael
Ronces
for his excellent
assistance
in the statistical
evaluation
of the result\
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16. 27. 28. 29. 30. 3 I. 32. 33. 34. 35. 36.
IN
PREGNANCY
15
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