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Serum kappa and lambda light immunoglobulin chains in cynomolgus macaques (Macaca fascicularis) during the first twenty months of age
Immunology Letters 50 (1996) 139- 142
ELSEVIER
Serum kappa and lambda light immunoglobulin chains in cynomolgus macaques (Macaca fascicularis) during the first twenty months of age Monica Pacea,*, Maria Concetta D’Ovidioa,b, Elio Iale”, Roberto Stromb, PierGiovanni Turillazzi” “Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanitir, Viale R. Elena, 299-00161 bDepartment of Human Biopathology, ‘La Sapienza’ University, Rome, 1tal.y
Rome, Italy
Received 7 February 1996; accepted 16 February 1996
Abstract
Growth is coupled to physiological modifications of the immune system which reaches the functional capabilities according to age-related milestones. Few data are available on the circulating immunoglobulin levels and no data exist on total immunoglobulin light chains in infant macaques. Therefore we studied by a nephelometric assay, the age-dependent variations of K and /1 serum light chains in the experimental animal model Mucaca fascicularis during the first 20 months of age. Both z and E.showed a marked increase in their concentrations during the first 7-8 months of life. Infants’ light chain levels were anyhow significantly lower than those of the nursing dams and of the control group, never attaining, even at the 20th month, the same concentration as the adult, although the value of the ~//i ratio was apparently the same. Keywords:
Light immunoglobulin
chains; Acquisition
of immunocompetence;
1. Introduction The maturation of the immune system is known to occur gradually, some Igs being present in serum, at birth, in different concentrations. This is in part due to the physiologic differences among each Ig class concentration shown by the adult subjects, and in part to the IgG-restricted transplacental passage during pregnancy, that contributes to a rise in the detectable level of this Ig class at birth [ 1,2]. In macaques, as in humans, every single Ig class reaches adult serum levels at different periods of postnatal life [2-41. As a direct consequence, also light chains bound to all circulating Igs follow an age-dependent trend. This has been well documented in humans during the first two decades of life [5-71. while
* Corresponding 4440140. 0165-2478/96/$12.00
author.
Tel.:
+ 39 6 49902313; fax:
+ 39 6
Q 1996 Elsevier Science B.V. All rights reserved
PII SO165-2478(96)02522-9
Macaca fascicularis;
h-/A
ratio; Nephelometric
assay
little is known in the experimental model Macaca fascicufuris, where a single study on adults’ total immunoglobulin light chains has so far been reported [9]. At present, only data on Igs during early life are available in macaques [3,4,10], while light chains have not been taken into consideration. It is instead important in our opinion, to add new data regarding immunoglobulin light chains in order to have an adequate characterization of the humoral immunological status in macaque species, to be used as reference values in pathologies leading to alterations of the B-lymphocyte compartment. The aim of this report was to provide the first characterization of the total light immunoglobulin chain serum levels in young individuals of cynomolgus macaques from 0 to 20 months of age, when the lack of full lymphocyte competence is likely to confer a higher susceptibility to infections. A better understanding of how complete functionality of the immune system is attained will ensure a better utilization of valuable animal models such as non-human primates.
140
M. Pace et al. / Immunology Letters 50 (1996) 139-142
2. Materials and methods 2.1. Subjects This study was performed on newborns, infants and juvenile cynomolgus monkeys (Macaca fusciculuris) of age comprised between 0 and 20 months of life. The subjects were grouped in ten age-classes, as shown in Table 1. The data were analyzed on a time-scale, to evaluate the light chain trend in immature individuals, and were also compared with the values obtained from nursing females (D’Ovidio et al. accepted, [8]) as well as in a control group of 23 healthy adults [9]. The newborn subjects were born at Istituto Superiore di Sanita, in Rome. They were kept indoor with their mothers, in stainless steel cages, until weaning. At their 7th month of age, the infants and their mothers were transferred to a different environment where they had enhanced interactions with other mother-infants diads. All weaned and adult subjects were fed with Monkey Chow on a daily basis, fresh fruit was supplied twice a week; water was suppiled ad libitum. 2.2. Sampling Prior to blood sampling, all the experimental subjects were sedated with Ketamine HCl (10 mg/kg i.m. for the adults, 5-7 mg/kg i.m. for the infants). Blood sampling was performed in the morning (8.00-10.00 a.m.), the adult subjects having been fasted overnight. The first blood samples were collected in newborns within the first month of life and once every month thereafter. The sampling in the nursing mothers was performed monthly in order to obtain a comparable set of data with the age-class of the immature subjects; the mean of each two months determination was then calculated and utilized for the statistical analysis. Only one sampling was performed in the 23 control adults, as reported in D’Ovidio et al. [9]. All blood samples were collected in glass tubes and centrifuged at 3000 rev./min. Sera were stocked at - 80°C until used for light chain determinations. 2.3. Determination technique An immunonephelometric procedure, using the Behring automated Laser Nephelometer, (Behringwerke, Marburg, Germany) was utilized for determination of total K and 1 immunoglobulin light chain concentrations. Standard and control sera and antisera were provided by Behringwerke. Both standard and control sera, obtained from healthy human volunteers were supplied by the manufacturer, while antisera to human
total (free and bound) K and /z light chains were obtained after rabbit immunization. Rabbit antisera is the most widely used for Igs and light chains quantification in non-human primates [9,11]. A six-point standard dilution pattern (1:5, l:lO, 1:20, 1:40, 180, 1:160) was used to assess the light chain levels in each sample. 2.4. Statistics Since the two-tailed Mann-Whitney test between sexes was not significant within each age-class. the overall differences during the 20 months of the study were assessed by the non-parametric Kruskal-Wallis test on each determination, regardless of individual sex. To verify where the significance occurred, a twotailed Mann-Whitney test between each age-class was performed after the analysis of variance. Mean values of each age-class were tested against mean values of both control groups for each parameter. These comparisons were performed by the twotailed Mann-Whitney test. Level of significance was set at P I 0.05. The values of each immunological parameter of the youngsters were compared to those of the nursing females and of the adult group, and expressed as percentages.
3. Results No sex differences were evidenced in any age-class for each parameter (data not shown). These results are in accordance with those reported on adults from the same colony [9]. Age-dependent variations of immunoglobulin light chains are reported in Table 1. The Kruskal-Wallis test during the first 20 months of age was highly significant for K (H = 29.84; P = O.OOOS),and for 2 chains (H = 34.23; P = O.OOOOS), but not for the K/A ratio (H = 2.29; n.s.). The Mann-Whitney test failed to show, for any parameter significant differences between consecutive age-classes. The values at O-2 months were, however, significantly different from those at 7-8 months of age (for K, U = 48; P = 0.03; for 1, U = 49; P = 0.02) or at later times. The same was true when the values at 3-4 months were compared to those at 7-8 months (for K, U=117; P=O.O3; for 2, U=122; P=O.Ol) or to values of later samples. The significance level attained was P < 0.01 for both K and /1 chains. The K/A ratio was practically constant throughout the first 20 months of life (Table 1). The values of K and /i light chains concentrations and of the K/A ratio in youngsters were also compared
M. Pace et al. /Immunology Table 1 Variations Age-classes o-2 (4) 3-4 (11) 5-6 (12) 7-8 (14) 9-10 (12) 11-12 (13) 13-14 (10) 15-16 (10) 17-18 (5) 19-20 (6)
of immunoglobulin in months
(N)
light chains x(mG/dL)
Letters 50 (1996) 139-142
in Macaca fascicularis from birth mean
I
SE.
range
65.8 + 4.2 53.4-11.4 68.3 + 4.6 36.9-84.4 79.0 + 7.1 46.4-139.9 109.3 k 18.1 57.4-325.6 117.2 + 17.0 55.4-227.5 108.3 k 9.0 66.8-183.3 104.4 k 8.5 65.3-162.4 114.1 + 11.0 78.8-183.3 116.7fll.2 90.4- 155 118.5 k 15.2 84.5-183.5
to the values of the nursing females, and of a group of adults. The results are shown in Fig. 1. The Mann-Whitney test performed on the first 12 months of age with respect to the nursing females group showed significant differences for K and R light chains from birth on, while no differences were detected for the K/J ratio. The first 6 months of life (when lactation occurred) showed a highly significant difference with respect to the females’ levels, for both K and A (P < 0.001); these two light chains reached respectively, a mean percentage of 34% and 40%. The post-weaning period showed an increment of infants’ light chain values with percentages averaging 60% for K and 65% for /2. In the 6 months following the end of lactation, the level of significance by the Mann-Whitney test, was P < 0.05. No further information could be obtained by comparing the values within same single infant-mother diads, rather than between the infants vs. mothers groups (data not shown). The comparisons with the adult control group showed significant differences among all the age-classes for both K J, chains, not the k-/i.ratio. In during the of life (O-2 the variations of both chains showed the same level of significance (U = 92, P = 0.0001) and a percentage of about 39%. A steep rise in the light chain levels may be noted during the first 7-8 months of life, when they approached a value corresponding to 65% of the adult levels (Fig. 1). Both K and 1 levels remained significantly different from the adult ones until the end of the study, but the /z chain reached a value (75%) closer to the adult one (U = 114; P = 0.0135) than the K chain (70%), (U = 117; P = 0.0077).
to 20
Z.(mG/dL)
141
months of age mean
101.8 f 7.4 82.6- 116.9 109.3 + 9.1 64.2-154.4 122.2 t 12.5 45.7-190.1 163.1 k 21.1 17.7-408.1 169.8 & 19.9 95.5-313.2 168.0 * 9.9 106.3-234.8 168.8 * 7.5 135.6-206.3 167.1 f 8.4 133.4-227.1 182.7 f 16.7 143.1-220.2 197.1 F 13.7 141.2-227.1
f
S.E. range
K/*! mean
& SE.
range
0.65 + 0.05 0.54-0.81 0.64 * 0.03 0.50-0.86 0.65 k 0.04 0.43-0.96 0.64 + 0.03 0.42-0.87 0.68 + 0.04 0.38-0.88 0.64 + 0.03 0.44-0.85 0.61 + 0.04 0.43-0.83 0.64 * 0.04 0.48-0.93 0.64 f 0.05 0.47-0.79 0.60 + 0.01 0.43 -0.80
4. Several pathologies characterized prefsynthesis specific classes subclasses, sometimes a by of K ;1 chain. situation been in cases by in K/A ratio, whose diagnostic value has anyhow been questioned in the case of human infant pathologies due to the presence of passively acquired maternal IgG [2] and to the immature functional capability in the immunoglobulin synthesis in the first years of postnatal life [5-71. A similar IgG behaviour has also been assessed in macaques [13,14] and it is likely that similar limitations of the validity of the K/A ratio may occurr in the early age of these monkeys. When comparing humans to macaques, it is indeed necessary to take into account the existing differences in the normal adult values in the two species. In fact while the human k-j,? ratio is higher than 1, the same ratio is below 1 in macaques, due to the higher i, concentration [9,15]. The K/A ratio during growth is, however, the result of two events: the catabolism of the maternally-derived IgG component and the increased synthesis of Igs by the infant. The isotype of maternal origin is almost completely cleared away in the human species by the 6th month of life, and the infant capabilities to synthetize the IgG class molecules are comparable to those of the adult at about 3 years of life [2]. A somewhat different timing occurs in macaques: in tact, the catabolism of the maternally-derived IgG has been reported to occur within the first 2-3 months of life, while the adult levels are attained relatively late, namely
M. Pace et al. /Immunology Letters 50 (1996) 139-142
142
after the first 3-5 years of age [3,4]. The faster clearance of passively acquired IgG in macaques with respect to humans could make the K/J ratio more reliable in the animal model at an early age; this aspect contributes to validate the macaques as experimental models in the study of several pathologies. Our data on Macaca fascicularis indicate the existence of a progressive increase in the K and A serum levels in the first months of age, i.e. during lactation and weaning period, suggesting important modifications in the B-cells compartment during the first 7-8
months. The infants’ immunocompetence maturation shows in fact, in the first 7-8 months, a steep rise from about 35 to 60-65% for both light chains synthesis; this trend seems to indicate a common influence of the end of lactation on the Igs in toto, regardless of any preferential synthesis of K or 1. After weaning is completed, i.e. by the 9th month, variations in K and R chain levels are relatively small, although even by the 20th month complete immunocompetence is not yet attained, since the levels of K and L chains are still around 72% and 76%, respectively, of the corresponding values in the adults.
Acknowledgements
This work was supported by the Istituto Superiore di Sanita’ research project ‘Prevention of risk factors of maternal and child health’.
References [I] Ricardo, M.J. and Tomar, R.H. (1991) in: Clinical and diagno-
Age-classes
ln months
Fig. 1. Light chain concentrations in the serum of Macacafascicularis from birth to 20 months of age, expressed as percentage of the values vs. nursing dams or vs. adults.
sis management by laboratory methods (J.B. Henry, Ed.), 18 edition, pp. 809-829, WB Saunders Company, Philadelphia. [2] Nevard, C.H.F., Grant, M. and Ockleford, CD. (1990) in: The immunology of the fetus (G. Chaouat, Ed.), pp. 194-214, CRC Press, Boca Raton, FL. [3] Terao, K. (1981) Japan. J. Med. Sci. Biol. 34, 246. [4] Fujimoto, K., Terao, K., Cho, F., Nakamura, F. and Honjo, S. (1982) Jpn. J. Med. Sci. Biol. 35, 17. [5] Renckens, A.L.J.M., Jansen, M.J.H., van Munster, P.J.J., Weemaes, C.M.R. and Bakkeren, J.A.J.M. (1986) Clin. Chem. 32, 2147. [6] Herkner, K.R., Salzer, H., BBck, A., Miihl, A., Tsaka, T., Steger, H., Pollak, A., Schatten, C., Popp. W., Huber-Spitzy, V. and Herkner, C. (1992) Clin. Chem. 38, 548. [7] Saitta, M., Iavarone, A., Cappello, N., Bergami. M.R., Fiorucci, G.C. and Aguzzi, F. (1992) Clin. Chem. 38, 2454. [8] D’Ovidio, M.C., Pace, M., Via, F., Iale, E., Turillazzi, P.G. and Strom, R. (1996) Dev. Comp. Immunol. Accepted for publication. [9] D’Ovidio, M.C., Pace, M., Via, F., Strom, R. and Turillazzi. P.G. (1994) Fol. Primatol. 63, 221. [IO] Fujimoto, K., Terao, K., Cho, F. and Honjo, S. (1983) Japan. J. Med. Sci. Biol. 36, 209. [ll] Shuster, J., Warner, N.L. and Fudenberg, H.H. (1969) Ann. N.Y. Acad. Sci. 162, 195. [12] Gerritsen, E., Vossen. J., Van Tol, M., Jol-Van Der Zijde, C.. Van Der Weijden-Ragas, R. and Radl, J. (1989) J. Clin. Immunol. 9. 296. [13] Fujimoto, K., Terao, K., Cho, F. and Honjo, S. (1983) Japan. J. Med. Sci. Biol. 36, 171. [14] Coe, C.L., Kemnitz, J.W. and Schneider, M.L. (1993) J. Med. Primatol. 22, 294. [15] Laine, S.T., Soppi, E.T. and Miirsky, P.J. (1992) Clin. Chim. Acta 207, 143.
ELSEVIER
Serum kappa and lambda light immunoglobulin chains in cynomolgus macaques (Macaca fascicularis) during the first twenty months of age Monica Pacea,*, Maria Concetta D’Ovidioa,b, Elio Iale”, Roberto Stromb, PierGiovanni Turillazzi” “Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanitir, Viale R. Elena, 299-00161 bDepartment of Human Biopathology, ‘La Sapienza’ University, Rome, 1tal.y
Rome, Italy
Received 7 February 1996; accepted 16 February 1996
Abstract
Growth is coupled to physiological modifications of the immune system which reaches the functional capabilities according to age-related milestones. Few data are available on the circulating immunoglobulin levels and no data exist on total immunoglobulin light chains in infant macaques. Therefore we studied by a nephelometric assay, the age-dependent variations of K and /1 serum light chains in the experimental animal model Mucaca fascicularis during the first 20 months of age. Both z and E.showed a marked increase in their concentrations during the first 7-8 months of life. Infants’ light chain levels were anyhow significantly lower than those of the nursing dams and of the control group, never attaining, even at the 20th month, the same concentration as the adult, although the value of the ~//i ratio was apparently the same. Keywords:
Light immunoglobulin
chains; Acquisition
of immunocompetence;
1. Introduction The maturation of the immune system is known to occur gradually, some Igs being present in serum, at birth, in different concentrations. This is in part due to the physiologic differences among each Ig class concentration shown by the adult subjects, and in part to the IgG-restricted transplacental passage during pregnancy, that contributes to a rise in the detectable level of this Ig class at birth [ 1,2]. In macaques, as in humans, every single Ig class reaches adult serum levels at different periods of postnatal life [2-41. As a direct consequence, also light chains bound to all circulating Igs follow an age-dependent trend. This has been well documented in humans during the first two decades of life [5-71. while
* Corresponding 4440140. 0165-2478/96/$12.00
author.
Tel.:
+ 39 6 49902313; fax:
+ 39 6
Q 1996 Elsevier Science B.V. All rights reserved
PII SO165-2478(96)02522-9
Macaca fascicularis;
h-/A
ratio; Nephelometric
assay
little is known in the experimental model Macaca fascicufuris, where a single study on adults’ total immunoglobulin light chains has so far been reported [9]. At present, only data on Igs during early life are available in macaques [3,4,10], while light chains have not been taken into consideration. It is instead important in our opinion, to add new data regarding immunoglobulin light chains in order to have an adequate characterization of the humoral immunological status in macaque species, to be used as reference values in pathologies leading to alterations of the B-lymphocyte compartment. The aim of this report was to provide the first characterization of the total light immunoglobulin chain serum levels in young individuals of cynomolgus macaques from 0 to 20 months of age, when the lack of full lymphocyte competence is likely to confer a higher susceptibility to infections. A better understanding of how complete functionality of the immune system is attained will ensure a better utilization of valuable animal models such as non-human primates.
140
M. Pace et al. / Immunology Letters 50 (1996) 139-142
2. Materials and methods 2.1. Subjects This study was performed on newborns, infants and juvenile cynomolgus monkeys (Macaca fusciculuris) of age comprised between 0 and 20 months of life. The subjects were grouped in ten age-classes, as shown in Table 1. The data were analyzed on a time-scale, to evaluate the light chain trend in immature individuals, and were also compared with the values obtained from nursing females (D’Ovidio et al. accepted, [8]) as well as in a control group of 23 healthy adults [9]. The newborn subjects were born at Istituto Superiore di Sanita, in Rome. They were kept indoor with their mothers, in stainless steel cages, until weaning. At their 7th month of age, the infants and their mothers were transferred to a different environment where they had enhanced interactions with other mother-infants diads. All weaned and adult subjects were fed with Monkey Chow on a daily basis, fresh fruit was supplied twice a week; water was suppiled ad libitum. 2.2. Sampling Prior to blood sampling, all the experimental subjects were sedated with Ketamine HCl (10 mg/kg i.m. for the adults, 5-7 mg/kg i.m. for the infants). Blood sampling was performed in the morning (8.00-10.00 a.m.), the adult subjects having been fasted overnight. The first blood samples were collected in newborns within the first month of life and once every month thereafter. The sampling in the nursing mothers was performed monthly in order to obtain a comparable set of data with the age-class of the immature subjects; the mean of each two months determination was then calculated and utilized for the statistical analysis. Only one sampling was performed in the 23 control adults, as reported in D’Ovidio et al. [9]. All blood samples were collected in glass tubes and centrifuged at 3000 rev./min. Sera were stocked at - 80°C until used for light chain determinations. 2.3. Determination technique An immunonephelometric procedure, using the Behring automated Laser Nephelometer, (Behringwerke, Marburg, Germany) was utilized for determination of total K and 1 immunoglobulin light chain concentrations. Standard and control sera and antisera were provided by Behringwerke. Both standard and control sera, obtained from healthy human volunteers were supplied by the manufacturer, while antisera to human
total (free and bound) K and /z light chains were obtained after rabbit immunization. Rabbit antisera is the most widely used for Igs and light chains quantification in non-human primates [9,11]. A six-point standard dilution pattern (1:5, l:lO, 1:20, 1:40, 180, 1:160) was used to assess the light chain levels in each sample. 2.4. Statistics Since the two-tailed Mann-Whitney test between sexes was not significant within each age-class. the overall differences during the 20 months of the study were assessed by the non-parametric Kruskal-Wallis test on each determination, regardless of individual sex. To verify where the significance occurred, a twotailed Mann-Whitney test between each age-class was performed after the analysis of variance. Mean values of each age-class were tested against mean values of both control groups for each parameter. These comparisons were performed by the twotailed Mann-Whitney test. Level of significance was set at P I 0.05. The values of each immunological parameter of the youngsters were compared to those of the nursing females and of the adult group, and expressed as percentages.
3. Results No sex differences were evidenced in any age-class for each parameter (data not shown). These results are in accordance with those reported on adults from the same colony [9]. Age-dependent variations of immunoglobulin light chains are reported in Table 1. The Kruskal-Wallis test during the first 20 months of age was highly significant for K (H = 29.84; P = O.OOOS),and for 2 chains (H = 34.23; P = O.OOOOS), but not for the K/A ratio (H = 2.29; n.s.). The Mann-Whitney test failed to show, for any parameter significant differences between consecutive age-classes. The values at O-2 months were, however, significantly different from those at 7-8 months of age (for K, U = 48; P = 0.03; for 1, U = 49; P = 0.02) or at later times. The same was true when the values at 3-4 months were compared to those at 7-8 months (for K, U=117; P=O.O3; for 2, U=122; P=O.Ol) or to values of later samples. The significance level attained was P < 0.01 for both K and /1 chains. The K/A ratio was practically constant throughout the first 20 months of life (Table 1). The values of K and /i light chains concentrations and of the K/A ratio in youngsters were also compared
M. Pace et al. /Immunology Table 1 Variations Age-classes o-2 (4) 3-4 (11) 5-6 (12) 7-8 (14) 9-10 (12) 11-12 (13) 13-14 (10) 15-16 (10) 17-18 (5) 19-20 (6)
of immunoglobulin in months
(N)
light chains x(mG/dL)
Letters 50 (1996) 139-142
in Macaca fascicularis from birth mean
I
SE.
range
65.8 + 4.2 53.4-11.4 68.3 + 4.6 36.9-84.4 79.0 + 7.1 46.4-139.9 109.3 k 18.1 57.4-325.6 117.2 + 17.0 55.4-227.5 108.3 k 9.0 66.8-183.3 104.4 k 8.5 65.3-162.4 114.1 + 11.0 78.8-183.3 116.7fll.2 90.4- 155 118.5 k 15.2 84.5-183.5
to the values of the nursing females, and of a group of adults. The results are shown in Fig. 1. The Mann-Whitney test performed on the first 12 months of age with respect to the nursing females group showed significant differences for K and R light chains from birth on, while no differences were detected for the K/J ratio. The first 6 months of life (when lactation occurred) showed a highly significant difference with respect to the females’ levels, for both K and A (P < 0.001); these two light chains reached respectively, a mean percentage of 34% and 40%. The post-weaning period showed an increment of infants’ light chain values with percentages averaging 60% for K and 65% for /2. In the 6 months following the end of lactation, the level of significance by the Mann-Whitney test, was P < 0.05. No further information could be obtained by comparing the values within same single infant-mother diads, rather than between the infants vs. mothers groups (data not shown). The comparisons with the adult control group showed significant differences among all the age-classes for both K J, chains, not the k-/i.ratio. In during the of life (O-2 the variations of both chains showed the same level of significance (U = 92, P = 0.0001) and a percentage of about 39%. A steep rise in the light chain levels may be noted during the first 7-8 months of life, when they approached a value corresponding to 65% of the adult levels (Fig. 1). Both K and 1 levels remained significantly different from the adult ones until the end of the study, but the /z chain reached a value (75%) closer to the adult one (U = 114; P = 0.0135) than the K chain (70%), (U = 117; P = 0.0077).
to 20
Z.(mG/dL)
141
months of age mean
101.8 f 7.4 82.6- 116.9 109.3 + 9.1 64.2-154.4 122.2 t 12.5 45.7-190.1 163.1 k 21.1 17.7-408.1 169.8 & 19.9 95.5-313.2 168.0 * 9.9 106.3-234.8 168.8 * 7.5 135.6-206.3 167.1 f 8.4 133.4-227.1 182.7 f 16.7 143.1-220.2 197.1 F 13.7 141.2-227.1
f
S.E. range
K/*! mean
& SE.
range
0.65 + 0.05 0.54-0.81 0.64 * 0.03 0.50-0.86 0.65 k 0.04 0.43-0.96 0.64 + 0.03 0.42-0.87 0.68 + 0.04 0.38-0.88 0.64 + 0.03 0.44-0.85 0.61 + 0.04 0.43-0.83 0.64 * 0.04 0.48-0.93 0.64 f 0.05 0.47-0.79 0.60 + 0.01 0.43 -0.80
4. Several pathologies characterized prefsynthesis specific classes subclasses, sometimes a by of K ;1 chain. situation been in cases by in K/A ratio, whose diagnostic value has anyhow been questioned in the case of human infant pathologies due to the presence of passively acquired maternal IgG [2] and to the immature functional capability in the immunoglobulin synthesis in the first years of postnatal life [5-71. A similar IgG behaviour has also been assessed in macaques [13,14] and it is likely that similar limitations of the validity of the K/A ratio may occurr in the early age of these monkeys. When comparing humans to macaques, it is indeed necessary to take into account the existing differences in the normal adult values in the two species. In fact while the human k-j,? ratio is higher than 1, the same ratio is below 1 in macaques, due to the higher i, concentration [9,15]. The K/A ratio during growth is, however, the result of two events: the catabolism of the maternally-derived IgG component and the increased synthesis of Igs by the infant. The isotype of maternal origin is almost completely cleared away in the human species by the 6th month of life, and the infant capabilities to synthetize the IgG class molecules are comparable to those of the adult at about 3 years of life [2]. A somewhat different timing occurs in macaques: in tact, the catabolism of the maternally-derived IgG has been reported to occur within the first 2-3 months of life, while the adult levels are attained relatively late, namely
M. Pace et al. /Immunology Letters 50 (1996) 139-142
142
after the first 3-5 years of age [3,4]. The faster clearance of passively acquired IgG in macaques with respect to humans could make the K/J ratio more reliable in the animal model at an early age; this aspect contributes to validate the macaques as experimental models in the study of several pathologies. Our data on Macaca fascicularis indicate the existence of a progressive increase in the K and A serum levels in the first months of age, i.e. during lactation and weaning period, suggesting important modifications in the B-cells compartment during the first 7-8
months. The infants’ immunocompetence maturation shows in fact, in the first 7-8 months, a steep rise from about 35 to 60-65% for both light chains synthesis; this trend seems to indicate a common influence of the end of lactation on the Igs in toto, regardless of any preferential synthesis of K or 1. After weaning is completed, i.e. by the 9th month, variations in K and R chain levels are relatively small, although even by the 20th month complete immunocompetence is not yet attained, since the levels of K and L chains are still around 72% and 76%, respectively, of the corresponding values in the adults.
Acknowledgements
This work was supported by the Istituto Superiore di Sanita’ research project ‘Prevention of risk factors of maternal and child health’.
References [I] Ricardo, M.J. and Tomar, R.H. (1991) in: Clinical and diagno-
Age-classes
ln months
Fig. 1. Light chain concentrations in the serum of Macacafascicularis from birth to 20 months of age, expressed as percentage of the values vs. nursing dams or vs. adults.
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