Plasma levels of the immunomodulatory cytokine interleukin-10 during normal human pregnancy: a longitudinal study

Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve foetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p<0.05, p<0.01 and p<0.0001, respectively), and in mothers post-delivery (p<0.01) when compared to non-pregnant control subjects. Furthermore, there was no significant effect of gestational time on IL-10 concentration. Results from the current study suggest that elevated IL-10 is a physiological consequence of normal healthy pregnancy. These findings help clarify previous conflicting results and establish a range for plasma levels of IL-10 in normal healthy pregnancy.     

Collection of anti-D immune plasma after labor. Apropos of 4370 plasmaphereses

4 370 plasmaphereses have been realized on women in the post delivery period for collection of immune anti-D plasma. 1.550 liters of such plasma have been collected and submitted to Cohn fractionation, leading to the preparation of about 100 000 vials of 100 micrograms. Thus, most of the Paris area needs for anti-D IgG have been covered for the past 13 years. Medico-legal aspects of blood donation at this particular period of a woman's life and proper motivations of these donors are underlined. Prospects for this type of blood collection are analyzed as a conclusion.     

Iron and copper concentrations in the maternal and fetal serum, placenta and amniotic fluid during the reproductive stadium as well as in the milk of rabbits

Serum concentrations of iron and copper from rabbits (New Zealand White hybrids; N = 12) were determined during the reproductive stadium (gestation and four weeks of lactation). Samples of serum from fetuses, placental tissue and amniotic fluid were also examined. Iron: a decrease of iron in the maternal serum during the second half of gestation was observed, whilst a significant rise occurred in the first week of lactation. The content of iron in the fetal serum dropped from day 21 to day 28 of gestation. The iron concentration in the placental tissue decreased during this time. A rise of the iron level in the amniotic fluid was determined from day 21 to day 28 of gestation. The iron content in the milk was about 33 mumol/l (first and second day of lactation). Copper: in the first half of pregnancy the copper level diminished slightly compared with the content of non-pregnant, non-lactating rabbits, while a rise was observed in the fourth week of this period. The copper concentration decreased in the first week of lactation and then reached the peak level in the second week of this phase. The copper level in the fetal serum declined from day 21 to day 28 of gestation, while the copper content in the amniotic fluid increased significantly on day 28, in comparison with day 21 of gestation. In contrast, a decline of the copper concentration in the placental tissue was noticed from day 21 to day 28 of this period. The copper content in the milk was nearly 25 mumol/l (first and second day of lactation).     

Cortisol and susceptibility to malaria during pregnancy

We measured cortisol and prolactin concentrations in the peripheral venous blood of 23 non-pregnant and 59 pregnant Gabonese women from the second trimester of pregnancy until delivery. Cortisol concentrations were significantly higher in primigravidae women than in multigravidae women between 20 and 25 weeks' gestational age (166 vs. 132 ng/ml, respectively), between 28 and 37 weeks (226 vs. 161 ng/ml) and at delivery (287 vs. 188 ng/ml). Conversely, plasma prolactin levels were highest in multigravidae women. Cortisol and prolactin concentrations both increased with the period of pregnancy (P = 0.01 and P < 0.01, respectively), suggesting that a sustained increase in cortisol level underlies the increased susceptibility of pregnant women, particularly primigravidae women, to malaria. In support of this hypothesis, we found a significant association between cortisol concentration and Plasmodium falciparum infection, on the one hand, and strong correlations with parasite load in P. falciparum-infected primigravidae women, on the other hand (rho between 0.35 and 0.45 with P < 0.01).     

Seasonal variations of plasma prolactin and LH concentrations in the female blue fox (Alopex lagopus)

A heterologous radioimmunoassay system developed for the rabbit and suitable for a wide range of mammalian species has been shown to measure prolactin in the plasma of the blue fox. Evaluation of prolactin levels throughout the year showed the concentrations displayed a circannual rhythm with the highest values occurring in May and June. Prolactin concentrations remained low (approximately 2.5 ng/ml plasma) from July until April with no consistent changes found around oestrus (March-April). In 8 pregnant females, the prolactin increase in late April and May coincided with the last part of gestation and lactation: concentrations (mean +/- s.e.m.) increased to 6.3 +/- 0.6 ng/ml at mid-gestation, 9.7 +/- 2.1 ng/ml at the end of gestation and 26.7 +/- 5.0 ng/ml during lactation. In 10 non-pregnant animals, the mean +/- s.e.m. values were 7.2 +/- 1.2 ng/ml in April, 8.8 +/- 2.2 ng/ml in May and 9.8 +/- 1.3 ng/ml in June. The prolactin profile in 4 ovariectomized females was similar to that observed in non-pregnant animals, but the plasma values tended to be lower during the reproductive season (April-June). In intact females, the only large LH peak (average 28 ng/ml) was observed around oestrus. During pro-oestrus, baseline LH levels were interrupted by elevations of 3.1-10.4 ng/ml. During the rest of the year, basal levels were less than 3 ng/ml. In ovariectomized females, LH concentrations increased within 2 days of ovariectomy and remained high (35-55 ng/ml) at all times of year.     

Corticotropin releasing hormone concentrations in umbilical cord blood of preterm fetuses.

Corticotrophin releasing hormone (CRH), dehydroepiandrosterone sulfate (DHEAS) and cortisol were measured in umbilical cord plasma obtained from 90 preterm and 98 term fetuses. Maternal plasma was obtained from 23 women who delivered preterm and from 23 women matched for gestational age who ultimately delivered term infants. Mean umbilical cord plasma CRH concentration was significantly higher in the preterm fetuses (n = 69, 538 +/- 63 pg/ml) compared to the term fetuses (n = 98, 280 +/- 22 pg/ml, P < 0.01). Mean DHEAS level in the preterm fetuses was 208 +/- 22 mg/dl (n = 56), cortisol level was 7 +/- 1 mg/dl (n = 58). Umbilical plasma CRH concentrations (808 +/- 170 pg/ml) were significantly higher at 24-27 weeks than at 28-31 or 31-34 weeks gestation. Cortisol levels (12 +/- 3 micrograms/dl) were highest at 24-27 weeks. Mode of delivery and the presence of labor did not affect fetal CRH levels. The highest fetal CRH levels were measured in the pregnancies complicated by hypertension as well as prematurity; however, fetal CRH levels remained higher in the preterm group compared to the term group when hypertensive pregnancies were excluded. Maternal plasma CRH levels were significantly higher in the group that delivered preterm compared to women who delivered at term matched for gestational age (1058 +/- 184 pg/ml compared to 456 +/- 71 pg/ml, P < 0.00).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.

OBJECTIVE--To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN--Open study with historical controls. SETTING--Multicentre study in 17 hospitals in West Yorkshire. PATIENTS--1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS--Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS--Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS--Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS--Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.     

Characterization of the major steroids present in amniotic fluid obtained between the 15th and 17th weeks of gestation

In pooled amniotic fluid obtained between the 15th and 17th weeks of gestation the concentration of free steroids and steroid glucuronides was found to be 40 micrograms/dl. The concentration of steroid monosulfates and disulfates was 19 micrograms/dl. About half of the characterized steroids are progesterone metabolites. The "fetal type" 3 beta-hydroxy-5-ene steroids were found exclusively in the sulfoconjugated form. Their concentration represents 20% of the total steroid content. The identification of two 15 beta-hydroxylated C21 steroids, 3 beta,15 beta,17 alpha-tridoxy-5-pregnen-20-one and 5-pregnene-3 beta,15 beta,17 alpha,20 alpha-tetrol isolated from mid-pregnancy amniotic fluid is reported here. Metabolites of cortisol and 17-deoxycorticosteroid metabolites had similar quantitative importance, 8.6 and 9.4%, respectively.     

The ACTH content of plasma in fetal and newborn swine]

ACTH concentration has been estimated radioimmunologically in fetal plasma (100th day of gestation) and in plasma of newborn piglets during the first 24 hours of life and in sows. In comparison to the values of ACTH in sows at the 100th day of gestation during anaesthesia (175 pg/ml) and sows at parturition (235 +/- 77 pg/ml) the concentration in fetal (558 +/- 163 pg/ml) and newborn piglets (448 +/- 158 pg/ml) was much higher. On an average ACTH concentration increased during the first 24 hours of life up to 998 +/- 628 pg/ml. The results are compared to those in other species.     

A triplet pregnancy after gonadotropin-releasing hormone pulsatile infusion therapy in a postoperative case of growth hormone-producing pituitary macroadenoma

Intravenous GnRH pulsatile infusion therapy (10 micrograms/pulse, 90-min interval) was conducted in an acromegalic patient from whom 2/3 of a GH-producing pituitary macroadenoma had been removed. Before infusion therapy, plasma levels of GH and PRL were 10-20 and 15-25 ng/ml, respectively, while those of LH and FSH were subnormal without intrinsic fluctuations. Ovulation was induced after 13 days of infusion which was terminated on the 23rd day of therapy. Luteal function was supported by hCG (5,000 IU per dose) which was given 4 times from the 23rd to the 31st day of the treatment cycle. Triplet pregnancy was diagnosed ultrasonographically within 7 weeks of gestation. Although GH and PRL levels increased gradually as the gestational period progressed and plasma levels of GH and PRL of 32-55 and 30-67 ng/ml, respectively, were detected after 30 weeks of gestation, neither adverse signs related to the enlargement of the residual pituitary tumor nor manifestation of acromegaly was observed. The immunoreactive somatomedin-C levels during this period were not greater than those in normal pregnant women. Caesarean section was performed at 34 weeks and 3 normal healthy infants were delivered. Detailed analyses of hormonal changes throughout the period of GnRH pulsatile infusion and subsequent luteal phase revealed that the triplet pregnancy had been induced by the GnRH therapy itself and that hCG stimulation did not play any critical role. The residual tumor mass secreted increasing amounts of GH during the latter period of pregnancy but the somatomedin-C levels were not associated with this elevation. Therefore, the clinical as well as the hormonal findings strongly suggested that the GH secreted in increasingly large amounts by the residual tumor mass during pregnancy was defective in certain biological properties.     

Peripheral plasma progesterone and utero-ovarian prostaglandin F concentrations in the cow around parturition.

The concentration of prostaglandin F in utero-ovarian venous plasma and proseterone in jugular venous plasma were determined by radioimmunoassay in 3 cows over the last 2-3 weeks of gestation. Utero-ovarian prostaglandin F concentrations did not show and consistent pattern in two hours of three cows until 48-72 h before term when the levels rose sharply from 1 ng/ml to maximum 4-9 ng/ml during labour. The concentration of prosterone in jugular venous plasma tended to fall gradually over the last 20 days of gestation with a further fall occurring 48-36 h before delivery.     

Use of anti-idiotypic antibodies as probes for the interaction of TSH subunits with its receptor

TSH is a heterodimeric glycoprotein hormone, whose dissociated subunits are without biological activity. This has precluded the assessment of the relative contribution of each subunit to hormone action. We have raised anti-idiotypes to monoclonal antibodies specific, respectively, for the alpha and beta hTSH subunits. The anti-beta anti-idiotype inhibited 125I-hTSH binding to the beta subunit-specific monoclonal quantitatively, whereas 125I-hTSH binding to the alpha subunit-specific monoclonal was not inhibited by anti-alpha anti-idiotypes, suggesting that only the former is an "internal image" anti-idiotype. Neither of the two anti-idiotypes nor equimolar mixtures thereof inhibited 125I-bTSH binding to thyroid membranes, even though radiolabelled anti-idiotypes showed saturable binding to thyroid plasma membrane which was inhibited 41-65% by bTSH. Each anti-idiotype alone caused 9% inhibition (compared to 50% by NRIgG) of thyroid plasma membrane adenylate cyclase. Equimolar mixtures (125 micrograms/ml IgG of each anti-idiotype) induced enzyme activity equivalent to 85% of that of 250 mU/ml of TSH. The TSH-like action of the two anti-idiotypes was also reflected in their capacity to increase (450% by 250 micrograms/ml IgG compared to normal rabbit IgG) the uptake of 131I into isolated thyrocytes and to promote the organization of such cells into follicular structures. At 250 micrograms/ml, anti-beta anti-idiotype promoted the organization of small follicles and only at a concentration of 500 micrograms/ml did it enhance 131I uptake.     

Significance of exercise and bed rest in pregnancy--pregnancy and walking (1)

Prior to evaluating the significance of bed rest in managing obstetric diseases, characteristics of physiology of pregnant women were examined on the basis of 24 hours heart rate changes in eight pregnant women at the third trimester and also distances covered in walking by a total of 53 multiparas and of 87 primiparas during free-living daily activities were measured by means of a pedometer. A significantly higher mean heart rate was observed in those pregnant women even during sleep than in non-pregnant control. The primiparas showed significant decreases in the pedometer readings in all stages except for 15-27 weeks of gestation, while the multiparas of less than 28 weeks exhibited no decrease as compared with non-pregnant control. The decrease in the pedometer readings were marked in both primiparas and multiparas, the value being much lower than that of any other week of gestation. However, the equation of weight x distance covered in walking remains rather constant throughout gestation.     

Comparison of the opsonic and complement triggering activity of human monoclonal IgG1 and IgM antibody against group B streptococci.

We have compared the opsonic and complement-triggering activity of transfectoma-derived, class-switched human IgG1 and IgM mAb (HumAb) against types Ia, II and III group B streptococci (GBS). These antibodies appear to be directed against the common group B cell wall Ag of these organisms. The HumAb IgM promotes uptake of type Ia and II GBS at concentrations as low as 37 ng/ml and type III GBS at concentrations of 150 ng/ml in the presence of human neonatal complement. In contrast, the IgG1 GBS HumAB showed no detectable opsonic activity in concentrations up to 600 ng/ml. When the concentration of HumAb IgG1 is raised to 2.5 micrograms/ml, significant opsonic activity against GBS is detected and when the concentration is approximately 40 micrograms/ml, the opsonic activity peaked at a slightly higher level than that with the HumAb IgM. Thus, approximately 100- fold higher concentrations of the IgG1 than the IgM HumAb are required for optimal opsonization. The opsonic activity of the IgM and IgG1 HumAb are closely related to their ability to consume complement and deposit C3 on the surface of type Ia, II, and III GBS (r = 0.959). We believe that the marked opsonic and protective activity of the IgM GBS HumAb is due to its enhanced avidity and ability to trigger the complement system. Further studies are indicated to determine the feasibility of employing human IgM antibody preparations in the immunotherapy of neonatal GBS disease.     

Peripheral plasma progesterone and utero-ovarian prostaglandin F concentrations in the cow around parturition

The concentration of prostaglandin F in utero-ovarian venous plasma and progesterone in jugular venous plasma were determined by radioimmunoassay in 3 cows over the last 2–3 weeks of gestation. Utero-ovarian prostaglandin F concentrations did not show any consistent pattern in two of three cows until 48–72 h before term when the levels rose sharply from 1 ng/ml to a maximum 4–9 ng/ml during labour. The concentration of progesterone in jugular venous plasma tended to fall gradually over the last 20 days of gestation with a further fall occurring 48-36 h before delivery.In two other cows at around 240 days of gestation the concentration of plasma progesterone in ovarian venous plasma was 50 to 150 times the concentration of progesterone in uterine or jugular venous plasma. It is concluded from these results that the ovaries are the major source of progesterone in cows during late pregnancy. The findings also suggest that prostaglandin F may be the luteolytic factor responsible for the sharp decline in plasma progesterone concentrations over the last 48-36 h preceding parturition.     

Levonorgestrel and norethindrone alter insulin action on skeletal muscle of the female rat

Prospective studies of women receiving oral contraceptives suggest that the progestin component may induce insulin resistance and variable deterioration of glucose tolerance. Because the tissue sites and nature of this insulin antagonism are not well-defined, we studied the effects of two parenterally administered progestins, levonorgestrel (NG) and norethindrone (NE), on insulin-regulated glucose uptake and phenylalanine release by the perfused rat hindquarter. Female rats were injected sc for 14 days with NG or NE (10 or 30 micrograms/kg/day). Low-dose NG and high-dose NE approximate the per kg dose received by women taking a high-dose progestin oral contraceptive. Phenylalanine release and glucose uptake (nmole/min/g) by the perfused hindquarters were calculated from the A-V difference for each. Progestin treatment (30 micrograms/kg/d) significantly reduced phenylalanine release from hindquarters perfused without exogenous insulin. Hindquarters from the high dose NG and low and high dose NE rats perfused with insulin (100 microU/ml) released 22% less phenylalanine than control rats perfused with the same insulin concentration (P less than 0.01) but the net suppression below baseline was similar in the control and steroid-treated groups. High-dose progestin treatment did not alter glucose uptake by hindquarters perfused without exogenous insulin. Insulin (100 microU/ml) increased glucose uptake by hindquarters of control and progestin-treated rats as compared to animals in the same treatment group perfused without exogenous insulin (P less than 0.01). High dose NE impaired insulin-stimulated glucose uptake 24% below values of the control group (P less than 0.01). The other NE and NG doses had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

一种改进的异硫氰酸胍法结合硅胶膜离心吸附柱提取孕妇外周血微量胎儿RNA的方法

孕妇外周血中存在胎儿RNA为无创性产前诊断提供了基础.但血液中富含RNA酶和微量胎儿RNA的特点,对从孕妇血浆中提取胎儿RNA带来困难. 我们以ε血红蛋白基因和胎盘特异表达基因4（PLAC4）mRNA作为研究对象,用改进的异硫氰酸胍法结合硅胶膜离心吸附柱法探索孕妇外周血中胎儿微量RNA的提取方法,获得满意效果. 30例孕妇和9例非孕妇外周血样品中总RNA经凝胶电泳测定显示3条带,分别为28S, 18S和 5.8S. 其28S条带亮度为18S亮度的2倍.总RNA质量浓度（A260／A280）为1.97 g/L,光密度比值(A260-A320）/（A280- A 320）为1.86. 30例孕妇外周血样本有7例提取到ε血红蛋白基因mRNA,ε血红蛋白基因 mRNA 的最小浓度为0.537 μg/mL,最大浓度为1.79 μg/mL,ε血红蛋白基因mRNA的浓度中位数为124 μg/mL. 30例孕妇外周血样本提取到PLAC4 基因mRNA,浓度最小值为2.105×103 copies/mL,最大值为12.760×103 copies/mL,而9例非孕妇中均未提取到（P＜0.01）,浓度中位数为6.612×103 copies/mL. 因此,改进的异硫氰酸胍法与硅胶膜离心吸附柱纯化法相结合,可有效抑制RNA降解,用于提取、纯化孕妇血液中微量胎儿RNA.     

Elevated leptin concentrations in pregnancy and lactation: possible role as a modulator of substrate utilization.

Energy needs are increased during pregnancy and lactation. These increased energy needs may be met through partitioning of nutrients for energy utilization which is under hormonal control. The objective of the present studies was to determine if changes in plasma leptin occurred during pregnancy and lactation and if the changes were related to prolactin. Plasma leptin and prolactin were measured longitudinally in 9 women through pregnancy and lactation. In a second study, leptin and prolactin were measured 4 days and 28 days postpartum in 21 lactating women. Mean plasma leptin during the three trimesters of pregnancy was significantly higher (29.3+/-2.8 ng/ml) when compared to mean leptin during the three time periods of lactation (19.3+/-3.2 ng/ml) and control groups (9.8+/-1.4 ng/ml). Plasma leptin was elevated early in pregnancy and remained elevated throughout pregnancy. In the second study, the mean plasma leptin in the lactating women was significantly higher 4 days postpartum (17.3+/-3.7 ng/ml) and 28 days postpartum (19.2+/-3.9 ng/ml) when compared to controls (11.6+/-1.2 ng/ml). Prolactin in the control subjects (24+/-4 ng/ml) was significantly lower than in the pregnant (202+/-16 ng/ml) and lactating (108+/-26 ng/ml) groups. Similar observations were made in the second study (controls 20+/-2 ng/ml; lactation 28 days 159+/-21 ng/ml). Leptin during lactation was lower than in pregnancy but higher than control subjects. Regression analysis suggested that BMI and prolactin can be used as predictors of leptin in pregnancy and lactation. The increase in leptin and prolactin early in pregnancy suggests an association between the two hormones. Results of the present studies and research done by other investigators presents a strong role for leptin during pregnancy and lactation. Leptin is regulated by factors other than adiposity especially in reproductive women leading to our hypothesis that there are leptin and prolactin mediated effects on substrates used for energy utilization during pregnancy and lactation.     

Absorption of non-haem iron from food during normal pregnancy.

OBJECTIVE--To determine whether the increased iron demands of pregnancy could be met by increased absorption from dietary sources. DESIGN AND SETTING--Longitudinal prospective study in the research unit of a maternity hospital. SUBJECTS--12 normal pregnant women. INTERVENTIONS--At 12, 24, and 36 weeks'' gestation (within one week) and 16-24 weeks after delivery women ate a breakfast of meat, bread, and orange juice (3.2 mg iron), extrinsically labelled with the stable isotope iron-54 (2.8 mg); the stable isotope iron-57 (200 micrograms) was given intravenously. MAIN OUTCOME MEASURES--Serum samples were taken for 10 hours after administration of the isotopes; ratios of the isotopes were measured by inductively coupled plasma mass spectrometry, and the absorption of oral iron was calculated. RESULTS--The geometric mean (95% confidence interval) absorption of iron at 12, 24, and 36 weeks'' gestation was 7% (5% to 11%), 36% (28% to 47%), and 66% (57% to 76%) respectively. At 16-24 weeks after delivery the absorption was 11% (6% to 21%). The mean increase in absorption at 36 weeks (compared with that at 12 weeks) was 9.1 times (6.0 to 13.7). One pregnant woman developed iron deficiency anaemia but was otherwise indistinguishable from the others. CONCLUSIONS--An increase in the absorption of iron from food is a physiological consequence of normal pregnancy, not the result of developing anaemia during pregnancy, and such an increase is large enough to meet the increased requirements of pregnancy provided that the dietary intake is adequate.     

Local production of IgG4 in human colostrum

Total IgG4 levels were determined in 27 colostrum and 27 plasma paired samples by using RIA techniques, and total IgG was determined on the same pairs by using radial immunodiffusion. In colostrum, the mean IgG4 level was 4.6 micrograms/ml (0.6 to 19.0), and in the plasma the mean IgG4 level was 170.5 micrograms/ml (30 to 920). IgG averaged 42.3 micrograms/ml (12 to 240) in colostrum and 7980.9 micrograms/ml (3250 to 16,000) in plasma. Of colostral IgG, 15.3% was IgG4, whereas only 3.5% of plasma IgG was IgG4. Specific IgG4 antibodies to beta-lactoglobulin, bovine serum albumin, bermuda grass, and alpha-gliadin were also assayed. In six patients, strong evidence was found for local mammary production of IgG4-specific antibodies.