Immunoglobulin G subclasses in human colostrum, milk and saliva.

Previous studies have suggested local production of IgG4 in human colostrum and mature milk. We extended these observations to examine all IgG subclasses in mammary secretions and in saliva, a mucosal secretion. In human colostrum and milk, the geometric mean percentages of IgG contributed by IgG2 were 44% and 43%, respectively, and by IgG4, 6% in both. These percentages are significantly increased compared to the contributions in matched plasma, 29% for IgG2 and 2% for IgG4. The contribution of IgG1 (47%) and IgG3 (less than 4%) were decreased compared to plasma which contained 64% IgG1 and 6% IgG3. Similarly, in salivary secretions the percentages of IgG contributed by IgG2 and IgG4 were increased compared to serum while the percentage of IgG1 was decreased. IgG3 was not measurable in any saliva specimen by the technique used. These data demonstrate that IgG subclass distribution in two separate mucosal secretions is uniquely different from that in matching plasma or serum.

IgG4 in human colostrum and human milk: continued local production or selective transport from serum.

Colostrum, mature milk, and paired plasma samples were obtained from 10 postpartum women who had not been previously studied. The geometric mean concentration of IgG4 in colostrum (3.3 micrograms/ml) was similar to the mean concentration in mature milk (3.0 micrograms/ml). The arithmetic mean for the percent of IgG = IgG4 was 10.3 +/- 3.3% for colostrum, 10.3 +/- 3.1% for mature milk, 2.6 +/- 0.3% for early plasma, and 1.7 +/- 0.3% for later plasma. Local mammary production of immunoglobulin was determined by subtracting the estimated serum contribution from the measured concentration in colostrum or milk. Evidence for local mammary production of IgG4 was found in 5 of 10 colostrum samples and 8 of 10 mature milk samples. These observations indicate that the previously observed selective enrichment of IgG4 in colostrum is also true for mature milk. These are the first studies suggesting continued local production of any immunoglobulin other than IgA in mature human breast milk.

IgD in human colostrum.

Simultaneous colostrum (C) and plasma samples (P) from 14 women, 1 to 5 days postpartum, were examined. Total IgD and specific IgD antibodies to beta-lactoglobulin, bovine serum albumin, Bermuda grass, and alpha-gliadin were measured by solid phase radioimmunoassay. The geometric mean concentrations of IgD were 35.8 (range 2.2-410) micrograms/dl for colostrum and 591.3 (range 72-4100) micrograms/dl for plasma. Six subjects had a specific IgD antibody C/P ratio more than 10-fold greater than the total IgD C/P ratio, suggesting enhancement of antibody to a specific antigen in the mammary gland. All six had C/P ratios suggestive of local enhancement of IgD antibody to Bermuda grass, and two met this criterion for enhancement of IgD antibodies to beta-lactoglobulin, bovine serum albumin, or alpha-gliadin. Specimens for these studies were obtained during the peak grass pollen season. Seventeen additional subjects were studied to compare total IgD in colostrum and plasma with total IgG and serum albumin. The mean C/P ratio for IgD (0.055 +/- 0.015) exceeded the C/P ratio for total IgG (0.015 +/- 0.003) or total albumin (0.020 +/- 0.002). For 14 of 17 subjects the colostrum/plasma ratio for IgD exceeded the C/P ratio for albumin or IgG. Data were transformed logarithmically and correlation coefficients calculated. For albumin versus IgG in colostrum, there was a strong correlation, r = 0.865, p = 0.001. This was different from albumin versus IgD, r = 0.489, p = 0.046 and from IgD versus IgG, r = 0.556, p = 0.020. These analyses support a different mechanism of entry of IgD into milk compared to IgG or albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunologic and clinical correlates of bronchial challenge responses to Bermuda grass pollen extracts.

We have studied 26 patients with asthma who had positive skin tests for Bermuda grass pollen antigen (BGP) with history, immunologic assays, and bronchial challenge with BGP. In these patients IgE anti-BGP RAST titers were higher in those with positive, 6.8 +/- 4.4% (mean +/- SEM) compared to those with negative bronchial challenges, 2.7 +/- 0.4% (p less than 0.02). Historical data did not predict bronchial challenge response. IgG4 anti-BGP RAST was not different in patients with positive and negative challenges but was markedly increased, 15.3 +/- 11.9%, in patients who had previously had BGP immunotherapy when compared to untreated patients, 3.6 +/- 5.1% (p less than 0.01). IgE anti-Bermuda grass appears to be the major contributor to susceptibility to BGP bronchial challenge. IgG4 anti-Bermuda grass is apparently unrelated to the sensitivity to challenge but appears to be a significant component of the immunologic response to immunotherapy.

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.

IgE and IgD in human colostrum and plasma.

Using radioimmunoassay techniques, we measured IgE and IgD levels in paired colostrum and plasma samples obtained within 4 days postpartum. In colostrum, IgE was detected in concentrations of 0.5-6 IU/ml in 16 out of 39 samples (41%) and less than 0.5 IU/ml in the remainder, whereas IgD was detected in all samples in concentrations of 2-2000 micrograms/dl. Only a moderate correlation was found between colostral and plasma levels of both IgE (r = +0.60) and IgD (r = +0.74). The correlation coefficient between IgE and IgD in plasma was 0.23, whereas in colostrum it was only 0.05. The colostrum:plasma ratio of IgE varied strikingly from that of IgD; the ratio of IgD was 0.1-22.2 times that of IgE. The findings argue against passive transfer of IgE and IgD from the circulation of milk and suggest possible local mammary production of either or both of these two immunoglobulins.