Immunoglobulin Content of Colostrum

The immunoglobulins account for approxi­mately 40% of the total protein in colostrum. Data from studies in ruminants indicate that colostral immunoglobulins are derived from the serum with little, if any, local synthesis/¹ It is reasonable to assume that equine colostral immunoglobulins also originate in the serum, especially in view of the similarity between mare serum and colostrum.

The major immunoglobulin in colostrum is IgG;⁴⁰ IgM, IgA and IgG(T) are also present.³⁶ The IgG level in the colostrum of approxi­mately 10% of Thoroughbred mares was defi­cient and correlated with low levels of serum IgG in foals that suckled.⁴² The deficiency of co­lostral IgG could not be explained by either low

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IgG levels in maternal serum or by prepartu-rient depletion of colostrum from dripping.

Absorption of Maternal Antibodies

The absorption of maternal antibodies and other colostral proteins occurs in the small in­testine of newborn foals via pinocytosis by vil-lus epithelial cells. Protein globules are transported through the cells, extruded into the tissue spaces of the lamina propria, and transported into the circulation by lymph.⁴¹ Antibodies appear in the blood within a few hours after the ingestion of colostrum.⁴³ The absorption of macromolecules is apparently not selective in newborn foals⁴¹ The intestinal absorption of protein is highest at birth and de­creases thereafter until closure by 24 hours of age.^44-45 This rapid closure is caused by the rapid turnover of intestinal epithelial cells in­volved in absorption and replacement by more mature cells that do not absorb proteins. This decreasing ability to absorb maternal antibod­ies until 24 hours of age is an important con­sideration in the treatment of foals with failure of passive transfer.

By 48 hours of age, levels of serum immu-noglobulins in normal foals are near those in maternal serum. There is considerable varia­tion in the amount of IgG absorbed, depending on the amount of colostrum ingested and the amount of IgG in colostrum. In one study, the mean colostral IgG level in 32 mares was 2354 mg/dl, with a range of 1080-8960 mg/dl.⁴² The variation in intestinal absorption in some foals receiving adequate amounts of colostral IgG may be related to several factors, including stress.⁴³

Failure of Transfer of Maternal Antibodies

The significance of passive transfer of mater­nal antibodies in colostrum is well docu­mented. Obtaining maternal antibodies in colostrum is the most important consideration for the newborn foal, after the consideration of food.

Incidence: In a study of 43 Arabian and 4 Thoroughbred foals from several different lo­cations, 20% had less IgG than 200 mg/dl serum at 48 hours of age.⁴⁸ Of 9 affected foals, 3 failed to nurse properly and 2 of these 3 sub­sequently died of infections. The remaining 6 foals nursed normally but still failed to obtain normal amounts of maternal antibodies; 5 of these had nonfatal respiratory infections at 2-5 weeks of age.

IgG levels in maternal serum or by prepartu-rient depletion of colostrum from dripping.

Absorption of Maternal Antibodies

The absorption of maternal antibodies and other colostral proteins occurs in the small in­testine of newborn foals via pinocytosis by vil-lus epithelial cells. Protein globules are transported through the cells, extruded into the tissue spaces of the lamina propria, and transported into the circulation by lymph.⁴¹ Antibodies appear in the blood within a few hours after the ingestion of colostrum.⁴³ The absorption of macromolecules is apparently not selective in newborn foals⁴¹ The intestinal absorption of protein is highest at birth and de­creases thereafter until closure by 24 hours of age.^44-45 This rapid closure is caused by the rapid turnover of intestinal epithelial cells in­volved in absorption and replacement by more mature cells that do not absorb proteins. This decreasing ability to absorb maternal antibod­ies until 24 hours of age is an important con­sideration in the treatment of foals with failure of passive transfer.

By 48 hours of age, levels of serum immu-noglobulins in normal foals are near those in maternal serum. There is considerable varia­tion in the amount of IgG absorbed, depending on the amount of colostrum ingested and the amount of IgG in colostrum. In one study, the mean colostral IgG level in 32 mares was 2354 mg/dl, with a range of 1080-8960 mg/dl.⁴² The variation in intestinal absorption in some foals receiving adequate amounts of colostral IgG may be related to several factors, including stress.⁴³

Failure of Transfer of Maternal Antibodies

The significance of passive transfer of mater­nal antibodies in colostrum is well docu­mented. Obtaining maternal antibodies in colostrum is the most important consideration for the newborn foal, after the consideration of food.

Incidence: In a study of 43 Arabian and 4 Thoroughbred foals from several different lo­cations, 20% had less IgG than 200 mg/dl serum at 48 hours of age.⁴⁸ Of 9 affected foals, 3 failed to nurse properly and 2 of these 3 sub­sequently died of infections. The remaining 6 foals nursed normally but still failed to obtain normal amounts of maternal antibodies; 5 of these had nonfatal respiratory infections at 2-5 weeks of age.

In a study of 87 foals on 2 Thoroughbred breeding farms, 10% of foals had a failure in passive transfer (IgG<200 mg/dl) and 14% had a partial failure (IgG 200-400 mg/dl).⁴² Of 21 affected foals, only 1 failed to nurse properly. Among the 9 foals with failure of passive trans­fer, 7 had infections; among the 12 partial fail­ures, 3 had infections. All unaffected foals had serum IgG levels of more than 400 mg/dl and none had an infection requiring treatment. This indicates that the more maternal anti­body absorbed by the foal, the better. However, some transfer is better than none.

More information is needed from various parts of the country and from a variety of man­agement conditions to determine the incidence of failure of transfer of maternal antibodies. Even with additional data, the incidence of failures (IgG<200 mg/dl) will probably be 5-10%. Such a high incidence cannot be ignored by those providing veterinary care to foals.

Causes: Foals too weak to nurse or those par­tially rejected by the mare have no access to colostrum. Weak foals include those born with neonatal infections, such as viral rhinopneu-monitis, and those injured at or after birth.

It is commonly thought that lactation prior to parturition lowers colostral immunoglobu-lin levels.⁴³ However, this theory requires doc­umentation. There was no evidence of pre­mature lactation in case reports of colostral im-munoglobulin deficiency.⁴²'⁴⁹ In the limited sample studied, about 10% of the mares had colostrum deficient to some extent in IgG.⁴² The cause for this deficiency is not known and fur­ther investigations are needed. The low level of colostral IgG explained some failures and partial failures in passive transfer.

It has been postulated that mares foaling be­fore 320 days may not produce colostrum and any colostrum produced contains low levels of immunoglobulins.⁴³ Prematurity should not af­fect the ability of the foal to absorb immuno-globulin since the specialized epithelial cells necessary for absorption are present relatively early in gestation,

About 3-4% of all foals do not absorb immu-noglobulin even though they nurse normally and the colostrum contains adequate levels of immunoglobulin.⁴²⁴⁸'¹⁹ These cases account for about 30% of failures of passive transfer. In other species, corticosteroids cause changes in permeability of small intestinal epithelial cells and interfere with uptake of macromolecules.⁴¹ It is not known if this is a factor in foals that do not absorb colostral immunoglobulins.

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Diagnosis: Several methods of immunoglob-ulin concentration measurement have been de­scribed. Radial immunodiffusion for IgG is specific and allows good assessment of transfer of maternal antibodies. Serum electrophoresis, coupled with measurement of total serum pro­tein, provides values from which total serum gamma globulin can be calculated and passive transfer evaluated. Turbidity detected in the zinc sulfate turbidity test indicates absorption of immunoglobulins at a level of 400-500 mg/ dl serum.²⁵ Quantitative zinc sulfate turbidity tests can also be performed.

Criteria for transfer of maternal antibodies are foal serum IgG levels less than 200 mg/dl as determined by single radial immunodiffu­sion, or serum gamma-globulin levels less than 200 mg/dl serum as determined by serum elec­trophoresis and total serum protein measure­ments. Partial failure is indicated by foal serum IgG or gamma-globulin levels of 200-400 mg/dl serum. A lack of turbidity in the qualitative zinc sulfate turbidity test indicates failure or partial failure of passive transfer.

Treatment: Foals that fail to nurse for a va­riety of reasons are treated by feeding frozen colostrum after thawing. Colostrum must be fed as soon as possible after birth since the ab­sorption rate declines from 100% at. birth to zero by 24 hours."⁹ A total of 3 L colostrum, di­vided into 3 or 4 doses fed at hourly intervals, should be given beginning as soon as possible after birth. In the absence of colostrum, adult equine serum or plasma may be fed. However, 6-9 L serum or plasma should be fed because serum and plasma have lower IgG levels than does colostrum and they lack colostral factors that enhance absorption.⁴¹

In foals older than 15-24 hours, plasma transfusions are the most reasonable form of therapy. The plasma donor should be a stallion or gelding from a local stable to minimize the possibility of neonatal isoery thro lysis and to maximize the probability of having antibodies to indigenous pathogens. Plasma should be tested with hemagglutination and hemolytic tests for antibodies to the recipient foal's RBC.⁵⁰

If a large amount of colostrum or plasma is to be frozen, a small aliquot could be sent to the Veterinary Serology Laboratory of the Univer­sity of California at Davis for screening against a panel of equine RBC types to eliminate the need for further testing.²⁵

To collect plasma, blood should be obtained aseptically in sterile bottles, using heparin or sodium citrate as an anticoagulant. The RBC should be allowed to settle to the bottom of the bottle for about an hour, after which the plasma is decanted and centrifuged to remove the remaining RBC. Bacterial contamination should be avoided as bacterial pyrogens cause hyperventilation, trembling and temporary muscular weakness in recipients.⁴¹*⁹

The proper amount of plasma to administer is not known, especially in foals with only a partial failure of passive transfer. This is es­pecially true considering that the level of an­tibody to a specific pathogen is more important than the total IgG level. In children with agammaglobulinemia, infusion of 20 ml plasma/ kg body weight resulted in serum IgG levels of about 300 mg/dl.⁵¹ Infusion of 20 ml plasma/kg body weight resulted in serum IgG levels of 500 mg/dl in recipient foals.²⁵ These results, com­bined with knowledge of the recipient foal's serum IgG level, provide enough information to estimate a suitable dose.

Effects of Colostral Antibodies

The levels of colostral total protein and im-munoglobulin decrease dramatically as pro­duction of colostrum is curtailed. By 9-24 hours postpartum, the IgG content of colostrum is less than 10% of prepartum levels.⁵² The pre­dominant immunoglobulin changes from IgG in colostrum to IgA in milk.⁵³ The IgA in milk may protect foals against enteric infection.

Maternal antibodies in colostrum are not al­ways protective, as in the case of neonatal isoerythrolysis.⁵⁰ In this disease, colostral antibodies react with the foal's RBC to cause hemolysis, anemia and possibly death. Colos­trum from mares with serum antibodies to the stud's RBC or colostrum containing antibodies to the newborn foal's RBC should not be fed. Such foals should be treated as described for foals failing to nurse. Foals that have nursed and show signs of isoerythrolysis should be re­moved from the mare until 36-48 hours after birth. If 36-48 hours have elapsed since birth, no useful purpose is served by stopping the foal from nursing since absorption of antibodies from the gut has ceased.

The ability of maternal antibodies to sup­press the induction of an immune response to vaccination is well recognized in human and veterinary medicine. Mechanisms of suppress­ing the immune response involve antigen masking and possibly a central effect. One practical problem with this suppression in­volves the proper timing of vaccination when foals absorb colostral antibodies to antigens in

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the vaccine.⁵⁴ The ability to block immuniza­tion depends on the amount of antibody pres­ent, which is determined by the amount absorbed from colostrum and the time elapsed after absorption.

Maternal antibodies are catabolized from foal serum at varying rates, depending on the class of immunoglobulin. For example, IgM is cleared from foal serum 5 times faster than IgG.^33..⁵⁵ For this reason, initial vaccinations are not given until about 2 months of age. Even then, the injection is usually repeated to boost the response.

Serum from foals that have absorbed normal amounts of colostral immunoglobulins con­tains antibody levels similar to those in the mare. These absorbed antibodies must be con­sidered in evaluation of serologic results. For instance, foals from mares seropositive to equine infectious anemia (EIA) virus absorb EIA an­tibodies from colostrum. Some of these foals are infected with EIA virus and remain sero­positive for life.^56..⁵⁷ The remaining uninfected foals are seropositive after nursing but become seronegative by 65-182 days of age.⁵⁷ There­fore, regulations for the testing of foals for EIA take this clearance time into account, as do interpretations of foal antibody titers to other microorganisms.