1. Blood Proteins and Inflammation
in the Horse
Mark V. Crisman, DVM, MSa,*,
W. Kent Scarratt, DVMa
,
Kurt L. Zimmerman, DVM, PhDb
a
Department of Large Animal Clinical Sciences, Virginia Maryland Regional
College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA
b
Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional
College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA
Inflammation is often associated with systemic alterations distant from
the initial insult that involve many organ systems all designed to eliminate
the offending antigen. Activation of the host response to infection, the
‘‘acute-phase response’’ (APR), is a highly organized physiologic reaction
that includes changes in concentrations of plasma proteins termed acute-
phase proteins (APPs). The circulating concentrations of these proteins
can provide an objective measure of the severity and extent of the underlying
condition. The APPs are increasingly being used as markers for prognosis
and monitoring response to therapy along with general determinants of
equine health. Use of APPs in veterinary medicine is becoming more wide-
spread as more commercial diagnostic kits are being validated. This article
reviews the salient features of APPs and examines their current application
and potential utility in equine inflammatory disorders.
Acute-phase proteins
A primary challenge in medicine involves the detection and monitoring of
inflammation, which results from myriad disease processes. Inflammation is
a complex process involving networks of cellular and humoral events that
are pivotal for the health and survival of all organisms. Early recognition
of systemic inflammation is essential to devise and implement an effective
treatment plan. This is especially critical if the delicate balance between
* Corresponding author.
E-mail address: farmuse@vt.edu (M.V. Crisman).
0749-0739/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.cveq.2008.03.004 vetequine.theclinics.com
Vet Clin Equine 24 (2008) 285–297

2. inflammatory and anti-inflammatory systems malfunctions, resulting in po-
tentially fatal sequelae. Inflammation that goes unrecognized or does not
display obvious clinical signs may result in subclinical infections that subse-
quently impair growth and performance. The resultant clinical deterioration
may progress to sepsis, multiple organ failure, and death. It is no surprise
that the search for early markers of inflammation has been the focus of hu-
man and veterinary medicine over the past several decades. To this end, ef-
forts have focused on biochemical identification of APPs as markers for the
degree and time course of inflammation. In response to infection or injury,
these proteins are quickly released into the bloodstream and their concentra-
tions are directly related to the severity of the underlying condition. In gen-
eral, APPs are defined as proteins whose plasma concentration increases or
decreases by at least 25% after an inflammatory stimulus [1]. Quantification
of these proteins can provide valuable diagnostic and prognostic informa-
tion and ultimately have a major influence on the outcome of the disease
process.
The APR is a nonspecific, complex, highly orchestrated inflammatory re-
sponse designed to minimize tissue damage; enhance the repair process; and
restore homeostasis after infection, trauma, or stress. This response is stim-
ulated when injured cells release arachidonic acid metabolites and products
of oxidative stress, followed by elaboration of cytokines, such as interleukin
(IL)-1b, IL-6, and tumor necrosis factor-a (TNFa), from macrophages and
monocytes. These cytokines are responsible for many of the cardinal signs of
inflammation, including pyrexia and leukocytosis. Increases in the circula-
tion of these proinflammatory mediators (especially IL-6) stimulate the he-
patic APR (at the expense of albumin synthesis) [2]. Included among the
many roles attributed to APPs are complement activation, coagulation, fi-
brinolysis, and inhibition of neutrophil proteases [1]. It is important to
note that within the complex cytokine signaling network, target cells are sel-
dom exposed to only a single cytokine. Combinations of cytokines on var-
ious target cells may have a stimulatory or suppressive effect. For example,
the elaboration of serum amyloid A (SAA) generally requires IL-6 and IL-1
or TNFa, whereas IL-1 and TNFa inhibit the induction of fibrinogen (Fb)
by IL-6. Additionally, glucocorticoids typically upregulate the stimulatory
effects of cytokines on the production of APPs, whereas insulin may play
an inhibitory role on production of some APPs [1]. Although the APR is
critical in inflammation and healing, it also functions in an ‘‘anti-inflamma-
tory’’ capacity that attenuates the inflammatory response to localized
stimuli.
Seventy five years ago, C-reactive protein (CRP) was the first APP recog-
nized in human beings, and it has subsequently become an invaluable diag-
nostic tool in human medicine to detect and monitor inflammation [3]. The
most frequently measured APPs in equine practice are Fb, SAA, and hapto-
globin (Hp) [4]. The APPs are generally classified as ‘‘positive’’ proteins, in-
cluding major or moderate, and ‘‘negative’’ proteins, depending on whether
286 CRISMAN et al

3. plasma concentrations increase or decrease in response to the challenge. The
negative APP in most species is albumin, the most abundant constituent in
plasma [5]. During the APR, albumin synthesis is downregulated in favor of
increasing hepatic synthesis of positive APPs.
The positive major APPs have the following characteristics:
Low or undetectable concentrations in plasma of healthy individuals
Concentrations increase greater than 10-fold rapidly during APR
Express a large dynamic range
Rapid decrease in concentrations with disease resolution
Relapse or secondary infection results in increased concentrations
Currently, only SAA fulfills the criteria of a positive major APP in horses.
The positive moderate APPs have the following characteristics:
Aways present in the plasma of healthy horses
Concentrations increase 1 to 10 times in response to inflammation or
injury
Response is generally slower (days to weeks) to increase, peak, and re-
turn to baseline
Examples of moderate APPs in horses include Hp, Fb, a1-acid glycopro-
tein (AGP), and CRP.
In general, a substantial increase in plasma APP concentrations in horses
has been demonstrated with viral and bacterial infections [6,7], surgery [8],
colic [9], and experimentally induced arthritis [10]. Moderate changes occur
after strenuous exercise, heatstroke, and parturition. Concentrations of the
multiple components of the APR generally increase together, although not
all increase uniformly in all horses with the same conditions. The circulating
concentration of APPs can provide an objective determinant of the health of
an animal, including the severity of any underlying condition, and allow
monitoring of the resolution of disease.
Serum amyloid A protein
Equine SAA is an acute-phase apolipoprotein that increases (O100-fold)
rapidly after tissue injury, infection, or inflammation [11]. Produced primar-
ily by hepatocytes during the APR, several extrahepatic isoforms of SAA,
specifically SAA3, have been identified in horses [10,12,13]. Extrahepatic se-
cretion of SAA3 has been demonstrated in the mammary gland (colostrum)
and joints (synovial fluid) from horses [13,14]. The physiologic roles of SAA
are not completely understood, because various effects have been reported.
These include enhancement or inhibition of leukocyte functions, chemotac-
tic recruitment of inflammatory cells to the site of infection [15], inhibition
of lymphocyte and endothelial cell proliferation, inhibition of platelet aggre-
gation, and phagocytosis. SAA may also inhibit myeloperoxidase release
and directed migration of phagocytes and modulate connective tissue
287BLOOD PROTEINS AND INFLAMMATION IN THE HORSE

4. breakdown in normal remodeling. Extrahepatic production of SAA3, al-
though speculative, suggests a ‘‘housekeeping’’ role for the protein by pro-
viding an immediate defense against tissue injury from inflammatory
challenges. Mammary-associated SAA3 may provide a beneficial function
for the suckling neonate or maintenance of the mammary gland [13]. Alter-
natively, SAA is the primary precursor of amyloid A and has been impli-
cated in the pathogenesis of amyloidosis [16].
Reference intervals for plasma SAA concentrations in healthy horses
have been reported to range from less than 0.5 to 20 mg/L [7,14,17]. The
low constitutive expression of SAA in healthy horses allows straightforward
interpretation of even moderate increases in SAA concentrations after an in-
flammatory stimulus. The short half-life of SAA allows accurate monitoring
of disease after therapeutic intervention. Therefore, sequential SAA deter-
minations may be potentially useful in patient management and prognosti-
cation. The overall diagnostic sensitivity and kinetic profile of SAA
(compared with moderate APPs, such as Fb) make it an ideal marker of in-
flammation and tissue damage.
Clinical applications of serum amyloid A
Several studies have evaluated the application and efficacy of SAA in
healthy and septic neonates [6,17,18]. Neonatal septicemia is one of the
most challenging problems encountered by equine veterinarians; thus, rapid
diagnosis and aggressive therapy have a major influence on outcome. Typ-
ically, sepsis refers to disseminated gram-negative bacterial infections.
Gram-positive bacterial and viral infections, trauma, hypovolemia, and
hemorrhage may all activate the proinflammatory pathways, however, re-
sulting in the systemic inflammatory response syndrome (SIRS) [19]. Inves-
tigations have suggested that SAA is a sensitive indicator of inflammation
and may be beneficial in differentiating neonatal weakness, diarrhea, and
septicemia. Increased SAA concentrations have been reported in foals
with various bacterial infections [18], septicemia, localized infections (in-
cluding omphalophlebitis), and arthritis [17]. Higher SAA concentrations
have been noted with bacterial infections, whereas viral infections elicit
a more tempered response [7]. In contrast, noninfectious causes of neonatal
weakness (failure of passive transfer, pre- and dysmaturity, maladjustment
syndrome, and meconium impaction) have been associated with normal
[17,18] to slightly increased SAA concentrations [20]. This may be attribut-
able to assay variability and sampling technique. Nonetheless, it is generally
agreed that SAA determinations proved superior when compared with clas-
sic markers of inflammation (eg, Fb, leukocyte counts) in distinguishing in-
fectious from noninfectious causes of SIRS.
Concentrations of SAA in equine respiratory disease have also been
evaluated, specifically equine influenza and Rhodococcus equi pneumonia.
A study on equine influenza indicated that SAA concentrations increased
288 CRISMAN et al

5. during the first 48 hours of clinical signs and then returned to baseline over the
ensuing 11 to 22 days in uncomplicated cases [7]. SAA determinations proved
to be a more sensitive indicator of infection than nasal swabs and correlated
well with disease resolution. A recent study by Cohen and colleagues [6] eval-
uated SAA concentration in foals with R equi pneumonia and its utility to dif-
ferentiate normal from affected foals. Results indicated that bimonthly SAA
determinations in foals less than 1 month of age were not a useful screening
tool for R equi infection. This may have been attributable to the nature of the
disease (insidious with walled off pulmonary abscesses) or the long sampling
interval. Regardless, more research is needed in this area to determine conclu-
sively the usefulness of SAA in foals with R equi pneumonia.
Concentrations of SAA have been determined in horses with colic result-
ing from inflammatory and noninflammatory causes. Horses with colic
attributable to inflammatory causes (enteritis, peritonitis, colitis, or abdom-
inal abscesses) had significantly higher concentrations of SAA than horses
with noninflammatory causes (displacement or obstruction). Additionally,
SAA concentrations were higher in horses that failed to survive the colic ep-
isode compared with survivors; however, the difference was not substantial
enough to be clinically useful at this time [9].
Studies of SAA response to equine joint disease have been recently per-
formed on serum and synovial fluid [21]. SAA concentrations in serum and sy-
novial fluid were lower than assay detection limits in healthy horses. Synovial
fluid and serum SAA concentrations were significantly elevated in horses with
suspected infectious arthritis and tenovaginitis, suggesting that SAA may be
a useful biologic marker for horses with joint disease. This study corroborated
an earlier project using an experimentally (lipopolysaccharide) induced arthri-
tis, in which increases in synovial fluid SAA reflected inflammatory activity
and concentrations decreased during stages of clinical improvement [10].
Recently, an excellent review of equine SAA was published detailing
many of the salient features associated with APPs [22].
Analysis of serum amyloid A
Previously, SAA measurements were primarily the domain of research
laboratories. Several methodologies have been used for determining equine
SAA, including ELISA [11], slide-reversed passive latex agglutination [23],
and latex agglutination immunoturbidimetric assay [17]. A commercially de-
veloped immunoturbidimetric assay for human SAA (LZ test SAA, EIKEN
LZ-serum amyloid A assay, Mast Group, Merseyside, United Kingdom) has
recently been evaluated for use in horses [14]. This rapid automated assay
demonstrated good precision and is appropriate for determining equine
SAA. A system has been developed in Europe to allow small diagnostic lab-
oratories to measure equine SAA in 30 minutes (Equinostic, DN, EVA,
Equibnostic, Copenhagen, Denmark). According to company literature,
this equine SAA test is rapid and precise.
289BLOOD PROTEINS AND INFLAMMATION IN THE HORSE

6. Haptoglobin
Hp is classified as a moderate APP, demonstrating an increase of 1 to
10 times greater than the reference interval in horses during the APR (ref-
erence interval: 2–10 g/L). Hp is classified as a major APP in ruminants
and has been proved to be an effective marker for the presence and sever-
ity of such diseases as mastitis, pneumonia, and endocarditis in cattle [24].
Produced primarily by hepatocytes, Hp is an a2-globulin that primarily
functions to prevent the loss of iron by the formation of stable complexes
with free hemoglobin (Hb) in the blood. Hp synthesis is stimulated by the
Hb concentration in plasma, and the resultant Hp-Hb complex provides
an efficient means for collection of free Hb, which prevents external
leak or loss of iron and ameliorates the oxidative damage to tissues asso-
ciated with free Hb (from hemolysis). Additionally, the Hp-Hb complexes
are large enough to reduce renal filtration of free Hb and iron substan-
tially from plasma. These complexes are removed by hepatocytes, allowing
reutilization of iron and amino acids. Although several functions have
been ascribed to Hp, it is believed to have a bacteriostatic effect by lim-
iting the availability of iron, which is essential for bacterial growth. Hp
may also have anti-inflammatory actions by protecting against reactive
oxygen species and inhibiting granulocyte chemotaxis and phagocytosis
[24]. Hp is also reported to aid in wound repair by stimulating angiogen-
esis [25].
Clinical application of haptoglobin
As an APP, Hp concentrations increase during any inflammatory process
(eg, infection, stress, trauma, allergy). Increased serum Hp concentrations in
horses have been observed after surgery [26], noninfectious arthritis [4], and
carbohydrate-induced laminitis [27]. Horses with colic did not demonstrate
an increase in Hp concentrations [28]. Serum concentrations of Hp can be
influenced by factors other than the APR, however. Increased concentra-
tions of free Hb in serum (ie, acute hemolytic event) are followed by a sub-
stantial decline in concentration of free Hp, because it is quickly consumed
during such hemolytic syndromes. Therefore, serum Hp concentration may
be a sensitive indicator of intra- or extravascular hemolysis and infection or
inflammation in horses [26,29].
Analysis of haptoglobin
Currently, techniques used to determine equine Hp concentrations are
fairly laborious and generally restricted to research laboratories. Techniques
include single radial immunodiffusion (SRID) [30], serum protein electro-
phoresis (SPE; increased a2-globulin fraction) [31], Hb-Hp binding capacity
assay [4], and immunoturbidimetry [32]. A method for estimation of serum
Hp using capillary zone electrophoresis has also been described [33].
290 CRISMAN et al

7. Fibrinogen
Fb was one of the earliest recognized APPs. Fb, a soluble plasma glyco-
protein synthesized by the liver, is considered a moderate APP with concen-
trations increasing 1- to 10-fold over 24 to 72 hours after the induction of
inflammation. The relatively wide reference interval for Fb concentrations
in healthy horses (200–400 mg/dL, 2–4 g/L) and lengthy response period af-
ter an inflammatory stimulus have rendered Fb a fairly insensitive APP. Sev-
eral functions have been ascribed to Fb, including providing a substrate for
fibrin formation in tissue repair and providing a matrix for migration of in-
flammatory-related cells. Fb binds to cell surface integrins (CD11/CD18) of
phagocytes, initiating a cascade of intracellular signals promoting the en-
hancement of degranulation, phagocytosis, and antibody-dependent cyto-
toxicity. Over the past several decades, Fb has been used to diagnose and
monitor various inflammatory conditions in horses. A recent study evaluat-
ing serum iron and plasma Fb concentrations in systemic inflammatory dis-
eases in horses concluded that an increase in Fb concentration was
associated with a poor prognosis. Hypoferremia was a more accurate reflec-
tion of acute, subacute, and chronic inflammation in sick horses older than
2 months of age, however [34]. Plasma Fb concentrations have been used to
detect and monitor R equi pneumonia in foals. Measurement of Fb concen-
trations and leukocyte counts proved useful for early identification of
R equi–infected foals, although leukocyte counts proved superior under field
conditions [35]. Another study evaluated SAA and Fb concentrations in
healthy horses experimentally infected with Streptococcus zooepidemicus
and monitored the progression of pneumonia. Results indicated that SAA
responded more rapidly than Fb to changes in clinical signs of pneumonia
[36]. Together, these studies suggest that an alteration in Fb concentration
is not necessarily in agreement with actual disease detection or progression.
Although determination of plasma Fb concentration has long been used for
detecting inflammatory diseases in horses, its relatively slow APR after an
inflammatory insult seriously hampers its clinical utility. Nevertheless, Fb
measurements are relatively easy and inexpensive, and this fact has likely se-
cured its continued wide use in veterinary medicine.
Analysis of fibrinogen
A heat precipitation method is used as a quick estimate of Fb concentration
[37]. More accurate methods include modifications of the Ratnoff-
Menzie assay, measurement of clot weight, and quantification of immunopre-
cipitate formed with specific anti-Fb antiserum.
a1-acid glycoprotein
AGP is a highly glycosylated protein synthesized and secreted primarily
by hepatocytes. It is considered a moderate APP in most species and is
291BLOOD PROTEINS AND INFLAMMATION IN THE HORSE

8. more likely to be associated with chronic conditions rather than acute in-
flammation. Local (extrahepatic) AGP production has been confirmed
and is believed to contribute to the general maintenance of homeostasis
by reducing tissue damage associated with inflammation, particularly in ep-
ithelial and endothelial cells [38]. Two major functions have been attributed
to AGP, namely, drug binding and immunomodulation. Similar to albumin,
AGP is capable of binding to endogenous or exogenous substances, such as
heparin, histamine, serotonin, and steroids [38]. This critical function may
keep total drug-binding levels constant during the APR, whereas albumin,
a negative APP, decreases in total concentration. AGP has been reported
to inhibit neutrophil activation, increase secretion of IL-1 receptor antago-
nist by macrophages, and enhance clearance of lipopolysaccharide by di-
rectly binding and neutralizing the latter [38,39].
Although AGP has been proved to be a useful APP in other species, in-
cluding pigs [40] and cattle [41,42], little work has been done in horses. One
study reported increased concentrations of AGP (as determined by SRID)
in colts 2 to 3 days after castration and in adult horses after jejunojejunos-
tomy and return to baseline values 14 to 28 days later [43]. Another study
evaluating a carbohydrate overload model of laminitis in ponies reported in-
creased concentrations of AGP 4 hours after administration of carbohy-
drate (24 hours before the onset of clinical lameness) [27].
C-reactive protein
CRP has been well documented as an APP in human beings, ruminants,
dogs, and, to a lesser degree, horses [1,24]. It is considered to be a moderate
APP in horses, with a two- to threefold increase over several days. CRP has
several proinflammatory effects, including activation of the complement cas-
cade, induction of inflammatory cytokines, and phagocytosis. CRP also has
significant anti-inflammatory effects, such as inhibiting chemotaxis and the
generation of superoxide by neutrophils and preventing the adhesion of neu-
trophils to endothelial cells. Studies conducted in the early 1990s suggested
that high CRP concentrations occurred in horses with pneumonia, enteritis,
and arthritis [44].
Serum protein electrophoresis
Serum proteins consist of albumin and globulins, which usually are quan-
titated on a standard biochemical profile. In contrast to albumin, which is
a single type of protein, globulins are a mixture of proteins that tend to mi-
grate in groups on SPE [31]. These groups are known as a-globulins, b-glob-
ulins, and g-globulins. The first step to investigate an increase or decrease in
total serum globulins, as noted on the biochemical profile, is to perform SPE
[31]. SPE is the current standard method for the fractionation of serum
292 CRISMAN et al

9. proteins, and the results can be a useful diagnostic aid to the clinician. There
are, however, only a few diseases for which the pattern of SPE is pathogno-
monic [31].
The principle of the electrophoretic separation of serum proteins is based
on the migration of charged proteins in an electric field [31]. The direction
and rate of migration of a protein are based on the type of charge (anion
or cation) and size of the protein. A ‘‘normal’’ equine SPE consists of six
fractions, including albumin, a1-globulin, a2-globulin, b1-globulin, b2-glob-
ulin, and g-globulin.
The electrophoretogram is stained, and a densitometer is used to deter-
mine the proportion of proteins in these fractions, which are then used in
conjunction with the total serum protein concentration to determine specific
concentrations of the fractions. Reference values for these fractions on SPE
of the adult horse are albumin (26–37 g/L), a1-globulin (0.6–7 g/L), a2-glob-
ulin (3–13 g/L), b1-globulin (4–16 g/L), b2-globulin (3–9 g/L), g-globulin
(6–19 g/L), and total serum protein (52–79 g/L) [31].
Albumin is the most prominent of the normal serum proteins on SPE and
constitutes approximately 50% of the total serum protein [31]. The albumin
fraction migrates closest to the anode and is the most homogeneous fraction
on SPE [31,45]. Equine serum often has a minor postalbumin fraction,
which appears as a shoulder on the cathodal side of the albumin peak.
This shoulder often becomes more prominent with hypoalbuminemia [31].
The a-globulin fraction is the most rapidly migrating fraction of the glob-
ulins and migrates as a1- (fast) and a2- (slow) globulin fractions [31]. The a1-
and a2-globulin fractions are identified as the first two peaks after albumin
on SPE. Important a1- and a2-globulins include antitrypsin, high-density li-
poprotein, very-low-density lipoprotein, macroglobulin, ceruloplasmin, and
Hp [31].
The b-globulin fraction trails the a-globulin fraction on SPE and mi-
grates as b1- (fast) and b2- (slow) globulin fractions [31]. The b1- and b2-
globulin fractions are identified as the third and fourth peaks after albumin
on SPE. Important b-globulins include complement (C3, C4), transferrin,
ferritin, and CRP. Some of the immunoglobulins (IgM and IgA) can mi-
grate in the b-globulin region [31].
The g-globulin fraction trails the b-globulin fraction on SPE and includes
IgG, IgA, IgM, and IgG subclass T (IgG [T]). The concentrations of these
immunoglobulins in horses have also been quantitated by SRID [46].
Interpretation of serum protein electrophoresis
The profile of SPE and the absolute values of the individual fractions oc-
casionally can be used to make a diagnosis but are often used to direct ad-
ditional diagnostic tests. The profile of SPE in an individual animal is
relatively constant but may be influenced by age, hormones, pregnancy,
and lactation [31]. A deficiency of dietary protein, hypothermia,
293BLOOD PROTEINS AND INFLAMMATION IN THE HORSE

10. hyperthermia, and inflammation also can influence the profile of SPE [31].
Common abnormalities identified on SPE include hypoalbuminemia, hyper-
globulinemia, and hypoglobulinemia.
Hypoalbuminemia is caused by a decreased synthesis or an increased loss
of albumin. Albumin is synthesized in the liver, and hypoalbuminemia is
a feature of chronic diffuse liver disease [31,45]. A prominent postalbumin
fraction on SPE, with or without hypoalbuminemia, has been considered
pathognomonic for liver disease in the horse. An increased loss of albumin
may be caused by renal or gastrointestinal disease and accumulation within
the thoracic or abdominal cavity [31,45].
Hyperglobulinemia is caused by an increase in the a-, b-, or g-globulin
fractions and occurs in a variety of disorders. An increase in the a-globulin
fraction occurs in acute inflammatory disorders, because the APPs, includ-
ing SAA and macroglobulin, migrate in the a-globulin fraction [31]. An in-
crease in the b-globulin fraction occurs in active liver disease, because
transferrin and IgM migrate in the b-globulin fraction [31]. An increase in
the beta and gamma globulin fractions (beta-gamma bridging) on SPE is
noted when there is no clear separation between the beta-2 and gamma glob-
ulin fractions. Beta-gamma bridging may be caused by an increase in IgM or
IgA, chronic active hepatitis, or lymphosarcoma [31,45]. Experimental infec-
tions of the intestinal tract with Strongylus vulgaris larvae have been asso-
ciated with an increased concentration of IgG (T) [47,48].
Hypergammaglobulinemia may be caused by a broad increase (poly-
clonal gammopathy) or a sharp increase (monoclonal gammopathy) in
gamma globulins. The broad increase in gamma globulins that characterizes
a polyclonal gammopathy is caused by the heterogeneity of clones of plasma
cells, which produce a heterogeneous mix of immunoglobulins. Any or all of
the immunoglobulin groups can be increased. A polyclonal gammopathy
often is associated with a chronic inflammatory disease, such as hepatitis,
pleuropneumonia, immune-mediated disease, neoplasia, or a chronic suppu-
rative disorder [31,45].
A monoclonal gammopathy is characterized by a sharp increase (or
spike) in one of the immunoglobulins. The monoclonal spike is caused
by a single clone of plasma cells that produces a single class of immuno-
globulin or an immunoglobulin fragment (referred to as a paraprotein, M
protein, or M component), which can be identified by the results of
electrophoresis, immunoelectrophoresis, or immunodiffusion [31,49,50].
Monoclonal gammopathy occurs infrequently in the horse and has been
associated with plasma cell myeloma [49], malignant lymphoma [51] and
idiopathic causes [52].
The diagnostic and prognostic value of SPE in horses with chronic diar-
rhea was reported [49]. Horses with larval cyathostomiasis had significantly
higher levels of beta-1 globulin. A normal concentration of beta-1 globulin
was not a reliable indicator of the absence of larval cyathostomiasis, how-
ever. Horses with chronic diarrhea that did not survive were more likely
294 CRISMAN et al

11. to have a lower concentration of albumin and a higher concentration of
alpha-2 globulin [53].
Hypoglobulinemia may be caused by a reduction in the alpha, beta, or
gamma globulin fractions and occurs in a variety of disorders. Failure of
passive transfer of immunity in foals is associated with a deficiency of
gamma globulin. A horse with a protein-losing gastroenteropathy often
has hypoglobulinemia and hypoalbuminemia.
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