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Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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148<br />

Chapter | 5 Proteins, Proteomics, and the Dysproteinemias<br />

Lymphomas can elicit either a polyclonal or monoclonal<br />

hyperglobulinemia . The hyperglobulinemic peaks can<br />

occur anywhere between the β 1 and γ 2 regions and range<br />

from very broad, diffuse peaks to very sharp, monoclonal<br />

spikes. The polyclonal peaks <strong>of</strong> lymphoma are thought<br />

to be the result <strong>of</strong> a tumorous group <strong>of</strong> distantly related<br />

clones in contrast to the single discrete clones, which give<br />

rise to the monoclonal spikes.<br />

v . Increased γ -Globulin (Sharp Increases): Monoclonal<br />

Gammopathy The monoclonal forms are characterized<br />

by sharp spikes <strong>of</strong> immunoglobulin. They may occur<br />

in the β region, but are frequently limited to the γ<br />

region ( Fig. 5-9d ). A useful guideline for interpretation<br />

is to compare visually the sharpness <strong>of</strong> these spikes<br />

to the albumin peak. One or the other slope <strong>of</strong> the<br />

monoclonal spike is as steep or steeper than one <strong>of</strong> the<br />

slopes <strong>of</strong> the albumin peak. The monoclonal spike is<br />

the result <strong>of</strong> a single clone producing a single class <strong>of</strong><br />

immunoglobulin usually abnormal in nature. Thus, the<br />

monoclonal immunoglobulins are <strong>of</strong> identical structure<br />

and move as one on the SPE. These immunoglobulins<br />

have been described as “ paraproteins. ” The characteristic<br />

monoclonal spike in the γ region, Bence-Jones proteinuria,<br />

and plasma cell tumors have been general findings in<br />

multiple myelomas reported in the horse ( Geelen et al. ,<br />

1997 ; Pusterla et al. , 2004 ), dog ( Giraudel et al. , 2002 ),<br />

and cat ( Farrow and Penny, 1971 ; Patel et al. , 2005 ). Lightchain<br />

disease with Bence-Jones proteins in the plasma and<br />

urine has been observed in dogs ( Hurvitz et al. , 1971 ).<br />

Lymphomas may present with monoclonal spikes<br />

depending on the degree <strong>of</strong> cloning <strong>of</strong> the tumor cells.<br />

The dominant monoclonal protein was identified as IgM<br />

in a case <strong>of</strong> lymphocytic leukemia in a dog ( Braund et al. ,<br />

1978 ). A biclonal gammopathy has been observed in a<br />

dog with a combined myeloma and cutaneous lymphoma<br />

( Jacobs et al. , 1986 ).<br />

A retrospective study <strong>of</strong> 18 cases <strong>of</strong> monoclonal gammopathies<br />

in the dog confirmed that most were associated<br />

with lymphoproliferative tumors, including multiple myelomas,<br />

Waldenström’s macroglobulinemia, lymphoma, chronic<br />

lymphocytic leukemia, and mucocutaneous plasmacytoma<br />

(Giraudel et al. , 2002 ). However, nonmyelomatous monoclonal<br />

gammopathies were identified in cases <strong>of</strong> leishmaniasis<br />

and ehrlichiosis in this and other studies ( Breitschwerdt<br />

et al. , 1987 ). Monoclonal gammopathies have also been<br />

reported in canine amyloidosis ( Schwartzman, 1984 ).<br />

Generally, the clinical characteristics <strong>of</strong> the monoclonal<br />

gammopathies are referable to the magnitude <strong>of</strong> lymphocyte<br />

or plasma cell proliferation, the extent <strong>of</strong> organ<br />

infiltration, and production <strong>of</strong> abnormal protein. Thus,<br />

immunologically associated diseases tend to be multifaceted<br />

and can present with bleeding tendencies, glomerulonephritis,<br />

polyarthritis, arteritis, hepatitis, and SLE. All<br />

monoclonal gammopathies are not necessarily pathological,<br />

however, because they can be benign. Consequently, care<br />

must be exercised in the final evaluation <strong>of</strong> a monoclonal<br />

gammopathy.<br />

3 . Increased A:G—Abnormal Pr<strong>of</strong>i le<br />

a . Increased Albumin<br />

True overproduction <strong>of</strong> albumin does not occur in any animal.<br />

Therefore, any rise in albumin is only a relative hyperalbuminemia<br />

because <strong>of</strong> hemoconcentration as a result <strong>of</strong><br />

water loss and dehydration.<br />

b . Decreased Globulins<br />

The absence <strong>of</strong> γ -globulins in fetal serum or in serum<br />

from precolostral or colostrum-deprived neonatal animals<br />

( Weaver et al. , 2000 ) can be readily demonstrated on SPE<br />

(see Fig. 5-8 ). Hypo- γ -globulinemia occurred in about<br />

15% <strong>of</strong> foals less than 2 weeks <strong>of</strong> age and was attributed<br />

to failure <strong>of</strong> colostral transfer even though most had nursed<br />

( Mcguire et al. , 1975a ; Sellon, 2000 ). Combined immunodeficiency<br />

<strong>of</strong> Arabian foals is thought to be an inherited<br />

autosomal recessive disease. The disease is characterized<br />

by lymphopenia, failure to synthesize IgG, IgM, and IgA<br />

and early death ( Davis and Jones, 2003 ; Mcguire et al. ,<br />

1975b ; Perryman, 2000 ). A selective IgM deficiency has<br />

been reported ( Perryman et al. , 1977 ).<br />

REFERENCES<br />

Abate , O. , Zanatta , R. , Malisano , T. , and Dotta , U. ( 2000 ). Canine serum<br />

protein patterns using high-resolution electrophoresis (HRE) . Vet. J.<br />

159 , 154 – 160 .<br />

Alberts , B. , Johnson , A. , Lewis , J. , Raff , M. , Roberts , K. , and Walter , P.<br />

( 2002 ). “ Molecular Biology <strong>of</strong> the Cell .” Garland , New York .<br />

Allison , A. C. ( 1960 ). Turnovers <strong>of</strong> erythrocytes and plasma proteins in<br />

mammals . Nature 188 , 37 – 40 .<br />

Alsemgeest , S. P. M. , Taverne , M. A. M. , Boosman , R. , Vanderweyden ,<br />

B. C. , and Gruys , E. ( 1993 ). Peripartum acute-phase protein serum<br />

amyloid-A concentration in plasma <strong>of</strong> cows and fetuses . Amer. J. Vet.<br />

Res. 54 , 164 – 167 .<br />

Ametaj , B. N. , Bradford , B. J. , Bobe , G. , Nafikov , R. A. , Lu , Y. , Young , J. W. ,<br />

and Beitz , D. C. (2005 ). Strong relationships between mediators <strong>of</strong> the<br />

acute phase response and fatty liver in dairy cows . Can. J. Anim. Sci.<br />

85 , 165 –175 .<br />

Andersen , S. B. , Wallevik , K. , and Glenert , J. ( 1963 ). Gamma globulin<br />

turnover and intestinal degradation <strong>of</strong> gamma globulin in dog . J. Clin.<br />

Invest . 42 , 1873 .<br />

Anderson , N. L. , and Anderson , N. G. ( 2002 ). The human plasma proteome<br />

. Molec. Cell. Proteom. 1 , 845 – 867 .<br />

Anderson , N. L. , Polanski , M. , Pieper , R. , Gatlin , T. , Tirumalai , R. S. ,<br />

Conrads , T. P. , Veenstra , T. D. , Adkins , J. N. , Pounds , J. G. , Fagan ,<br />

R. , and Lobley , A. ( 2004 ). The human plasma proteome: a nonredundant<br />

list developed by combination <strong>of</strong> four separate sources . Molec.<br />

Cell. Proteom. 3 , 311 – 326 .<br />

Andersson , M. , and Sevelius , E. ( 2001 ). Abnormal microheterogeneity <strong>of</strong><br />

haptoglobin in serum from dogs with various diseases . Vet. Rec. 148 ,<br />

14 – 17 .

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