Abbreviations:
a = alpha
B = beta
r = gamma
k = kappa
ACTH = adrenocorticotropic hormone
CSF = cerebrospinal fluid
DEC = states with decreased levels
DIC = disseminated intravascular coagulopathy
FP = function, properties, genetic variants
GV = genetic variant
HDL = high-density lipoprotein
HLA = human leukocyte antigen
HS = heat soluble
IDL = intermediate-density lipoprotein
INC = states with increased levels
J = joining piece
LCAT = lecithin cholesterol acyl transferase
LDL = low-dendity lipoprotein
LMW = low molecular weight
MO = electrophoretic mobility (agarose pH 8.6)
MW = molecular weight (daltons)
PMNL = polymorphonuclear leukocyte
RI = reference interval (g/l [IU/ml])
SC = secretory component
TIBC = total iron-binding capacity
VLDL = very-low-density lipoprotein
********************************************************************************
IMMUNOGLOBULINS
********************************************************************************
Immunoglobulin G (7s-r-globulin) (IgG); MW: 150,000; MO: a2 - r2
RI: 8.0 - 17.0 [92 - 196]
FP: Antibodies, esp. to viruses, bacteria, toxins
Only Ig which crosses the placenta (active transport)
Subclasses: IgG1, IgG2, IgG3, IgG4
GV: GM allotypes of r chains, KM allotypes of k chains
INC Chronic liver disease (incl. cirrhosis)
Chronic infection
Parasitic disease
Sarcoidosis
IgG myeloma
DEC Acquired immunodeficiency
Hereditary deficiencies (class or subclass)
Protein-losing syndromes
Pregnancy
Non-IgG myeloma
Waldenstrom's macroglobulinemia
================================================================================
Immunoglobulin A (IgA); MW: 160,000 and aggregates; MO: B2 - r1
RI: M: 1.0 - 4.9 [60 - 292] F: 0.85 - 4.5 [51 - 268]
FP: Antibodies subclasses: IgA1, IgA2
GV: AM allotypes of a chains, KM allotypes of k chains
INC Chronic liver disease (incl. cirrhosis)
Chronic infection, esp. GI and resp. tracts
Inflammatory bowel disease
Neoplasia of GI tract
Autoimmune disease. esp. rheumatoid arthritis
Wiskott-Aldrich syndrome
IgA myeloma (often polymerizing)
DEC Acquired immunodeficiency
Hereditary deficiencies (class or subclass)
Ataxia telangiectasia
Protein-losing syndromes
Infancy, early childhood
Non-IgA myeloma
Waldenstrom's macroglobulinemia
================================================================================
Secretory IgA (s IgA); MW: 385,000; MO: r1
FP: Antibodies, esp. in mucous secretions and colostrum [2 IgA + secretory
component (SC) + joining (J) chain]
DEC Secretory IgA deficiency
================================================================================
Immunoglobulin M (19s-r-globulin) (IgM); MW: 971,000 (pentamers); MO: r1 - r2
RI: M: 0.5 - 3.2 [58 - 368] F: 0.6 - 3.7 [69 - 425]
FP: First antibodies to appear after antigenic stimulus
Isohemagglutinins (Anti-A, -B)
May be present as monomers, esp. in infancy or with plasma cell dyscrasia
INC Acute/chronic infection, esp. viral
Waldenstrom's macroglobulinemia
Nephrotic syndrome
Autoimmune disease/Sarcoidosis
Hepatocellular disease
Estrogen/pregnancy
Hyper-IgM dysgammaglobulinemia
Congenital infection (newborn infants)
DEC Acquired immunodeficiency
Hereditary deficiencies
Protein-losing syndromes
Infancy, early childhood
Non-IgM myeloma
================================================================================
Immunoglobulin D (IgD); MW: 175,000; MO: r1
RI: < 0.15 [< 100]
FP: Antibodies
Antigen receptor on B lymphocytes
INC Autoimmune disease
Chronic infections
IgD myeloma
DEC Hereditary deficiencies/ Infancy
Acquired Immunodeficiency
Non-IgD myeloma
================================================================================
Immunoglobulin E (IgE); MW: 190,000; MO: r1
RI: < 0.0003 [< 100]
FP: Antibodies (reagins)
INC Allergies
Parasitic disease
IgE myeloma
DEC Hereditary deficiencies
Acquired immunodeficiency
Ataxia telangiectasia
Non-IgE myeloma
********************************************************************************
INHIBITORS
********************************************************************************
a1-Antitrypsin (a1-Proteinase inhibitor) (a1 Pl, a1 A); MW: 54,000; MO: a1
RI: 1.4 - 3.2 [59 - 134]
FP: Inhibits serine proteinases esp. PMNL elastase
GV: PI types; over 75 known, many hypomorphic (Z, S, P, Null, etc.)
INC Estrogen/pregnancy
Anabolic steroids
Acute phase response
Hepatocellular disease (acute or chronic)
DEC Nephrotic syndrome
Hereditary deficiency (emphysema, hepatoma; neonatal cholestasis, infantile
cirrhosis)
Terminal liver disease/Severe hepatitis
Respiratory distress syndrome of infancy
Acute pancreatitis
================================================================================
a1-Antichymotrypsin (a1X-Glycoprotein)(a1 X); MW: 68,000; MO: Slow a1 - Inter-a
RI: 0.3 - 0.6
FP: Inhibits cathepsin G. mast cell chymase
INC Acute phase response
DEC Hereditary deficiency/Infancy
Nephrotic syndrome
Status asthmaticus
================================================================================
Inter-a-Trypsin inhibitor (IaTI); MW: 160,000; MO: Inter-a
RI: 0.2 - 0.7
FP: Inhibits trypsin, acrosin, secretory proteinases
Cleaced by PMNL elastase to 2 fragments; small fragment is a high-affinity
inhibitor of most serine proteinases
Precursor of LMW inhibitor in secretions and tissues ?
INC Inflammatory disorders
Malignancy
================================================================================
Antithrombin III (heparin cofactor) (AT III); MW: 58,000; MO: Inter-a to a2
RI: 0.22 - 0.39 (plasma)
FP: Inhibits thrombin, factors Xa, XII, XI, IX; kallikrein
Activity greatly potentiated by heparin
GV: qualitative and quantitative
INC Acute phase response
Anabolic steroids
DEC Nephrotic syndrome
Hereditary deficiency (hypercoagulability)/Oral contraceptives
Disseminated intravascular coagulopathy (DIC)/Deep vein thrombosis/Lung
embolism
================================================================================
a-Thiol Proteinase Inhibitor (LMW kininogen) (a TPI); MW: 167,000 90,000
MO: a1 a2
RI: 0.3 - 0.5
FP: Inhibits thiol proteinases (cathepsins B1, C, H, L, and Ca++ -activated
neutral protease)
DEC Infancy
================================================================================
C1-Inactivator (C1 esterase inhibitor) (a2-neuraminoglycoprotein) (C1 INA)
MW: 104,000; MO: a2
RI: 0.15 - 0.35
FP: Inhibits activated complement components C1r, C1s; clotting and fibrinolytic
factors; kallikrein, plasmin
GV: quantitative and qualitative variants (some hypofunctional)
INC Acute phase response
DEC Hereditary deficiency (hereditary angioedema)
================================================================================
a2-Macroglobulin (a2 M); MW: 725,000; MO: a2
RI: M: 1.2 - 2.7 [50 - 113] F: 1.4 - 3.2 [59 - 134]
FP: Inhibits most (? all) endoproteinases, including clotting, fibrinolytic, &
complement factors
May bind/transport Zn++
GV: Xm system
INC Nephrotic syndrome
Liver disease
Diabetes mellitus
Childhood
Estrogen/pregnancy
DEC Fibrinolysis; DIC
Acute pancreatitis
Stress
Severe peptic ulcer disease
Extracorporeal circulation
(No hereditary deficiency)
================================================================================
a2-Antiplasmin (a2 AP); MW: 65,000; MO: a2
RI: 0.04 - 0.08
FP: Inhibits plasmin (fibrinolysin), kallikrein
INC Acute phase response
Diabetes mellitus
DEC Hereditary deficiency (hyperfibrinolysis)
================================================================================
Cystatin C (Post-r-globulin) (r-Trace protein); MW: 11,500; MO: Post-r
RI: Trace
FP: Inhibits cysteine
Proteinases
INC In CSF: demyelinating disorders
In urine: tubular damage
********************************************************************************
COMPLEMENT COMPONENTS
********************************************************************************
C1q (11S protein); MW: 410,000; MO: r2
RI: 0.05 - 0.25
FP: Recognition unit for complement activation via classical pathway; binds
immune aggregates with IgM, some IgGs via 6 globular "heads"
Sequence similarity to collagen
INC Acute phase response
DEC Lupus erythematosus
Lymphopenia
Hereditary deficiency
Infancy
================================================================================
C1r ; MW: 166,000 (dimer); MO: B
RI: 0.025 - 0.1
FP: Proenzyme activated by complexed C1q; activates C1s
GV
DEC Lupus erythematosus
Renal disease/Recurrent infections
Hereditary deficiency/Infancy
================================================================================
C1s ; MW: 83,000; MO: a2
RI: 0.05 - 0.1
FP: Proenzyme; binds C1q and C1r via Ca++; activates C4 and C2
GV
INC Acute phase response
DEC Lupus erythematosus
Infancy
================================================================================
C2 ; MW: 102,000; MO: B1
RI: 0.01 - 0.08
FP: Proenzyme, activated by C1, with release of kinin-like fragment; part of
C3 and C5 convertases
GV: linked to HLA, C2, factor B
INC Acute phase response
DEC Immune complex disease, esp. lupus erythematosus with nephritis
Hereditary angioedema (HANE)
Hereditary deficiency/Infancy
================================================================================
C3 (B1C-globulin); MW: 185,000; MO: B1 - B2
RI: 0.5 - 0.9 [0.64 - 1.15]
FP: C3a: cnaphylatoxin
C3b: opsonization, chemotaxis; part of C5 convertase (and C3 convertase of
altervative pathway)
GV: some hypomorphic
INC Subacute inflammation
Biliary obstruction
Nephrotic syndrome (+)
Corticosteroid therapy (+)
DEC Immune complex disease, esp. lupus erythematosus with nephritis
Acute poststreptococcal glomerulonephritis
Hypercatabolism, esp. C3b inactivator deficiency
Hereditary deficiency (recurrent infections)/infancy
================================================================================
C4 (B1E-globulin); MW: 200,000; MO: B1
RI: 0.1 - 0.4
FP: C4a: anaphylatoxin
C4b: constituent of C3 & C5 convertases in the classical pathway
GV: two loci (C4A, C4B); linked to HLA, C2, factor B
INC Acute phase response
Estrogen/pregnancy
DEC Immune complex disease, esp. lupus erythematosus with nephritis
Hereditary angioedema (HANE)
Hereditary Deficiency
Acute glomerulonephritis/Infancy
================================================================================
C5 (B1F-globulin); MW: 185,000; MO: B1
RI: 0.04 - 0.15
FP: C5a: anaphylatoxin, chemotaxis
C5b: constituent of membrane attack complex (C5b-C9)
GV (familial dysfunction)
DEC Leiner's disease (functional deficiency)
Lupus erythematosus
Hereditary deficiency (recurrent neisserial infections)
================================================================================
C6 ; MW: 104,800; MO: B2; RI: 0.04 - 0.08
C7 ; MW: 92,400; MO: B2; RI: 0.05 - 0.08
C8 ; MW: 163,000; MO: r1; RI: 0.04 - 0.08
C9 ; MW: 71,000; MO: a; RI: 0.05 - 0.25
FP: Constituents of membrane attack complex
GV
DEC Hereditary deficiency (recurrent neisserial infections)
================================================================================
Factor B (C3-proactivator; B2-glycoprotein II; glycine-rich B-glycoprotein)
MW: 90,000; MO: B1; RI: 0.1 - 0.4
FP: Proenzyme precursor of C3 activator in alternative pathway
GV (linked to C2, C4, HLA)
INC Acute phase response
DEC Lupus erythematosus, other immune complex diseases
Infections with gram-negative organisms
Sickle cell disease
================================================================================
Factor D (C3-proactivator convertase); MW: 24,000; MO: a; RI: approx. 0.01
FP: Proenzyme, activation of factor B in alternative pathway
================================================================================
Properdin (P); MW: 220,000 (tetramer); RI: 0.01 - 0.03
FP: Regulator in alternative pathway (stabilizes C3bBb)
DEC Acute glomerulonephritis
Gram-negative sepsis
================================================================================
Factor I (C3b inactivator); MW: 90,000; MO: B; RI: 0.025 - 0.05
FP: Proteolytic cleavage of C3b, C4b, C5b
DEC Hereditary deficiency (recurrent infections)
================================================================================
C4-binding Protein; MW: 540,000; MO: B2; RI: 0.18 - 0.32
FP: Enhancement of C4b cleavage (with C3bINA)
********************************************************************************
COAGULATION and FIBRINOLYSIS
********************************************************************************
Fibrinogen (F I); MW: 340,000; MO: B2; RI: 2.0 - 4.0 (plasma)
FP: Precursor of fibrin, the major constituent of blood clots
GV: qualitative and quantitative (some hypofunctional)
INC Acute phase response
Estrogens, pregnancy, oral contraceptives
DEC DIC / Hepatocellular disease
Anabolic steroids
Hereditary deficiency/Infancy
================================================================================
Prothrombin (F II); MW: 72,000; MO: a1; RI: 0.05 - 0.1 [0.5 - 1.5 kU/L)
FP: Proenzyme of thrombin, which converts fibrinogen to fibrin
Vitamin K-dependent; GV
INC Estrogens, oral contraceptives
DEC Hepatocellular disease
Vitamin K deficiency / Oral anticoagulants
Hereditary deficiency
================================================================================
Factor V (proaccelerin) (F V); MW: 330,000; MO: B; RI: < 0.03 [0.5 - 2 kU/L]
FP: Accessory factory (nonenzymatic) in the prothrombinase complex (with tissue
factor)
DEC Hepatocellular disease
Septicemia, DIC
Acquired inhibitors
Hereditary deficiency
================================================================================
Factor VII (proconvertin) (F VII); MW: 48,000; MO: a; RI: < 0.001
FP: Coactivator (with tissue factor) of extrinsic coagulation pathway
Vitamin K-dependent
INC Estrogens, oral contraceptives
Anabolic steroids
DEC Hepatocellular disease
Vitamin K deficiency / Oral anticoagulants
Aspirin, dextrothyroxine
Hereditary deficiency
================================================================================
Factor VIII:C(antihemophilic factor)(F VIII:C); MW: 92,000 & 80,000 (two chains)
MO: B; RI: < 0.001
FP: Pro-coagulant protein
Constituent of factor X activator complex
INC Acute phase response
Exercise
Late pregnancy
Uremia
DEC Acquired inhibitors
DIC (up or down)
Hereditary deficiency; hemophilia A (X-linked)
================================================================================
Factor VIII-Related Antigen (F VIII:RAg) (von Willebrand factor) (VWF)
MW: 1,000,000; MO: B; RI: 0.005 - 0.01
FP: Normally complexed with F VIII procoagulant
Essential for platelet aggregation
INC Acute phase response
Exercise
Uremia
DEC Hereditary deficiency (von Willebrand's disease), autosomal dominant
================================================================================
Factor IX (Christmas factor) (F IX); MW: 51,800; MO: a1; RI: 0.005 - 0.01
FP: Proenzyme, constituent of factor X activation complex
Vitamin K-dependent
GV
INC Estrogens
Glucocorticosteroids
DEC Hepatocellular disease
Vitamin K deficiency / oral anticoagulants
Hereditary deficiency: hemophilia B (Christmas disease) (X-linked)
================================================================================
Factor X (Stuart-Prower factor) (F X); MW: 59,000; MO: a1; RI: 0.005 - 0.01
FP: Proenzyme, constituent of prothrombin activator complex
Vitamin-K dependent; GV
INC Anabolic steroids
Estrogens
DEC Hepatocellular disease / Amyloidosis
Vitamin K deficiency / Oral anticoagulants
Hereditary deficiency
================================================================================
Factor XI (plasma thromboplastin antecedant) (F XI); MW: 130,000
RI: 0.004 - 0.006
FP: Proenzyme, activated by factor XIIa; activates factor IX
DEC Hereditary deficiency; hemophilia C
DIC
================================================================================
Factor XII (Hageman factor) ("glass factor" - ed.) (F XII); MW: 76,000
MO: a; RI: 0.015 - 0.05
FP: Proenzyme, activated by surface contact; activates factor XI, with HMW
kininogen
F XIIa also activates complement, kallikrein, fibrinolytic systems
INC Oral contraceptives
DEC Hereditary deficiency
DIC
================================================================================
Factor XIII (fibrin stabilizing factor) (F XIII); MW: 320,000; MO: a
RI: 0.01 - 0.04
FP: Transamidase; cross-linking of fibrin monomers to stabilize blood clots
DEC Hepatocellular disease
Hereditary deficiency
DIC
================================================================================
High-Molecular-Weight (HMW) Kininogen (Fitzgerald factor); MW: 197,000
MO: a; RI: 0.09 +/-
FP: Accessory in contact-phase activation
DEC Chronic renal failure
Hepatic cirrhosis
DIC
================================================================================
Prekallikrein (Fletcher factor); MW: 95,000; MO: a; RI: 0.09 - 0.11
FP: Proenzyme; enzymatic and accessory function in contact-phase activation
DEC Severe liver disease
Fibrinolysis, DIC/Uremia
Hereditary deficiency/Infancy
================================================================================
Plasminogen ; MW: 91,000; MO: B; RI: 0.06 - 0.25 (plasma)
FP: Proenzyme of plasmin (fibrinolysin), which lyses fibrin clots
Activated by tissue plasminogen activators (tPA), streptokinase, urokinase
Affinity binding to fibrin (?)
GV: some hypofunctional
INC Anabolic steroids
Estrogens/pregnancy
Rigorous exercise
DEC Fibrinolytic therapy
Severe liver disease
DIC
Fetus/Infancy
Infant respiratory distress syndrome
================================================================================
Protein C; MW: 62,000; RI: approx. 0.001
FP: Proenzyme "anticoagulant"; inactivates factors Va and VIIIa by limited
proteolysis; vitamin K-dependent
DEC Hereditary deficiency
Vitamin K deficiency
Oral anticoagulants
================================================================================
Protein S; MW: 69,000; RI: Trace
FP: Enhances activity of protein C
Two forms in plasma, free and complexed to C4 binding protein
Vitamin K-dependent
DEC Hereditary deficiency
Vitamin K deficiency
Oral anticoagulants
********************************************************************************
BINDING / TRANSPORT
********************************************************************************
Albumin (ALB); MW: 66,460; MO: Albumin; RI: 37 - 53 [93 - 133]
FP: Maintenance of oncotic osmotic pressure
Transport of fatty acids, bilirubin, metal ions
GV of albumin and proalbumin
INC Dehydration
Intravenous infusion
DEC Acute phase response
Chronic inflammation
Malnutrition/Protein-losing syndromes
Fluid shifts/Overhydration
Hereditary deficiency
================================================================================
Haptoglobin (HP); MO: a2; RI: 0.5 - 3.2
Hp 1-1: MW: 86,018 RI: 1.0 - 2.3
Hp 2-1: MW: 86,018+ polymers RI: 0.9 - 3.2
Hp 2-2: MW: > 200,000 (polymers) RI: 0.5 - 3.2
FP: Binds free hemoglobin, resulting in: peroxidase activity and preservation
of body iron
Tetrameric (2a, 2B chains); Hp 2 forms polymers
GV: qualitative, quantitative
INC Acute phase response
Glucocorticoids
Hodgkin's disease
Anabolic steroids
Biliary obstruction
Nephrotic syndrome (Hp 2-1 or 2-2)
Ulcerative colitis
DEC In vivo hemolysis or ineffective erythropoiesis
Estrogen/Pregnancy
Active hepatocellular disease
Nephrotic syndrome (Hp 1-1)
Infancy
================================================================================
Prealbumin (transthyretin, thyroxine-binding prealbumin); MW: 54,980 (tetramer)
MO: Prealbumin; RI: 0.25 - 0.45
FP: Binds and transports T3/T4 & retinol-binding protein
GV: some ? associated with familial amyloidosis
INC Glucocorticosteroids
Hodgkin's disease
Nonsteroidal anti-inflammitory therapy
Alcoholism (without hepatocellular disease)
DEC Acute phase response
Hepatocellular disease
Malnutrition
Nephrotic syndrome
Infancy, early childhood
Estrogens/Pregnancy
================================================================================
Retinol-binding Protein (RBP); MW: 20,960; MO: a2 alone; Prealbumin complexed
RI: 0.03 - 0.06
FP: Binds and transports retinol (vitamin A); essential for cellular
recognition and uptake of vitamin A
Complexed 1:1 with prealbumin; concentrations correlate except with
vitamin A deficiency
INC Glucocorticosteroids
Oral contraceptives
Renal failure
DEC Acute phase response
Hepatocellular disease
Malnutrition
Nephrotic syndrome
Hyperthyroidism
Vitamin A deficiency
================================================================================
Thyroxine-binding Globulin (TBG); MW: 54,000 MO: a1 to Inter-a
RI: 0.01 - 0.03
FP: Binds and transports T3, T4
GV: qualitative and quantitative (X-linked)
INC Estrogen/Pregnancy
Hereditary excess
Hepatitis B
Hypothyroidism (+/-)
DEC Acute phase response
Anabolic steroids
Glucocorticoids
Hyperthyroidism
Malnutrition
Nephrotic syndrome
Hereditary deficiency (X-linked)
================================================================================
Transcortin (corticosteroid-binding globulin) (CBG); MW: 55,700; MO: Inter-a
RI: 0.015 - 0.02
FP: Binds and transports cortisol, etc.
INC Estrogen/Pregnancy
DEC Anabolic steroids
Ovarian hypofunction
================================================================================
Sex hormone-binding Globulin (Steroid-binding B Globulin) (SHBG); MW: 115,000
MO: B1; RI: M: 0.001 - 0.012 F: 0.003 - 0.015
FP: Binds and transports testosterone, estradiol, etc.
INC Estrogen/Pregnancy
DEC Anabolic steroids
Thyroid hormones
Groth hormone
================================================================================
Vitamin D-binding Protein (Gc-globulin, group specific component) (VDBP)
MW: 50,800; MO: Inter-a to a2
RI: 0.2 - 0.55
FP: Binds and transports vitamin D3; binds/scavenges actin
GV: GC (over 50 alleles)
INC Estrogen/Pregnancy
DEC Severe liver disease
Protein-losing syndromes
Infancy
================================================================================
Transcobalamin I (TC I); MW: 65,000; MO: a1; RI: Trace
FP: Rapid binder of vitamin B12
INC Hepatoma
Polycythemia
Myeloid leukemia
================================================================================
Transcobalamin II (TC II); MW: 53,900; MO: B1; RI: > 25 ng/L
FP: High-turnover vitamin B12 binding and transport
GV: including hypofunctional
INC Myeloproliferative disorders
DEC Hereditary deficiency
Infancy
================================================================================
Transferrin (siderophilin) (TF); MW: 79,550; MO: B1
RI: 2.3 - 4.3 [80 - 150]
FP: The major binding/transport protein for iron; 1 mg = 1.25 ug Fe+++ in total
iron-binding capacity (TIBC)
Unsaturated transferrin (or low free iron) may be important in control of
infections, parasitic infestations
GV: over 20 known
INC Iron deficiency
Estrogen/Pregnancy
DEC Acute phase response
Chronic inflammation
Malnutrition
Hemochromatosis
Protein-losing syndromes
Hereditary deficiency (severe hypochromic anemia)
================================================================================
Ferritin ; MW: 450,000
RI: M: 30 - 220 ug/L F: 20 - 110 ug/L
FP: Plasma concentration proportional to iron stores except with acute phase
Primary iron storage protein in most body tissues, esp. liver, spleen, bone
marrow
INC Iron overload, esp. hemochromatosis and chronic transfusion
Acute/chronic inflammation
Active liver disease
DEC Iron deficiency
Generalized malnutrition
================================================================================
Hemopexin (HPX); MW: 60,000; MO: B1; RI: 0.5 - 1.15
FP: Binds free heme, conserving body iron
INC Estrogen/Pregnancy
Acute phase response
DEC Severe in vivo hemolysis
Nephrotic syndrome
Infancy
********************************************************************************
APOLIPOPROTEINS
********************************************************************************
Apolipoprotein A
Apo A-I: MW: 28,020 MO: a1; RI: 1.15 - 2.1
FP: Major protein constituent of high-density lipoprotein (HDL); activates
lecithin-cholesterol acyl transferase (LCAT) in vitro
Stabilizes prostacyclin, reduces platelet aggregation
GV: some malfunctional
INC Estrogen/Pregnancy
Exercise
Familial increase
Liver disease
(Increase is associated with decreased risk for atherosclerosis)
DEC Familial Hypo-a-lipoproteinemia
Tangier disease (hereditary)
"Fish-eye" disease (hereditary)
Cholestasis; sepsis
(Decrease is associated with increased risk for atherosclerosis)
Apo A-II: MW: 17,440; MO: a1; RI: 0.26 - 0.66
FP: Structural component of HDL; function otherwise unknown; GV
DEC Cholestasis
================================================================================
Apolipoprotein B
Apo B-48: MW: approx. 250,000; MO: B; RI: (Varies with dietary status)
FP: Major protein of chylomicrons; synthesized by intestine
INC Liver disease
Apo B-100: MW: approx. 514,000; MO: B; RI: 0.65 - 1.55
FP: Primary protein component of low-density lipoproteins (LDL) and very-low-
density lipoproteins (VLDL)
Cholesterol transport; ligand for LDL (apo B/E) receptors
Synthesized primarily in the liver
GV: at least one qualitative variant is associated with elevated LDL
INC Pregnancy, progestins
Familial hypercholesterolemia
Familial hyper apobetalipoproteinemia
Nephrotic syndrome
Biliary obstruction
Type II hyperlipidemia
(Increase is associated with increased risk for atherosclerosis)
DEC Estrogens
Familial hypobetalipoproteinemia
Abetalipoproteinemia
Sepsis
Liver disease
(Decrease is associated with decreased risk for atherosclerosis)
================================================================================
Apolipoprotein C
Apo C-I: MW: 6,630; RI: 0.04 - 0.06
FP: Minor component of most lipoproteins, esp. VLDL, chylomicrons, chylomicron
remnants
May activate LCAT
Apo C-II: MW: 8,824; RI: 0.03 - 0.05
FP: Lipoprotein lipase activation (with apolipoprotein H)
Most found in VLDL, chylomicrons
GV: qualitative, quantitative (some nonfunctional)
DEC Hereditary deficiency (autosomal recessive; very high triglycerides)
Apo C-III: MW: 8,764; RI: 0.12 - 0.16
FP: Inhibits remnant uptake by interfering with ApoE receptor
May modulate lipoprotein lipase activity
GV: one qualitative variant associated with hypertriglyceridemia
DEC Combined hereditary deficiency with ApoA-I (with decreased HDL and increased
risk for atherosclerosis)
================================================================================
Apolipoprotein E (apo E); MW: 34,145; RI: M: 0.02 - 0.06 F: 0.015 - 0.04
FP: Constituent of chylomicron remnants, VLDL, intermediate-density lipoproteins
(IDL), LDL, some HDL; ligand for ApoE and B/E receptors (removal of lipids,
esp. by liver)
GV: most individuals with type III hyperlipidemia are phenotype E2/2
INC Familial increase
Pregnancy
Dexamethasone
Cholestasis
In cerebrospinal fluid (CSF): remyelination (e.g., recovery phase of
multiple sclerosis)
DEC Familial decrease
Adrenocorticortropic hormone (ACTH)
Liver disease
================================================================================
Apolipoprotein (a) (apo (a)); MW: approx. 280,000 (varies with phenotype)
MO: Pre-B; RI: 0.01 - 1.4 (varies with phenotype)
FP: Constituent of Lp(a), bound to apo B-100 via disulfide linkage. Atherogenic
Partial sequence homology with plasminogen; blocks plasminogen binding to
fibrin clots ?
GV: qualitative, quantitative
INC Hereditary elevation
DEC Hereditary decrease
Anabolic steroids
================================================================================
Serum Amyloid A (SAA); MW: 11,685 (100,000 - 180,000 in serum); RI: < 0.001
FP: Present in HDL fraction; function unknown
Precursor to amyloid a fibrils ?
INC Acute phase response (300 - 500 x increase)
Pregnancy
Amyloidosis
********************************************************************************
OTHER
********************************************************************************
a-fetoprotein (AFP); MW: 66,300; MO: a1; RI: < 10 ug/L [<7]
FP: Fetoembryonal analogue of albumin, with similar function thereto;
senthesized by yolk sac and fetal liver
(Some fractions may bind estrogens and/or be immunosuppressive)
INC Infancy/Pregnancy
Hepatocellular cancer, esp. hepatoblastoma
Choriocarcinoma/teratoma, esp. of testis/ovary
Acute hepatitis/Hepatic regeneration
Ataxia telangiectasia
Hereditary tyrosinemia
Congenital hypothyroidism
maternal serum: open fetal defects of neural tubes, abdominal wall; twin
pregnancy; etc.
DEC In maternal serum: fetal death; trisomy 21
================================================================================
a1-Acid Glycoprotein (orosomucoid) (a1 AG); MW: 41,000
RI: M: 0.50 - 1.30 F: 0.40 - 1.20
FP: Binds (? inactivates) basic hormones, drugs (e.g. progesterone, propanolol)
Suppresses immunoreactivity
Modifies platelet adhesiveness
GV: two loci (ORM1, ORM2)
INC Acute phase response
Glucocorticoids (endogenous/exogenous)
Physical exertion
Renal failure
DEC Estrogen/Pregnancy
Protein-losing syndromes
Severe liver disease
Infancy
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Ceruloplasmin (CER); MW: 132,000; MO: Inter-a to a2
RI: 0.20 - 0.55 [64 - 176]
FP: Reduction/oxidation; ferrioxidase; oxygen radical scavenger
Transports Cu++ (1% by alb) ?
Very susceptible to proteolytic degradation
GV
INC Estrogen/Pregnancy
Acute phase response
Reticuloendothelial disease (e.g., Hodgkin's disease)
Biliary obstruction
DEC Hereditary deficiency (iron storage disease)
Secondary deficiency: Wilson's disease (hepatocellular degeneration);
Menke's steely (kinky) hair syndrome
Copper deficiency
Severe liver disease
Nephrotic syndrome
Infancy
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Serum Amyloid P Protein (9.5s a1-glycoprotein; a1-macroglobulin) (SAP)
MW: 233,000 - 308,000; MO: a1; RI: 0.035 - 0.075
FP: Constituent of amyloid deposits; lecithin-like properties
High affinity for polyanions and cations, fibronectin
Pentagonal (double pentamers); much sequence and structural homology with
C-reactive protein
DEC Hepatocellular disease
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a2-HS Glycoprotein (a2 HS); MW: 50,000; MO: a2; RI: 0.40 - 0.85
FP: Component of bone matrix and dentin; affinity for Ca++, Zn++
Opsonic properties ?
Depresses cell-mediated immunity ?
GV
DEC Acute phase response
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Fibronectin (cold insoluble globulin) (FN); MW: 440,000 +/-; MO: a2 - B1
RI: 0.25 - 0.4
FP: Promotes cell-cell adhesion
Binds to fibrin (clots) and C1q (immune complexes), resulting in
opsonization and fibroblast adherence
INC Chronic active hepatitis
DEC Acute phase response
Sepsis; shock; DIC
Acute leukemia
Acute pancreatitis
Hereditary deficiency
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C-reactive Protein (CRP); MW: 105,000 - 114,700
MO: B - r2 (Depending on Ca++ concentration); RI: < 0.005
FP: Activates complement (Ca++ dependent), resulting in early, nonimmune
clearance of gram-negative bacteria and ? tissue breakdown products
A pentraxin, structurally related to serum amyloid P
Binds phosphorylcholine in the presence of Ca++
INC Acute phase response (up to 1000 x increase)
DEC Infancy
(no reported hereditary deficiency)
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B2-Microglobulin (B2 M); MW: 11,818; MO: B2; RI: 0.001 - 0.003
FP: Component of human leukocyte antigen (HLA) molecules class I
INC B-cell malignancies
Renal failure
Fetal/neonatal period
In urine: proximal renal tubular disease; renal transplant rejection
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Pregnancy-specific B1-glycoprotein (SP1); MW: 90,000 (42,300) n; MO: B1
RI: < 1/1,000,000
FP: Binds and transports steroid hormones
Synthesized by the syncytiotrophoblast; concentration proportional to
placental weight
INC Pregnancy
Trophoblastic disease
Malignant teratomas
Twin pregnancy
DEC "Blighted ovum"
Preceeding spontaneous abortion
Placental insufficiency
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a1-Microglobulin (a1 M); MW: approx. 33,000; MO: a1; RI: 0.02 - 0.05
FP: Immunosuppression
Binds lipophilic molecules (a lipocalin, related to retinol binding protein
and a1-acid glycoprotein)
INC Renal insufficiency
In urine: tubular proteinuria
================================================================================
Compiled by Andrew Myron Johnson, MD, Director, Rheumatic Disease Laboratory, Scarbrough, Maine, USA. Adapted and Edited by W. Irving Crowley, MT, Chief Technologist Edge Regional Medical Center Laboratory, Troy, Alabama, USA (C) 1989, 2001
