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paroxysmal cold hemoglobinuria (PCH) 556 passive agglutination
atrophy of the fundal mucosa, achlororhydria, tendency to
evolve into pernicious anemia, and association with autoimmune
endocrine disease are characteristic. PCAs can be
detected by incomplete Freund’s adjuvant (IFA) as reticular
cytoplasmic staining using mouse stomach frozen sections.
PCAs have been found in 100% of patients with primary
biliary cirrhosis, in three fourths of cases of autoimmune
hepatitis, and in 29% of patients with chronic liver disease.
paroxysmal cold hemoglobinuria (PCH)
A rare type of disease that accounts for 10% of cold autoimmune
hemolytic anemias. It may be a primary idiopathic
disease or secondary to syphilis or viral infection and is
characterized by the passage of hemoglobin in the urine after
exposure to cold. In addition to passing dark brown urine,
a patient may experience chills, fever, and pain in the back,
legs, or abdomen. The disease is associated with a hemolysin
termed the Donath–Landsteiner antibody, a polyclonal immunoglobulin
G (IgG) antibody. It sensitizes red blood cells in
the cold, complement attaches to the erythrocyte surface, and
hemolysis occurs on warming to 37°C. The specificity of the
antibody is for the P antigen of red blood cells.
paroxysmal nocturnal hemoglobinuria (PNH)
A rare form of hemolytic anemia in which the red blood
cells, neutrophils, and platelets manifest strikingly increased
sensitivity to complement lysis. An acquired membrane defect
secondary to a mutation that affects myeloid stem cells. The
mutant PIGA gene is requisite for the synthesis of a precise
intramembranous glycolipid anchor called phosphatidyl inositol
glycan (PIG), a component of diverse membrane-associated
proteins. This membrane anchor is necessary for the expression
of PIG-tailed proteins on cell surfaces. The affected proteins
include some that limit the spontaneous activation of complement
at the cell surface. Thus, PIG-deficient precursors give
rise to red cells that are especially sensitive to the lytic action of
complement. The hemolysis is nocturnal as the blood becomes
acidic during sleep because of CO 2 retention and an acid pH
may facilitate hemolysis. PNH red blood cell membranes are
deficient in decay-accelerating factor (DAF), leukocyte-function-associated
antigen 3 (LFA-3), and FcRIII. Without DAF,
which protects the cell membranes from complement lysis
by classic pathway C5 convertase and decreases membrane
attack complex formation, the erythrocytes and lymphocytes
are highly susceptible to lysis by complement. Interaction of
these PNH erythrocytes with activated complement results in
excessive C3b binding, which leads to the formation of more
C3b through the alternate complement pathway by way of
factors B and D. Intravascular hemolysis follows activation
of C5 convertase in the C5–C9 membrane attack complex
(MAC). The blood platelets and myelocytes in affected subjects
are also DAF-deficient and are readily lysed by complement.
Leukopenia, thrombocytopenia, iron deficiency, and
diminished leukocyte alkaline phosphatase are observed. The
Coombs’ test is negative, and acetylcholine esterase activity in
the red cell membrane is very low. No antibody participating in
this process has been found in either the serum or on the erythrocytes.
The disease is suggested by episodes of intravascular
hemolysis, iron deficiency, and hemosiderin in the urine. It is
confirmed by hemolysis in acid medium, termed the HAM test.
partial agonist
Refer to altered peptide ligands.
partial identity
Refer to reaction of partial identity.
parvovirus
A minute icosahedral virus composed of single-stranded
DNA that may replicate in previously uninfected host cells
or in those already infected with adenovirus.
parvovirus immunity
Specific immunoglobulin M (IgM) followed by IgG antibodies
that occur in the second week of exposure can effectively
clear parvovirus infection. Parvovirus B19 targets
the erythroid bone marrow cells. Antibodies that develop
following first exposure to the virus are specific mainly for
VP2 epitopes. This is followed by antibodies that are specific
for VP1 epitopes. VP1-unique region linear epitopes
are critical to induce effective neutralizing antibodies. IgG
antibodies persist for life. Immunodeficient individuals who
cannot develop adequate antibody responses may develop
persistent parvovirus infection. VP1-specific antibodies
are crucial for the control of parvovirus B19 infection.
Commercial immunoglobulin preparations contain
parvovirus B19 neutralizing antibody and are useful for
the treatment of persistent parvovirus infection. Antibody
synthesis in immunocompetent subjects prevents clinical
manifestations as a consequence of direct viral cytotoxicity.
Immunodeficient patients who have impaired capacity to
synthesize neutralizing antibodies develop severe anemia
as a result of suppressed erythropoiesis by the virus. Empty
parvovirus capsids enriched for VP1 epitopes induce protective
antibody responses. A recombinant form has shown
promise in clinical trials.
PAS
(1) Abbreviation for periodic acid Schiff stain for polysaccharides.
This technique identifies mucopolysaccharide,
glycogen, and sialic acid among other chemicals containing
1,2-diol groups. (2) Abbreviation for para-aminosalicylic
acid, used in the treatment of tuberculosis.
passive agglutination
The aggregation of particles with soluble antigens adsorbed
to their surfaces by a homologous antibody. The soluble antigen
may be linked to the particle surface through covalent
bonds rather than by mere adsorption. Red blood cells, latex,
bentonite, or collodion particles may be used as carriers for
antigen molecules adsorbed to their surfaces. When a red
blood cell is used as a carrier particle, its surface has to be
altered to facilitate maximal adsorption of the antigen to its
surface. Several techniques are employed to accomplish this.
One is the tanned red blood cell technique, which involves
treating the cells with a tannic acid solution that alters
their surfaces in a manner favoring the adsorption of added
soluble antigen. A second method is the treatment of red cell
preparations with other chemicals such as bis-diazotized
benzidine. With this passive agglutination technique, even
relatively minute quantities of soluble antigens may be
detected by the homologous antibody-agglutinating carrier
cells on which they are adsorbed. Because red blood cells
are the most commonly employed particles, the technique is
referred to as passive hemagglutination. Latex particles are
used in the rheumatoid arthritis (RA) test, in which pooled
immunoglobulin G (IgG) molecules are adsorbed to latex
particles and reacted with the sera of patients with rheumatoid
arthritis that contain rheumatoid factor (IgM anti-IgG
antibody) to produce agglutination. Polysaccharide antigens
will stick to red blood cells without treatment. When proteins
are used, however, covalent linkages are required.