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WILLIAM'S HEMATOLOGY > 137 Human Leukocyte and Platelet Antigens > Flashcards

137 Human Leukocyte and Platelet Antigens Flashcards

1
Q

The human leukocyte antigens (HLAs) are highly polymorphic glycoproteins encoded by a region of genes known as the major histocompatibility complex (MHC) located on the short arm of chromosome ________________

A

Chromosome 6p21

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2
Q

Their biologic function of human leukocyte antigens (HLAs)

A

Present donor-specific antigenic peptides to T lymphocytes and/or stimulate B cells to further differentiate to plasma cells and produce donor antigen–specific antibodies (DSA)

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3
Q

Class I HLAs

A

HLA-A, HLA-B, and HLA-C

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4
Q

Class II HLAs

A

HLA-DR, HLA-DQ, and HLA-DP

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5
Q

Type of HLA

Ubiquitous and present on most nucleated somatic cells, including those involved in the innate and adaptive immune response

A

Class I antigens

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6
Q

TRUE OR FALSE

Platelets express HLA-A antigens, but lack some HLA-B and most HLA-C antigens.

A

TRUE

Platelets express HLA-A antigens, but lack some HLA-B and most HLA-C antigens.

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7
Q

Type of HLA

More restricted distribution, with varying levels of expression on B cells, dendritic cells, monocytes, and macrophages

Present peptides from exogenous sources, such as bacterial pathogens, to CD4+ T cells.

Initial biomarker of inflammation and rejection

A

Class II antigens

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8
Q

Nonclassical class Ib antigens

A

HLA-E, HLA-F, and HLA-G

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9
Q

Type of HLA

Group of genes and their products may have a pivotal role in maternal acceptance of a fetus as well as in other pathways involved in immune tolerance

A

Class I HLA-G

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10
Q

TRUE OR FALSE

HLA antigens are codominantly inherited so that each individual expresses two antigens, one from each parent, at each locus (A, B, DR, etc)

A

TRUE

HLA antigens are codominantly inherited so that each individual expresses two antigens, one from each parent, at each locus (A, B, DR, etc)

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11
Q

Class I Antigens

Region of the alpha chain comprising the antigen recognition domain (ARD) , the areas of highest polymorphism

A

α1 and α2 regions

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12
Q

TRUE OR FALSE

The β chain of HLA-DR is constant for all HLA-DR molecules, whereas the α chain is polymorphic and determines specificity of the molecule.

A

FALSE

The α chain of HLA-DR is constant for all HLA-DR molecules, whereas the β chain is polymorphic and determines specificity of the molecule.

In contrast, HLA-DQ and DP molecules exhibit polymorphism in both α and β chains, with the β chain displaying the greatest variability

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13
Q

The identification of each HLA antigen of an individual is called

A

Phenotype

  • Each individual has one allele for each locus per chromosome and therefore encodes two HLA antigens per locus.
  • Because HLA genes are closely linked, recombination within the MHC is rare (≤1%), and a complete set of HLA genes usually is inherited from each parent as a unit.
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14
Q

The genes inherited from each parent are referred to as a

A

Haplotype

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15
Q

Family studies consist of typing for HLA:

A

HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP

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16
Q

Added to the list of determinants for transplant compatibility

Used in the in the solid organ arena, where antibodies to these antigens have been implicated in rejection

A

DPA1* and DQA1* antigens

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17
Q

What is Linkage Disequilibrium

A

HLA alleles are inherited together on the same chromosome more often than would be predicted if HLA loci were in equilibrium.

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18
Q

Serologic Testing for HLA that has been the benchmark procedure in HLA testing in the field of transplant immunology for more than 50 years.

A

Complement-dependent microlymphocytotoxicity (CDC) assay

  • It can be used for both HLA typing and the detection of HLA-specific antibodies.
  • The third use of the CDC assay is in performance of a crossmatch between a potential donor’s cells and patient serum.
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19
Q

CDC Assay

The number of wells that show cell death in the panel divided by the total number of microtiter wells gives one a relative indication of the serum’s antibody “strength” is called

A

Panel reactive antibody (PRA)

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20
Q

Low or High-resolution Typing

Used in HSCT

A

High-resolution Typing

  • Typing for solid organ transplantation usually requires a serologic or antigen-level identification commonly referred to as “low-resolution typing.”
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21
Q

The most common form of Molecular Human Leukocyte Antigen Typing used in HLA typing is

A

Dye-terminator sequencing

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22
Q

Advantages of NGS compared with other HLA sequencing technologies

A
  • The ability to batch samples from several patients into a single sequencing reaction
  • Ability to obtain sequencing results from a single DNA molecule, with near complete coverage of all exons and introns comprising the 11 HLA genes.
  • NGS eliminates phasing ambiguities that occur in SBT.
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23
Q

The gold standard for evaluating recipients and donors for allograft transplantation.

A

Flow cytometric crossmatch

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24
Q

TRUE OR FALSE

HLA matching is currently not performed prospectively for renal, hepatic, lung, or cardiac transplantation.

A

TRUE

HLA matching is currently not performed prospectively for renal, hepatic, lung, or cardiac transplantation.

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25
Q

Detection of alloantibody by screening techniques and the donor-specific crossmatch is of prime importance for _________________transplants, where, if undetected, their existence could cause a hyperacute rejection and graft failure.

A

Kidney, lung, and heart transplants

HLA typing for matching of kidneys and pancreases is performed at the HLA-A, HLA-B, and HLA-DR loci at low resolution (serologic or antigen level by DNA).

26
Q

To determine the best match and diminish the possibility of GVHD, HLA typing for HSCT are generally performed by molecular methods at high resolution (allele-level) typing for __________________-

A

HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP

27
Q

Patients requiring platelet transfusions may be broadly sensitized to _________ (ie, have high PRAs) through prior transfusions (particularly nonleukoreduced cellular products) or pregnancies.

A

HLA-A, and B

Determining the HLA type and/or HLA antibody profiles of these patients allows for the selection of more appropriate platelet donors (either HLA-matched, or donors selected to avoid a patient’s HLA antibody specificity), enabling these refractory patients to achieve improved platelet increments.

28
Q

HLA disease associations

  • _______: ankylosing spondylitis
  • _______: narcolepsy
  • _______: celiac disease
A
  • HLA-B27: ankylosing spondylitis
  • HLA-DQ2: narcolepsy
  • HLA-DQ2 and DQ8: celiac disease
29
Q

HLA typing is also required before the administration of certain drugs to prevent drug hypersensitivity reactions

HLA-B*5701 : _______

A

HLA-B*5701 : abacavir

30
Q

Clinically significant alloantigens expressed only or predominantly by neutrophils

A

Human neutrophil antigens (HNAs)

  • The neutrophil-specific HNA-1 antigen system consists of four epitopes—HNA-1a, -1b, -1c, and -1d—encoded by five alleles
31
Q

HNA-1 antigens are located on the low-affinity _________________, and are expressed only on neutrophils.

A

Fcγ receptor IIIb (FcγRIIIb), CD16

32
Q

FcγRIIIb and HNA-1 antigens are expressed on all segmented neutrophils, on approximately one-half of neutrophilic ____________, and on approximately 10% of neutrophilic _________________.

A
  • All segmented neutrophils
  • One-half of neutrophilic metamyelocytes
  • 10% of neutrophilic myelocytes
33
Q

HNA-1 Antigens

Among Caucasians, _______ is the most common antigen but in Asian populations, ________ is most common.

A

Caucasians: HNA-1b

Asian: HNA-1a

34
Q

TRUE OR FALSE

Function of HNA-1 Antigens

Neutrophils that are homozygous for HNA-1a have a lower affinity for immunoglobulin (Ig) G3 than those homozygous for HNA-1b.

A

FALSE

Neutrophils that are homozygous for HNA-1b have a lower affinity for immunoglobulin (Ig) G3 than those homozygous for HNA-1a.

Neutrophils from those who are homozygous for HNA-1b phagocytize erythrocytes sensitized with IgG1 and IgG3 anti-Rh monoclonal antibodies and bacteria opsonized with IgG1 at a lower level than neutrophils homozygous for HNA-1a

35
Q

Only HNA expressed on subpopulations, but not all neutrophils

A

HNA-2

HNA-2 is expressed only on neutrophils, neutrophilic metamyelocytes, and neutrophilic myelocytes.

36
Q

The encoding gene of the glycoprotein carrying HNA-2, NB1 glycoprotein, is located on neutrophil plasma membranes and secondary granules and is GPI-anchored

A

CD177

Located on chromosome 19q13.31

37
Q

TRUE OR FALSE

The mean fraction of HNA-2–positive neutrophils is 45% to 65% and is gender dependent, higher in women than men.

A

TRUE

The mean fraction of HNA-2–positive neutrophils is 45% to 65% and is gender dependent, higher in women than men.

Neutrophil expression of HNA-2 increases in infection and in Molecular Human Leukocyte Antigen Typing.

38
Q

Function of CD177

A

Binds to platelet endothelial cell-adhesion molecule-1 (PECAM-1, CD31), functioning as a cell-adhesion molecule and mediating neutrophil transendothelial migration.

39
Q

Antibodies against cochlear _____have been associated with autoimmune hearing loss.

A

HNA-3

The HNA-3 antigen system is expressed by neutrophils, lymphocytes, platelets, pulmonary endothelial cells, several solid organs, and cells in the inner ear.

40
Q

Neutrophil antigens are located on β2 integrins

A

HNA-4 and HNA-5 antigens

41
Q

First described as Marta, is expressed on the αM chain (CD11b) of αM/β2 and is present on neutrophils, monocytes, and natural killer cells

With leukocyte activation, the complex mediates vascular adhesion and migration, oxidative burst activity, and phagocytosis

A

HNA-4

42
Q

Was first described as Onda.

Expressed on the αL integrin subunit (CD11a) encoded by the ITGAL gene at chromosome 6p11.2.78

A

HNA-5a

43
Q

Clinical syndromes associated with antibodies against neutrophil antigens

A
  • ANN
  • Autoimmune neutropenia (AIN)
  • Immune neutropenia after HSCT
  • Transfusion-related acute lung injury (TRALI)
  • Transfusion-related alloimmune neutropenia
  • Refractoriness to granulocyte transfusion
  • Febrile transfusion reactions
44
Q

TRUE OR FALSE

In Alloimmune Neonatal Neutropenia, isolated neutropenia can be complicated by infections, but the cytopenia resolves as the antibody is cleared over 1 to 6 months.

A

TRUE

In Alloimmune Neonatal Neutropenia, isolated neutropenia can be complicated by infections, but the cytopenia resolves as the antibody is cleared over 1 to 6 months.

  • Most often the neutropenia is detected in the first week of life when the neonate becomes febrile or develops an infection and a neutrophil count is performed.
  • Typically, the counts are 0.1 to 0.2 × 109/L.
  • The mean duration of neutropenia has been reported to be approximately 11 weeks
45
Q

In Alloimmune Neonatal Neutropenia, granulocyte colony-stimulating factor (G-CSF) has been successfully used in more severe cases, but resistance has been reported with HNA-_______ antibodies

A

HNA-2 antibodies

Possibly resulting from G-CSF–induced increase in HNA-2 expression

46
Q

Most commonly observed antibodies in Alloimune Neonatal Neutropenia

A

Antibodies to HNA-1a, HNA- 1b, FcγRIIIb, and HNA-2

But antibodies to all HNA epitopes have been reported as causative.

47
Q

HNA-related Autoimmune Neutropenia is primarily a disease of children.

Typically, the onset of AIN in children begins at ___________ months of age

A

5 to 15 months of age

Most studies have found that neutrophil counts recover spontaneously in most patients by the age of 5 years, with a median duration of neutropenia of 13 to 20 months.

The antibodies are predominantly specific to epitopes located on FcγRIIIb

48
Q

Treatment for AIN the most reliable and sustained effect on neutrophil counts

A

G-CSF

Others: glucocorticoids, IV immunoglobulin

49
Q

Febrile transfusion reactions can be prevented in recipients of platelet and red blood cell component transfusions by

A

Leukocyte-reduced blood components

50
Q

Can result from the transfusion of neutrophil-activating antibodies or nonantibody biological response modifiers from cellular products in the plasma portion of the blood component

Diagnosed within 6 hours of a transfusion when hypoxia (oxygen saturation <90% or a partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio <300) and noncardiogenic pulmonary edema occur

A

TRALI

Symptoms and signs should be present without risk factors for acute respiratory distress syndrome or mild acute respiratory distress syndrome, or in their presence when pulmonary status has been stable in the 12 hours before transfusion.

51
Q

Mechanism of TRALI

HNA and some HLA class I antibodies:

HLA class II antibodies:

A

HNA and some HLA class I antibodies: directly activating neutrophils

HLA class II antibodies: indirectly activate neutrophils via activated monocytes

Case series have associated TRALI with the transfusion of (in decreasing frequency) monocyte-activating HLA class II antibodies, anti-HNA, and HLA class I antibodies with granulocyte agglutination activity.

52
Q

Among blood donors, ___________ have the highest rate of HLA/HNA antibodies

A

Previously pregnant women

Compared with nonpregnant females and males

53
Q

Clinical syndromes associated with platelet alloantigens

A
  • Fetal/neonatal alloimmune thrombocytopenia (FNAIT)
  • Posttransfusion purpura (PTP)
  • Passive alloimmune thrombocytopenia
  • Immune thrombocytopenia after HSCT
  • Occasionally in unresponsiveness to platelet transfusion

Can be an unusual complication of solid organ transplantation in which donor lymphocytes make alloantibodies specific for the platelets produced by the recipient of an organ allograft.

54
Q

A condition similar to alloimmune platelet destruction occurs in patients who lack part or all of a particular platelet GP because of defective alleles of the GP-encoding genes.

A

Platelet Isoantigens

Such patients can make isoantibodies against platelets of virtually all donors that bear the platelet GP.

example is CD36 deficiency

55
Q

___________: Lack CD36 only on their platelets

____________: Lack CD36 only on their platelets, monocytes, and other cells

Platelet GPIV (CD36)

Expressed on various human cells including platelets, macrophages, capillary endothelium, myocytes, and adipocytes

A

Type II deficiency: Lack CD36 only on their platelets

Type I deficiency: Lack CD36 only on their platelets, monocytes, and other cells

56
Q

TRUE OR FALSE

Platelet CD36 deficiency may confer protection from malaria as a receptor for red cells infected with Plasmodium falciparum.

A

TRUE

Platelet CD36 deficiency may confer protection from malaria as a receptor for red cells infected with Plasmodium falciparum.

However, monocyte CD36 deficiency may actually increase the risk for more severe forms of malarial infection because of the lack of clearance of infected cells.

57
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

The only major phase 1 assay remaining in wide use today for platelet antibody detection

A

Serotonin release assay

58
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

Example of phase 2 tests/assays

Detect either surface or total platelet–associated immunoglobulin on patient platelets or on normal platelets after sensitization with patient serum

A

Solid-phase red cell adherence test

Used in platelet crossmatching

59
Q

TESTING FOR PLATELET-SPECIFIC ANTIGENS AND ANTIBODIES

Example of phase 3 tests/assays

A

Monoclonal antibody immobilization of platelet antigens assay and the modified antigen capture ELISA

  • Used to detect alloantibodies in the evaluation of suspected FNAIT and PTP cases as well as autoantibodies in some cases of idiopathic thrombocytopenic purpura
  • Have an advantage over both phase 1 and phase 2 tests in that they detect antibodies that bind to platelet GPs, and not to non–platelet-specific epitopes, such as class I HLA
60
Q

The principal cause of immunologic platelet transfusion refractoriness

A

Antibodies to class I HLA antigens

WILLIAM'S HEMATOLOGY (109 decks)

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