Lecture 7_ Chapter Seven Other RBC Grouping Systems (1)

Chapter 7: Other Blood Group Systems

Objectives

• U3L1 – O1: Differentiate clinically insignificant antibodies (reactive in-vitro at IS, IgM class, no hemolysis/decreased RBC survival in-vivo) from clinically significant antibodies (reactive in-vitro at 37°C and/or AHG, IgG class, implicated in HDFN and/or HTR in-vivo).

• U3L1 – O2: Understand the I/i blood group system, its relationship to ABO precursors, and Anti-I and Anti-i antibodies.

• U3L1 – O3: Understand the Lewis system and its antigens and antibodies.

• U3L1 – O4: Understand the MNSs blood system and the antibodies involved.

• U3L1 – O5: Understand the Lutheran blood group system and its antibodies.

• U3L1 – O6: Understand the Kell system and its antibodies.

• U3L1 – O7: Understand the Kidd blood group system and its antibodies.

• U3L1 – O8: Understand the Duffy blood group and its antibodies.

• U3L1 – O9: Distinguish between high-incidence and low-incidence antigens.

• U3L1 – O10: Utilize DTT to distinguish IgM from IgG antibodies and eliminate Kell system antigen activity.

• U3L1 – O11: Understand how enzymes denature blood group antigens or enhance antibody reactivity.

• U3L1 – O12: Understand High Titer Low Avidity (HTLA) antigens.

• U3L1 – O13: Know characteristics of cold and warm antibodies.

• U3L1 – O14: Identify antigens affected by enzymes.

• U3L1 – O15: Understand the concept of dosage in blood group systems.

Blood Group Systems Overview

• ISBT recognizes 47 blood group systems with over 366 antigens; some are rare and disease-associated.

• Importance of ABO and D blood group systems.

• High incidence antigens: present on nearly all individuals.

• Low incidence antigens: present on very few individuals.

• Knowledge of serologic behavior and characteristics of blood group antibodies is critical for identification.

Functional Roles of Blood Group Systems

• Glycosyltransferases: ABO, I, P1PK, Lewis, H blood group systems.

• Structural Relationship: MNS, Diego, Gerbich.

• Transport Proteins: Rh, Kidd, Diego, Colton, Kx.

• Complement Pathway Molecules: Chido/Rodgers, Cromer, Knops.

• Adhesion Molecules: Lutheran, Xg, Landsteiner–Wiener, Indian.

• Microbial Receptors: MNS, Duffy, P, Lewis, Cromer.

• Biologic Receptors: Duffy, Knops, Indian.

Clinically Insignificant vs. Significant Antibodies

Insignificant Antibodies

• Reactive in-vitro at IS.

• Generally of IgM class.

• No hemolysis or decreased RBC survival in-vivo.

Significant Antibodies

• Reactive in-vitro at 37°C and/or by AHG.

• IgG class, implicated in HDFN and HTR.

For Each Blood Group System You Must Know

• Antigen development significance.

• Antibody class typically involved.

• Phase of reactivity in in-vitro tests.

• Clinical significance.

• Donor units: require antigen negativity?

• Unique antigen/antibody characteristics.

Enzymatic Effects on Blood Group Antigens

• Proteolytic Enzymes (e.g., papain, ficin): Remove glycoprotein fragments from RBC membranes, denature certain blood group antigens (e.g., Fya, Fyb).

• DTT (Dithiothreitol): Dissolves disulfide bonds; used to distinguish IgM from IgG and eliminate kell antigen activity.

MNS Blood System (ISBT 002)

• Antigens: M, N, S, s, U.

• Antibodies: M & N (reactive at RT), S & s (clinically significant).

• All show dosage effects; reactions stronger in homozygous individuals.

• Antigens destroyed by enzyme treatments.

Lutheran Blood Group System (ISBT 005)

• Two codominant alleles: Lua, Lub.

• Anti-Lua: Naturally occurring, IgM, reacts at RT, clinically insignificant.

• Anti-Lub: Clinically significant IgG, mild HDFN, and transfusion complications possible. Requires antigen negativity and compatibility for transfusion.

Kell Blood Group System (ISBT 006)

• Key antigens: K (Kell) and k (cellano).

• The K antigen is immunogenic; Anti-K is commonly observed, causing HTRs and HDFN.

• K and k genes are highly significant for transfusions; donors must be antigen negative.

Kidd Blood Group System

• Antigens: Jka and Jkb.

• Clinically significant, responsible for HTR and HDFN.

Duffy Blood Group System

• Antigens: Fya and Fyb, essential for malarial resistance.

• Antigens destroyed enzymatically; clinical significance due to associations with malaria.

U3L1 – O9: Distinguish between high-incidence and low-incidence antigens.

• High-incidence antigens are present on nearly all individuals, leading to a low chance of finding compatible blood for transfusions unless the donor is antigen-negative.

• Low-incidence antigens are found in very few individuals, which may complicate transfusion compatibility and availability.

U3L1 – O10: Utilize DTT to distinguish IgM from IgG antibodies and eliminate Kell system antigen activity.

• DTT (Dithiothreitol) is a reducing agent that dissolves disulfide bonds, allowing for differentiation of antibody classes and inactivation of the Kell system antigens.

U3L1 – O11: Understand how enzymes denature blood group antigens or enhance antibody reactivity.

• Enzymatic treatment can remove glycoprotein fragments and alter antigenic properties, thus affecting the serological reactivity of antibodies during testing.

U3L1 – O12: Understand High Titer Low Avidity (HTLA) antigens.

• HTLA antigens are characterized by a high level of antibodies with weak binding strength (low avidity), affecting transfusion practices due to their potential to misinterpret hemagglutination test results.

U3L1 – O13: Know characteristics of cold and warm antibodies.

• Cold antibodies (usually IgM) react at lower temperatures, whereas warm antibodies (typically IgG) react optimally at body temperature. The distinction is crucial for transfusion management.

U3L1 – O14: Identify antigens affected by enzymes.

• Certain blood group antigens are susceptible to enzymatic degradation, impacting their detection in laboratory tests and leading to variations in antibody reactions.

U3L1 – O15: Understand the concept of dosage in blood group systems.

• Dosage refers to the different strength of reactions based on whether the phenotype is homozygous or heterozygous for a given antigen. Homozygous reactions are generally stronger than those from heterozygous individuals.