MNS Blood System Overview

MNS Blood System

• Antithetical M and N antigens and antithetical S and s antigens exist.
• The U antigen is part of the MNS system, exclusive to some African populations.
• Genetic inheritance of MNS is similar to the Rh system.
• Two pairs of closely linked alleles are responsible for M and N and S and s.
• The GYPA gene controls M and N.
• The GYPB gene controls S and s.
• Glycophorins transverse the red cell membrane and carry M or N and S or s and U.
• M and N antigens have almost equal frequency.
• The frequency of the s antigen is higher than the S antigen.

MNS Antibodies

• Anti-M and anti-N antibodies are often opposite of S, s, and U.
• Anti-M and anti-N antibodies are usually clinically insignificant unless reactive at 37°C.
• Anti-S and anti-s antibodies are not as common as anti-M and anti-N.
• Anti-M antibodies are typically insignificant, but rare cases are linked to severe HDN.
• The effects of anti-M vary based on enzymes, generally decreasing other MNS antigens except U.
• Most anti-M, anti-N, and anti-s antibodies do not bind complement.
• Anti-S antibodies can bind complement sometimes.

Clinical Significance of MNS Antibodies

• Anti-M and anti-N antibodies are relatively common, but transfusion reactions are rare.
• Anti-M and anti-N are seldomly significant clinically, while anti-N is less clinically significant than anti-M.
• Anti-S and anti-s antibodies are relatively uncommon, but transfusion reactions have been reported.
• HDN caused by anti-M and anti-N is rare, while some HDN cases are associated with anti-S and anti-s.
• Some anti-M antibodies react more strongly with M-positive cells at a pH of 6.5.
• Dialysis associated with anti-N antibodies is formed by patients undergoing dialysis on equipment that is sterilized by formaldehyde.
• Some patients form autoantibodies that resemble anti-N serologically.
• The anti-N antibody is often found in people of African ethnicity, but is rare in people of European descent.

P Blood Group System

• Antigens P1 (has both P and P1 on cells), P2 (has only P on cells), and p (has no P or P1) are associated with the P blood group system.
• The P1 antigen has variable strength in individuals with P positive blood, not traditional dosage, and varies per individual.
• The P1 antigen's strength varies greatly among different individuals.
• P1 is often reduced on stored RBCs.
• The expression of antigens in the P blood group system originates from 3 independently inherited genes.
• The P1 antigen forms from the action of adding galactose to precursor chains.
• The GLOB gene converts Pk antigen to P antigen, adding N-acetylgalactosamine to Pk.
• The Pk gene acts by adding galactose to a precursor chain, forming the P antigen.
• Mutations in the Pk gene can result in a p or null phenotype, with no expression of any antigen.

P Phenotypes

• Most individuals have P antibodies (Abs) with poor expression at birth to age 7
• P2 lacks the P1 antigen, expresses Pk, produces anti-P and anti-P1 in plasma.
• P1k lacks the P antigen, expresses P1 and Pk antigen and produces anti-P1 in plasma.
• The P2k phenotype only expresses Pk, produces anti-P and anti-P1 in plasma.
• P is the null phenotype in those that lack P1, P, and Pk antigens and produces anti-P1(anti-PP, Pk [or anti-Tja]) in plasma.

Ab Characteristics

• Anti-P1 is found as a non-red cell immune in 2/3 of P2 individuals.
• Ab formation is rarely stimulated by P1 positive blood transfused to a P2 individual.
• Some anti-P are Donath-Landsteiner antibodies.
• Donath-Landsteiner antibodies are autoantibodies in patients with paroxysmal cold hemoglobinuria (PCH).

P Clinical Significance

• Transfusion reactions are rare in the P blood group system.
• P substances are found in hydatid cyst fluid, worm extracts, and other bodily fluids and substances.
• Compound antibodies can be formed with I blood system antibodies.

Lutheran Blood Group System

• Lua and Lub are codominant alleles in the Lutheran blood group system, with Lu as another amorphic allele.
• Lua and Lub antigens are not fully developed at birth.
• Anti-Lua and anti-Lub antibodies are rare.
• Mild transfusion reactions or HDN, caused by antibodies in the Lutheran blood group system, can sometimes occur.
• The frequency of Lua is low, while Lub has high frequency.
• Some enzymes (2-mercaptoethanol or DTT) reduce Lu antigen activity.

Lutheran Characteristics and Clinical Significance

• Anti-Lua is uncommon, and often not significant, being a naturally-occurring antibody.
• Anti-Lua is typically IgM, though it may sometimes react at room temperature, and best at 37°C.
• Anti-Lua usually does not bind complement.
• Anti-Lub can be IgM, IgG, or IgA and reacts best at 37°C.
• Anti-Lua is a rare antibody.
• Antibodies don't cause HDN or transfusion reactions even if present in IgG form.
• Anti-Lub can cause transfusion reactions.
• Finding Lu-negative RBCs is difficult.

Xg Blood System

• The Xg gene is carried on the X chromosome.
• The Xg antigens are present in approximately 66% of males and 90% of females.
• Xg antibodies are typically insignificant
• Antibodies are present in the blood system.
• Antigens are Xga.

Xg Blood System Inheritance

• A male with Xga and a female with Xg mating results in several possible offspring phenotypes.
• Daughters can have the Xg(a) positive phenotype, while sons have the Xg(a) negative phenotype
• Males are hemizygotes for the Xg gene since they only have one X chromosome.

Xg Antibodies

• Xg antibodies are usually red cell immune.
• Most Xg antibodies bind complement.
• Xg antibodies are typically detected using an AHG test.
• Xg antibodies are found at birth, though cause no HDN or transfusion reactions.

High Incidence Antigens

• Antibodies against these antigens are very uncommon, causing significant difficulties in finding compatible blood units.
• Antigens, including Cellano (k), Colton (Coa), Cartwright (Yta), Vel (V), Gerbich (Ge), and Sid (Sda), are found in over 90% of the European population.

Low Incidence Antigens

• Low-incidence antigens are found at a rate less than 1/1000.
• These antigens include Levy, Wright (Wra), and Swann (Swa).
• Antibodies against low-incidence antigens often cause little difficulty when attempting to perform crossmatching.

High Titre Low Avidity Antibody (HTLA)

• HTLA antibodies react weakly and inconsistently in AHG tests, though remain present even at low concentrations.
• This antibody's reactions remain inconsistent, even when titrated to very low concentrations.
• HTLA antibodies are neutralized by group-specific substances (GSS).
• HTLA antibodies rarely cause HDN or transfusion reactions..
• These antibodies may be associated with white blood cell (WBC) antibodies.
• Examples include Cost-Sterlin (Csa), York (Yka), and Gregory (Gya).

HLA Antibodies

• Antibodies targeting white blood cell (WBC) antigens are found in plasma, especially in patients with multiple transfusions or multiple pregnancies.
• HLA antibodies can bind complement, detectable by AHG.
• Antibody analyses often produce non-specific results.
• Common WBC antibodies are anti-Bga and anti-Bgb.
• Severe transfusion reactions may be caused by HLA antibodies.
• Symptoms may include fever and respiratory distress.
• Compatibility is very important in organ donations.

GPI-Linked Glycoprotein Antigens

• Rare RBC membrane protein defects cause acquired hemolytic anemia (PNH), and linked to GPI.
• These defects lack GPI-linked glycoproteins.
• RBCs with this defect don't express antigens that are present on GPI-linked glycoproteins.
• Examples of antigens include JMH, Cartwright (Yt), Dombrock (Do), and Cromer (Cr).

Distinguishing Facts

• Chido/Rogers soluble antigens are located on C4 complement components present in plasma and absorbed onto RBCs after birth.
• Plasma neutralization can help identify specific antibodies.
• Chloroquine diphosphate or EDTA/glycine acid can dissociate IgG antibodies bound to RBCs.
• Sda antigen variability exists amongst people and is weak in pregnancy.
• The Sda antigen is found in urine.
• In some ethnic backgrounds, the Sda antigen is more frequent, but typically not clinically significant.
• Some background information may be found in course notes.

Explore the intricacies of the MNS blood system, including the role of M and N antigens as well as S and s antigens. Learn about their genetic inheritance and the implications of various antibodies associated with this blood group system. This quiz provides valuable insights into the complexities of blood group genetics and clinical significance.