Transfusion medicine

• Type: peptide
• M and N are present on glycophorin A protein, while S, s and U are present on glycophorin B protein
• Glycophorins A and B are encoded by 2 homologous genes, GYPA and GYPB, respectively, both of which are located on chromosome 4
• ~50 antigens in total (Fung: Technical Manual, 19th Edition, 2017)
• Glycophorin molecules contribute to RBC membrane structure with an association to band 3 and likewise act as ligands for Plasmodium falciparum (Fung: Technical Manual, 19th Edition, 2017)
• U is a high frequency antigen found on glycophorin B (Fung: Technical Manual, 19th Edition, 2017)
• Mur antigen is present in ~10% of Chinese and Thai individuals (Fung: Technical Manual, 19th Edition, 2017)
• Mi^a is a low prevalence antigen in the general population (0.01% occurrence) but can be found in certain Asian populations at rates of up to 15% (Reid: The Blood Group Antigen FactsBook, 3rd Edition, 2012)

Race / ethnicity	M+N-	M+N+	M-N+	M-N-	S+s-	S+s+	S-s+	S-s-
White	30%	49%	21%	Rare	10%	42%	48%	Rare
Black (U.S.)	25%	49%	26%	Rare	6%	24%	68%	2%

Adapted from Fung: Technical Manual, 19th Edition, 2017

• Antibodies to M and N are usually cold reactive, not clinically significant and naturally occurring, while S, s and U antibodies are clinically significant
• M antibodies tend to be IgM and are generally not associated with hemolytic disease of the fetus and newborn (HDFN) (rarely reported), though assessment for IgG conversion should be considered (AJP Rep 2017;7:e205)
• N antibodies are generally IgM
• S, s, U and other antibodies tend to be IgG and can cause hemolytic transfusion reactions and HDFN (Fung: Technical Manual, 19th Edition, 2017)
• N antigen exists on the N terminus of the glycophorin A peptide, similar to the N terminus of all glycophorin B peptides; hence, antibodies against N are less common (Fung: Technical Manual, 19th Edition, 2017)
• Mur antibodies are common in Southeast Asia (Fung: Technical Manual, 19th Edition, 2017)
• Mi^a antibodies are clinically significant but reactions are uncommon due to low population prevalence amongst American donors; this may vary based on donor population incidence (Reid: The Blood Group Antigen FactsBook, 3rd Edition, 2012)

A gravida 1 para 0 mother is found to have an anti-M antibody. The clinical team wants to determine if the antibody is IgG or IgM. Treatment of the patient serum with which reagent destroys IgM antibodies and helps to determine if this is an IgG antibody?

1. Addition of antihuman globulin
2. Dithiothreitol (DTT)
3. Enzyme treatment
4. Polyethylene glycol (PEG) enhancement

B. Dithiothreitol (DTT). Dithiothreitol is a reducing agent that destroys the disulfide bonds in IgM antibodies, allowing for identification of underlying antibodies. Answer A is incorrect because while the addition of antihuman globulin and reactivity at 37 °C (indirect antiglobulin test [IAT] / 37 °C phase) may help identify IgG reactivity, this does not destroy the IgM antibodies. Answers C and D are incorrect because enzyme treatment and PEG enhancement likewise do not destroy IgM and may have a variable effect on immunoreactivity.

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Reference: MNSU system

A Jehovah's Witness (JW) patient agrees to receive plasma products only. A type and screen is found to be positive. The patient is disturbed when he sees this result in the patient portal, as he has no transfusion history. What is the best explanation to provide to the patient?

1. He has likely been transfused with red blood cells (RBC) at some point and this is evidence
2. These antibodies can be naturally occurring
3. This is likely passive transfer from his recent fresh frozen plasma (FFP) transfusion
4. This patient needs a RBC transfusion

B. These antibodies can be naturally occurring. Anti-M antibodies often occur naturally, are often IgM and are generally considered clinically insignificant. Answer A is incorrect because outside of an emergent setting, where consent cannot be obtained, patients must consent prior to all blood transfusions. Answer C is incorrect because it is important to note that some JW patients may accept certain blood components, so although it is possible that this patient received FFP, blood donors undergo antibody screening and positive donor units may or may not be transfused. Units may be labeled or discarded if antibodies are identified. Answer D is incorrect becuase nothing suggests that the patient requires a transfusion at this time.

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Reference: MNSU system