System Discovery / Genes Antigens / Epitopes (where found / Phenotypes / Enumerated Antibodies / Enumerated Clinical notes / Distinguishing features

unique features) variants

A. ABO & H Discovered by Karl Landsteiner A, B, H — carbohydrate epitopes on 1. A, B, AB, O (classic) 1. Naturally occurring (IgM): • Most important in transfusion &
(1900). glycoproteins & glycolipids Anti-A, Anti-B (major transplantation.
2. Weak: A1, A23. Null: (1)
transfusion risk)
Genes on 9q34 (ABO); H/Se loci on Expressed on RBCs, platelets, Bombay (Oh), (2) para- • Distinguishing: A1 vs A2 — A1 agglutinates
other chromosomes. endothelial cells, secretions in Bombay 2. Less common: Anti-A1, Anti- with Dolichos Biflorus (lectin).
secretors. H (see cell)
• Bombay (Oh): no H → cannot receive O
blood; serologically appears as O but has
anti-H.

• ABO Abs are room-temperature, saline

agglutinins; cause acute HTR, HDFN, Organ
rejection.

B. MNS Landsteiner & Levine (M/N 1927; S • M, N (GYPA) — major 1. M/N types (M+N−, M−N+, 1. Anti-M (usually IgM, cold- • M/N: defined by amino-acid differences (M
1947; s 1951). sialoglycoprotein M+N+) reactive) = Ser¹, Gly⁵; N = Leu¹, Glu⁵).
• S, s, U (GYPB)
Genes: GYPA (M/N), GYPB (S/s/U). 2. S/s types (S+s−, S−s+) 2. Anti-N (IgM; uncommon; • S/s: difference at aa29 (S = Met, s = Thr).
• Epitopes on RBC membrane
glycoproteins Anti-Nf in dialysis exposure)
3. Rare: U−, En(a−), Mk • U antigen: high prevalence in S+ or s+
• Many antigens (>46). (complete loss) 3. Anti-S, Anti-s (IgG, clinically individuals — important in Black
significant) populations. U− phenotype → severe
transfusion challenge and HDFN.
4. Anti-U (IgG; severe)

C. P (P1Pk / P) Landsteiner & Levine (1927) P1, P, Pk — glycosphingolipid 1. P1 (P1+P), P2 (P only) — 1. Anti-P1 (IgM, naturally • Donath-Landsteiner antibody (auto-anti-
(globoside) >99% donors are P1 or P2 occurring; neutralizable by P) → Paroxysmal Cold Hemoglobinuria
ISTB: P (Globoside) & P1/Pk group.
hydatid fluid) (PCH) (biphasic hemolysin).
Epitopes found on RBCs and in 2. Null: p phenotype (lacks P
Genes: P1Pk (22q13.2), P (15q11–
secretions (Plasma, Hydatid cyst fluid). antigens), Pk phenotype 2. Alloanti-PP1Pk (anti-Tja): IgM • p phenotype resistant to parvovirus B19.
q13).
± IgG3 (mixture anti-P/anti-
• Anti-PP1Pk in p individuals reacts with all
P1/anti-Pk)
RBCs except p.
3. Alloanti-P (IgM, weak)

4. Auto-anti-P (Donath-
Landsteiner, IgG; biphasic
hemolysin)
D. Rh & RhAG Landsteiner & Wiener (1940). Genes: D, C, c, E, e — protein epitopes on 1. D+ or D− (Rh 1. Anti-D (most immunogenic, • Anti-D is the most clinically important —
RHD, RHCE (Chr 1); RHAG required RhD/RhCE complexes on RBC positive/negative) IgG) causes severe HDFN and HTR;
for Rh protein expression. membrane; RhAg (Rh-associated
2. Weak D (reduced 2. Anti-c, Anti-E, Anti-C, Anti-e RhIg (RhoGAM) prophylaxis prevents
glycoprotein) supports expression.
expression) (IgG) sensitization.

3. Partial D (missing epitopes) • Rhnull → hemolytic anemia,

stomatocytosis;
4. Rhnull (no Rh proteins)
Rh alloantibodies may be complex
(compound specificities: anti-ce, anti-Ce,
anti-cE, anti-CE).

E. Lutheran (Lu) Lutheran system — 19 antigens; Lua, Lub — protein epitopes on 1. Lua+, Lub+ combinations; 1. Anti-Lua, Anti-Lub (usually • Generally not clinically significant; rarely
appears at Orthochromatic Lutheran glycoprotein. null rare IgG, often clinically mild) causes HDFN/HTR.
Erythroblast stage.
• Increased Lutheran expression on
Reticulocytes/Sickle cells may play a role in
vaso-occlusive pathology.

F. Kell & Kx Kell system (K, k etc.); Kx protein Kell antigens (K, k, Kp, Js) on Kell 1. Kell antigen variations (K/k 1. Anti-K (IgG, highly clinically • Anti-Kell causes severe HDFN often with
related (Xk gene). glycoprotein; Kx on Kx protein polymorphism) significant)2. Other anti-Kell Reticulocytopenia rather than
specificities (IgG)= hyperbilirubinemia.
Epitopes on RBC membrane proteins. 2. McLeod phenotype:
absence of Kx protein (Xk • McLeod syndrome (Kx absent) →
defect) acanthocytes, shortened RBC survival,
neurologic/ muscular abnormalities (late
onset).

G. Lewis (Le) Lewis antigens synthesized in GIT Lea, Leb — fucosylated carbohydrate 1. Le(a+b−) — non-secretor 1. Anti-Leᵃ, Anti-Leᵇ (IgM, • Le(a+b+) is transient/rare (seen in infants
(FUT3) and adsorbed onto RBCs epitopes, not intrinsic to RBCs usually clinically insignificant) while antigen expression matures).
2. Le(a−b+) — secretor (Leᵇ
(adsorbed from plasma/secretions).
Dependent on Se (FUT2) secretor forms) • Lewis phenotype influenced by FUT2
status. (secretor) & FUT3 (Le) interplay — secretors
3. Le(a−b−) — Lewis null /
convert Leᵃ → Leᵇ in secretions so RBCs
non-secretor or Le gene null
normally show either Leᵃ or Leᵇ, not both.

• Clinical associations: H. pylori binds

Le/H/Ley epitopes; non-secretor phenotype
confers some protection vs norovirus
 • Lewis null linked with increased Candida
vaginitis and UTI.

H. Duffy (Fy) Duffy antigens (Fya/Fyb) — encoded Fya, Fyb, Fy3, Fy5, Fy6 — 1. Fy(a+b−)2. Fy(a−b+)3. 1. Anti-Fya, Anti-Fyb (usually • Duffy null (Fy[a−b−]) confers resistance to
by FY gene. protein/carbohydrate epitopes; Fy(a+b+)4. Fy(a−b−) — IgG, clinically significant) Plasmodium vivax invasion — strong racial/
common in many Africans geographic distribution.
Expressed on RBCs and many tissues
(Duffy null)
(e.g., renal endothelium, lung • Anti-Duffy can cause HTR and HDFN;
epithelium, cerebellar Purkinje cells). detectable in IAT at 37°C.

I. Kidd (Jk) Kidd antigens encoded by SLC14A1 Jka, Jkb — protein epitopes (urea 1. Jk(a+b−) 1. Anti-Jka, Anti-Jkb (IgG1/IgG3; • Associated with delayed hemolytic
urea transporter gene. transporter) on RBC membrane. often transient and can drop to transfusion reactions (DHTR) — antibodies
2. Jk(a−b+)
undetectable levels) often disappear and then cause anamnestic
3. Jk(a+b+) responses on re-exposure.

4. Jk(a−b−) (rare/null) • Anti-Jk can be hard to detect in routine

screening.

J. Diego (Di / Wr) Diego antigens on AE1 (band 3) anion Diᵃ, Diᵇ; Wrᵃ, Wrᵇ; other low-incidence 1. Di(a+b−) etc.; Diᵃ frequency 1. Anti-Diᵃ, Anti-Diᵇ, Anti-Wrᵇ • Diᵃ is population-specific and important in
exchanger; antigens. varies by ancestry (higher in (IgG; red-cell stimulated; IAT anthropologic genetics.
Mongolian/Native American reactive)
Diᵃ useful in anthropologic studies Epitopes on band 3 protein. • Anti-Diego antibodies can cause HTR and
groups)
(Mongoloid ancestry). HDFN.

K. Yt Antigens on erythrocyte Ytᵃ (high incidence, ~99.8%) 1. Yt(a+b−)2. Yt(a+b+) 1. Anti-Ytᵃ, Anti-Ytᵇ (IgG, IAT • Antigens are on AChE — unusual
(Cartwright) acetylcholinesterase (AChE). reactive) enzymatic carrier.
Ytᵇ (low incidence, ~8%).
• Antibodies are clinically important
(transfusion implications).

L. Xg X-linked; gene on short arm of X Xgᵃ — protein epitope with cell- 1. Female: ~89% Xgᵃ positive 1. Anti-Xgᵃ (IgG, usually red-cell • Xg is sex-linked—useful in red cell genetic
chromosome; adhesion properties related to CD99. stimulated) studies and chimerism investigations.
2. Male: ~66% Xgᵃ positive
Xgᵃ homology with CD99. (sex differences due to X • Anti-Xgᵃ rarely causes HTR/HDFN.
linkage)

M. Scianna (Sc) Antigens on ERMAP (erythrocyte Sc1, Sc2, Sc3 — epitopes on ERMAP 1. Sc1/Sc2/Sc3 genotype 1. Anti-Sc1, Anti-Sc2 (IgG, red- • Scianna antibodies generally mild; anti-
membrane associated protein). glycoprotein. variants; Sc2 rare (↑ in cell stimulated, usually mild)2. Sc3 has been linked to mild HTR.
Mennonite population) Anti-Sc3 (IgG; can cause mild
transfusion reactions)
 • Anti-Scianna can be neutralized with
recombinant ERMAP protein (useful
diagnostically).

N. Dombrock Contains ~10 antigens; autosomal Doᵃ, Doᵇ, Gyᵃ, Hy, Joᵃ — epitopes 1. Doa/ Dob major alleles; 1. Mostly IgG antibodies, often • Antibodies may cause delayed HTRs but
(Do) codominant. encoded on DO gene cluster. Donull (Gy(a−)) is rare weak or masked; many not HDFN.
(recessive, sometimes destroyed by DTT/AET.
• Serology tricky (weak reactions,
acquired in PNH).
enzyme/DTT sensitivity).

O. Colton (Co) Antigens carried on aquaporin-1 Coᵃ (high incidence), Coᵇ, Co3 — 1. Co(a+b−), Co(a−b+) 1. Anti-Coᵃ, Anti-Coᵇ (IgG) • Null (Co[a−b−]) impairs RBC water
(AQP1) water channel encoded by epitopes on AQP1. permeability but generally not systemic
2. Null: Co(a−b−) rare
AQP1 (Chr 7). disease.

• Antibodies may cause mild–moderate HTR

and mild HDFN.

P. LW (ICAM-4 / Antigens associated with Rh proteins; Lwᵃ, Lwᵇ — epitopes on ICAM-4 (linked 1. Neonates: strong Lw 1. Anti-Lw (IgG; sometimes • Lw antigen expression is enhanced by
Landsteiner- ICAM-4 gene (Chr 19). to Rh complex). expression naturally occurring) RhD presence.
Wiener)
2. Adults: often weaker • Anti-Lw rarely causes HTR/HDFN;
expression important in certain serologic puzzles.

Q. Chido / Antigens are complement C4d Ch1–Ch6, Rg1, Rg2 — epitopes derived 1. Serologic patterns depend 1. IgG antibodies that are often • Antibodies often interfere with serologic
Rogers (Ch/Rg) fragments bound to RBC membrane from complement (C4d) associated on complement deposition; clinically insignificant and tests (complement interference), but rarely
(C4A/C4B genes, Chr 6). with RBC membrane. neutralized by plasma neutralized by plasma cause HTR/HDFN.

• Important to recognize to avoid

misinterpreting crossmatches.

R. Gerbich (Ge) Antigens on glycophorin C/D Ge2, Ge3, Ge4 — sialoglycoprotein 1. Common phenotypes 1. Anti-Ge (IgG) • Gerbich null (loss of glycophorin C/D) may
encoded by GYPC (Chr 2). epitopes on RBC membrane. expressing Ge antigens confer some resistance to P. falciparum
invasion.
2. Null: Ge:–2,3,4 (rare)
• Antibodies can cause mild HTR and
variable HDFN severity.

S. Cromer Antigens on decay-accelerating >20 high-incidence antigens (e.g., Cra) 1. Normal expression 1. Anti-Cromer (IgG) • Inab phenotype (CD55 deficiency)
factor (DAF / CD55) (Chr 1). on CD55 (GPI-anchored). increases susceptibility to complement-
2. Null: Inab (Cromer-null,
mediated lysis; links to PNH noted.
CD55 deficiency)
 • Antibodies cause transfusion issues but
usually not HDFN (fetal expression low).

T. Knops Antigens on complement receptor 1 Kn(a), Kn(b), McC(a), Sl(a), Yk(a) — 1. Highly polymorphic alleles; 1. Usually IgG; often clinically • Knops polymorphisms may influence
(CR1) (Chr 1). epitopes on CR1 (involved in immune population variation insignificant malaria susceptibility and immune
complex clearance). complex handling. Serologic reactions are
often weak.

U. Indian (In) Antigens on CD44 (Chr 11), an Ina (rare), Inb (common) — CD44 1. In(a+b−), In(a−b+); Null: 1. Anti-Ina (IgG; can be • Anti-Ina can cause mild HTRs but usually
adhesion glycoprotein. epitopes on RBCs. In(a−b−) rare clinically significant) not HDFN.

• CD44 has broader roles in

inflammation/cancer; RBC expression
limited.

V. I (I/i) Developmental antigen system: linear i (linear precursor) vs I (branched) — 1. Newborns/young infants: i 1. Auto-anti-I (IgM, common • Auto-anti-I is a cold agglutinin (may bind
i in newborns → branched I in adults carbohydrate epitopes on RBC dominant cold-reactive autoantibody)2. complement); usually clinically insignificant
(branching glycan change ~18 glycans. Allo-anti-I rare unless active at 37°C.
2. Adults: I dominant
months).
(conversion by ~18 months) • Prewarming or enzyme methods used to
avoid interference in testing.

W. Gil (Colton Colton system (AQP1) described Gil / Colton antigens on aquaporin 1. Present/absent variants 1. Anti-Gil / Anti-Colton (IgG; • Anti-Colton (Gil) may cause HDFN and
related note) earlier; Gil entry refers to aquaporin- family (AQP1) — epitopes on RBC (Co(a/b) etc.) rare) HTR.
linked antigenic effects on RBCs and membrane & renal tubules.
• Aquaporin role in water transport / urine
kidney tubules.
concentration — absence typically not
systemic but affects RBC water
permeability.

✓ Severe HDFN: Rh (especially D), Kell, Duffy, Kidd, MNS (S, s, U), Diego
✓ Acute HTR: ABO (most dangerous), Rh, Kell
✓ Delayed HTR (amnestic): Kidd (classic), Duffy, Kell, Rh, Dombrock
✓ Cold-reactive / Autoantibody issues: I (Cold agglutinin), P (Donath-Landsteiner)
✓ Rare transfusion challenges: Bombay (Oh, anti-H), U– (MNS), Duffy null, McLeod (Kx), Diego (Diᵃ)
ABO & H Gastric carcinoma (↑ A) · Peptic ulcer (↑ O) · Thrombosis & CVD (↑ non-O; ↑ vWF & factor VIII) · Malaria (O protective vs P. falciparum) · Bombay phenotype → transfusion issues

MNS Malaria invasion pathways (glycophorin A/B) · En(a–) linked to hereditary elliptocytosis

P (P1Pk) Hydatid disease (Echinococcus) · Paroxysmal Cold Hemoglobinuria (auto-anti-P) · Parvovirus B19 resistance (p phenotype)

Rh Hemolytic disease of newborn (classic RhD) · Rhnull → chronic hemolytic anemia, stomatocytosis

Lutheran Enhanced expression in sickle cell reticulocytes → vaso-occlusion contribution

Kell / Kx McLeod phenotype → neuromuscular disorder, cardiomyopathy, acanthocytosis · CGD (X-linked; Kx deficiency)

Lewis H. pylori binding (Leᵇ) → gastric cancer risk · Norovirus binding (secretor + Leᵇ) · Le(a–b–) → ↑ Candida vaginitis & UTI

Duffy (Fy) Fy(a–b–) → resistance to P. vivax & P. knowlesi malaria · DARC → inflammation, HIV progression

Kidd (Jk) Jk-null → resistance to 2M urea lysis · Defective renal concentrating ability (urea transport)

Diego (Di) Marker in Mongoloid ancestry · Band 3 mutations → hereditary spherocytosis, SE Asian ovalocytosis

Yt (Cartwright) Acetylcholinesterase carrier (limited direct disease association)

Xg Genetic marker for X-linked anomalies · Chimerism & sexing studies

Scianna (Sc) Sc2 enriched in Mennonite population (anthropologic link)

Dombrock (Do) Antigens lost in PNH (Donull phenotype)

Colton (Co) Aquaporin-1 deficiency → impaired water permeability, renal concentrating defect

LW (ICAM-4) Malaria cytoadherence · Role in erythropoiesis (integrin binding)

Chido/Rodgers (Ch/Rg) Complement C4 fragments → autoimmune disease link

Gerbich (Ge) Ge– → resistance to P. falciparum malaria · Glycophorin C mutations → hereditary elliptocytosis

Cromer (Cr) Inab phenotype (CD55 deficiency) → complement-mediated lysis, PNH-like states

Knops (Kn) CR1 polymorphisms → malaria severity, SLE (low CR1 expression)

Indian (In) CD44 → cancer invasion & metastasis

I (I/i) Auto-anti-I → Cold Agglutinin Disease, Mycoplasma pneumoniae infection · i persistence → congenital cataracts, leukemia

Gil / Colton-related Aquaporin-linked → renal tubular concentrating defect