Table of Contents
CD10 | CD11 | CD11a | CD11b | CD11c | CD11d | CDw12 | CD13 | CD14 | CD15 | CD15s | CD15u | CD16 / CD16a | CD16b | CD17 / CDw17 | CD18 | CD19 | Diagrams / tables | Microscopic (histologic) imagesCite this page: Pernick N. CD10-19. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd10to19.html. Accessed December 26th, 2024.
CD10
- See CD10
CD11
- Alpha component of various integrins (CD11a, CD11b, CD11c, CD11d)
- Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain
- Adhesion molecules of the beta2 integrin family (CD11 / CD18) plays an essential role in neutrophil recruitment and activation during inflammation
- Clinical features: deficiency of CD18 component (leukocyte adhesion deficiency) is a rare, inherited disorder, causing recurrent severe bacterial infections early in life, possibly fatal (OMIM: 116920 [Accessed 10 May 2021], Hematol Oncol Clin North Am 1988;2:13)
CD11a
- Alpha integrin chain at 16p11-13.1 that binds to CD18 and has various leukocyte functions (OMIM: 153370 [Accessed 10 May 2021])
- Also called integrin alpha L, ITGAL and LFA1 alpha chain (in complex with CD18)
- Pathophysiology:
- Alpha integrin chain which binds to CD18 and mediates leukocyte adhesion to endothelium, leukocyte trafficking through activated endothelium, lymphocyte blastogenesis, lymphocyte endothelial cell adhesion, lymphocyte recirculation through lymph nodes, cytotoxic T cell mediated killing and antibody dependent killing by neutrophils and monocytes
- Also mediates binding to unopsonized bacteria (e.g. E. coli) and fungi (e.g. Histoplasma capsulatum)
- With CD18, binds to ICAM1 (CD54), ICAM2 (CD102), ICAM3 (CD50) and ICAM4 (CD242)
- CD11a identifies effector and memory CD8+ T cells, independent of antigen specificity (Oncoimmunology 2013;2:e23972)
- Decreased levels in CD4+ T cells in infants with biliary atresia, due to hypermethylation of CD11a promoter region (Biochem Biophys Res Commun 2012;417:986)
- Increased levels in CD4+ T cells with immune thrombocytopenia (ITP) (J Clin Immunol 2011;31:632)
- Clinical features:
- Anti CD11a antibody therapy (efalizumab):
- Improves moderate / severe plaque psoriasis (J Cutan Med Surg 2003;7:198, Arch Dermatol 2002;138:591)
- Although may cause progressive multifocal leukoencephalopathy (Neurology 2012;78:458)
- Treatment of macular edema (Invest Ophthalmol Vis Sci 2011;52:6919)
- Treatment of moderate to severe Crohn disease (Dig Dis Sci 2011;56:1806)
- Phase I / II trials pending for immunosuppression in renal transplants (Am J Transplant 2007;7:1770)
- May act by promoting naïve T cell anergy (J Invest Dermatol 2008;128:2615)
- Improves moderate / severe plaque psoriasis (J Cutan Med Surg 2003;7:198, Arch Dermatol 2002;138:591)
- Uses by pathologists:
- CD11a deficiency during flow cytometry useful to diagnose acute promyelocytic leukemia (Am J Clin Pathol 2012;138:744)
- CD11a deficiency during flow cytometry useful to diagnose AML M7, Down syndrome related AML and transient myeloproliferative disease in children with and without Down syndrome (Cytometry B Clin Cytom 2013;84:370)
- Positive staining - normal: all leukocytes
- Positive staining - disease: acute promyelocytic leukemia post treatment (treatment induces expression (Leuk Res 2008;32:315)
- Negative staining: platelets, various intermediate and high grade lymphomas
- Anti CD11a antibody therapy (efalizumab):
CD11b
- Alpha component of an integrin at 16p11-13.1 that mediates adhesion (OMIM: 120980 [Accessed 10 May 2021])
- Also called integrin alpha M, Mac1 and CR3A
- Pathophysiology:
- Mediates monocyte / macrophage / granulocyte adhesion to substrates by opsonization with iC3b, leading to phagocytosis, neutrophil aggregation and chemotaxis
- Ligands include fibrinogen, Factor X, ICAM1, iC3b, Saccharomyces cerevisiae, Staphylococcus epidermidis and Histoplasma capsulatum
- Expression is associated with activation of T cells
- Clinical features:
- Gr1+ CD11b+ myeloid cells promote metastasis (Cancer Cell 2008;13:23)
- Poor prognostic factor in preB acute lymphoblastic leukemia, cytogenetically unfavorable AML (Blood 2010;115:3763, Leuk Res 2013;37:122)
- Documents maturation of tumor cells in acute promyelocytic leukemia patients receiving all trans retinoic acid therapy (cells become CD11b+, CD16+) or arsenic trioxide (CD11b+, CD33+) (Arch Pathol Lab Med 2003;127:e4, Mod Pathol 2000;13:954)
- Histoplasma capsulatum causes decreased cell surface CD11b expression and an antiapoptotic state on leukocytes (Scand J Immunol 2002;56:392)
- May be useful to diagnose aspirin induced asthma, due to upregulation of CD11b on eosinophils (Allergol Int 2013;62:367)
- rs1143679 variant is associated with systemic lupus erythematosus and impairs:
- CR3 monocyte functions (Ann Rheum Dis 2012;71:2028)
- Neutrophil functions (Arthritis Rheum 2013;65:2907)
- In Type 2 diabetes, hyperglycemia leads to increased CD11b on granulocytes and monocytes, exacerbating their inflammatory status (J Investig Med 2013;61:972)
- Uses by pathologists:
- Common myeloid marker and NK (natural killer cell) antigen
- Differentiates recovery from acute agranulocytosis (CD11b+, CD117-) from acute promyelocytic leukemia (CD11b-, CD117+) (Am J Clin Pathol 2002;118:31)
- Differentiates Down syndrome patients with AML (usually CD13+, CD11b+) from transient myeloproliferative disorder (usually CD13-, CD11b-) (Am J Clin Pathol 2001;116:204)
- May be useful for flow cytometry diagnosis of myelodysplastic syndrome as part of panel (Ann Clin Lab Sci 2012;42:271)
- Positive staining - normal:
- Granulocytes, macrophages
- Follicular dendritic cells, myeloid cells beginning with promyelocytes, NK cells, some B / T cells
- Positive staining - disease:
- Hairy cell leukemia (virtually all)
- Also acute myelogenous leukemia, lymphoma (various), sinus histiocytosis with massive lymphadenopathy (Am J Clin Pathol 2008;129:934, Hum Pathol 1992;23:647)
- Negative staining: Gaucher cells (Am J Clin Pathol 2004;122:359)
CD11c
- Integrin at 16p11-13.1 that acts as a fibrinogen receptor and is important in monocyte adhesion and chemotaxis (OMIM: 151510 [Accessed 10 May 2021])
- Also called integrin alpha X, CR4 and LeuM5
- Pathophysiology:
- Clears opsonized particles and immune complexes
- Also binds to fibrinogen and is involved in adhesion of monocytes and neutrophils to endothelium and chemotaxis
- CD11c+ CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity (Diabetes 2010;59:1648)
- Clinical features:
- Associated with good prognosis in B-CLL
- High expression in polycystic ovary syndrome (Eur J Endocrinol 2012;167:705)
- Uses by pathologists: marker of histiocytes, NK cells; used to diagnose hairy cell leukemia (with other markers)
- Positive staining - normal:
- Granulocytes, macrophages, NK cells, dendritic cells (PLoS One 2012;7:e33556)
- 50% of activated CD4 / CD8+ T cells
- Positive staining - disease:
- Hairy cell leukemia (classic and variant) (Am J Clin Pathol 1991;96:100)
- AML M4 and M5 (50%), follicular lymphoma (some), Langerhans cell histiocytosis, lymphoplasmacytic lymphoma (81%) (Am J Clin Pathol 2005;124:414)
- Psoriatic skin lesions (Proc Natl Acad Sci USA 2005;102:19057)
- Sinus histiocytosis with massive lymphadenopathy (Hum Pathol 1992;23:647)
- Small lymphocytic lymphoma (Am J Clin Pathol 1998;110:582)
- Splenic lymphoma with villous lymphocytes (Am J Clin Pathol 1988;90:250)
- Negative staining:
- Mantle cell lymphoma (Am J Clin Pathol 2010;134:271)
- AML M3 (Am J Clin Pathol 1998;109:211)
- Splenic and nonsplenic marginal zone lymphoma (Am J Clin Pathol 1996;105:277)
CD11d
- Receptor for ICAM3 (CD50) and VCAM1 (CD106) at 16p11.2 (OMIM: 602453 [Accessed 10 May 2021])
- Also called integrin alpha D
- No significant clinical use by pathologists
- Positive staining - not malignant: macrophage foam cells within atherosclerotic plaques
- Negative staining: B cells, follicular dendritic cells
CDw12
- Has been deleted
- In mice, includes Wdr59 antibody
- Only 4 PubMed citations, most recently in 1998 (Leuk Res 1998;22:537)
- No significant clinical use by pathologists
- Positive staining - normal: granulocytes, monocytes, NK cells and platelets
- Negative staining: basophils, bone marrow precursors and AML
- References: Blood 1987;70:1872, Blood 1990;75:198, Folia Biol (Praha) 1993;39:124, GeneCards: CDW12 [Accessed 10 May 2021]
CD13
- See CD13
CD14
- Pattern recognition receptor that detects antigenic molecules on the surface of various microorganisms
- Also called lipopolysaccharide (LPS) receptor, monocyte differentiation antigen
- Mutations can prevent adequate inflammatory response to infection, leading to systemic infections
- Pathophysiology:
- GPI linked pattern recognition receptor that detects antigenic molecules on the surface of bacteria (lipoteichoic acid on gram positive, lipopolysaccharides on gram negative), myobacteria (glycolipids) and fungi (mannans), as part of the innate (nonadaptive) immune system (adaptive immune system refers to lymphocytes recognizing microorganism proteins via T cell receptors and antibodies) (Wikipedia: Innate Immune System [Accessed 10 May 2021]
- Soluble form of CD14 is secreted by liver and monocytes; in low concentrations it confers LPS responsiveness to cells which are otherwise CD14 negative
- Macrophages with a multiprotein complex of CD14, MD2 and TLR4 bind to LPS, causing macrophage activation and release of cytokines (Mol Immunol 2014;57:210)
- Overstimulation may cause toxic shock syndrome (Nature 1998;392:505)
- Detection of lipopolysaccharide induces IL12 production (mediated by CD14), producing interferon gamma, which steers immune system away from allergy driven Th2 phenotype, associated with IgE production
- Important for clearance of apoptotic cells (Nature 1998;392:505, PLoS One 2013;8:e70691)
- Early promonocytes express MY4 epitope; mature monocytes express MO2 epitope; neoplastic monocytes also often express MY4 but not MO2 (Am J Clin Pathol 2005;124:930)
- Clinical features:
- May regulate gastric cancer cell epithelial-mesenchymal transition and invasion (Oncol Rep 2013;30:2725)
- CD14-159C/T polymorphism:
- Contributes to TB susceptibility, particularly in Asians (Int J Tuberc Lung Dis 2013;17:1472)
- May be risk factor for chronic lung disease in India (Indian J Hum Genet 2013;19:188)
- Uses by pathologists: identify mature monocytes / macrophages
- Positive staining - normal: macrophages / monocytes (90%), Langerhans cells, dendritic cells, B cells and granulocytes (weak, 30%)
- Positive staining - disease: AML M4 / M5 (50 - 90%), chronic myelomonocytic leukemia and histiocytic sarcoma (Am J Clin Pathol 2011;135:720)
- Negative staining:
- Myeloid progenitors, AML M0 - M2 (usually), M3, M6 and M7
- Sinusoidal histiocytes with phagocytic properties (erythrophagocytosis, anthracosis, tingible body macrophages) (Hum Pathol 2006;37:68)
- Gaucher macrophages (Hum Pathol 1992;23:1410)
- Most epithelial and endothelial cells
- Reference: OMIM: 158120 [Accessed 10 May 2021]
CD15
- See CD15
CD15s
- Biochemically similar to CD15 but with different functions
- Also known as sialyl Lewis X
- Important in leukocyte tethering and rolling (Wikipedia: Sialyl LewisX [Accessed 10 May 2021])
- Clinical features:
- May be associated with refractory Hodgkin lymphoma (J Cancer 2012;3:322)
- Deficiency causes Rambam-Hasharon syndrome (OMIM: 266265 [Accessed 10 May 2021])
- Also called leukocyte adhesion deficiency 2 (eMedicine: Leukocyte Adhesion Deficiency [Accessed 10 May 2021])
- Expression is correlated with susceptibility to human granulocytic ehrlichiosis (J Clin Invest 1999;103:407)
- Elevated serum levels in hospitalized infants with serious bacterial infections (Eur J Pediatr 2013;172:1363
- Exhibits reversed cell polarity in invasive micropapillary carcinoma of breast (Int J Surg Pathol 2010;18:193)
- Pathophysiology:
- Differs from CD15 by addition of a sialic acid; myeloid maturation is accompanied by relative loss of CD15s and gain of CD15 expression (Nat Chem Biol 2008;4:751)
- Mediates leukocyte rolling (Proc Natl Acad Sci USA 1997;94:3172)
- Ligand (receptor) for CD62P and CD62E
- May play a role in cluster formation in lymphoid follicles (Immunol Lett 2001;79:181)
- No significant clinical use by pathologists
- Positive staining - normal: granulocytes, macrophages; also some T cells, B cells and NK cells
- Positive staining - disease:
- Cirrhosis, metastatic carcinoma, fibrolamellar and other hepatocellular carcinoma (Arch Pathol Lab Med 1992;116:643)
- CD4+ CD56+ neoplasia (Leuk Lymphoma 2003;44:281)
- Sezary syndrome (J Am Acad Dermatol 2001;44:456)
- Negative staining: normal hepatocytes
CD15u
- Adhesion protein representing the sulfated form of CD15
- Also called sialyl 6-sulfo Lewis
- Major L selectin ligand on high endothelial venules of human peripheral lymph nodes (Biochem Biophys Res Commun 2000;278:90)
- No significant clinical use by pathologists
- Positive staining - normal:
- Neutrophils, basophils, mature granulocytes, monocytes, NK cells and T lymphocytes
- Also immature bone marrow cells, endothelial cells of high endothelium (HEV) of peripheral lymph nodes
- Expression on lymphocytes is variable depending on the antibodies used for detection
- Positive staining - disease: myelomonocytic leukemia cells, adenocarcinoma
CD16 / CD16a
- CD16 has been identified as IgG, Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction
- Also known as Fc gamma receptor III A, FCGR3A, low affinity immunoglobulin gamma Fc region receptor III A
- CD14+ CD16+ monocytes have increased capacity to produce proinflammatory cytokines such as TNF alpha and are elevated in various inflammatory diseases, including coronary artery disease (Thromb Haemost 2004;92:419)
- CD16a polymorphisms influence:
- Severity but not the incidence of IgA nephropathy in Japanese patients (Nephrol Dial Transplant 2005;20:2439)
- Pathogenesis of coronary artery disease (Atherosclerosis 2005;180:277)
- Clinical response to rituximab and infliximab for Crohn disease (DNA Cell Biol 2012;31:1671, Br J Haematol 2011;154:223, Immunogenetics 2013;65:265)
- Can detect with real time PCR (Cancer Genet 2013;206:130)
- Loss of CD16a in children is associated with recurrent viral infections
- Pathophysiology:
- Gene is similar to that for CD16b
- Binds various IgG molecules, including rheumatoid factor
- Mediates antibody dependent cytotoxicity of foreign cells, phagocytosis and other antibody dependent responses but if target cell has class I MHC, the NK cell's killer cell inhibitory receptor (KIR) inhibits cytolysis
- Mediates platelet satellitism (Am J Clin Pathol 1995;103:740)
- Affinity to ligand is regulated by glycosylation (Immunology 2003;110:335)
- Uses by pathologists:
- NK cell and macrophage marker
- Used to subtype leukemia / lymphomas
- Note: preincubation with CD16 / CD32 antibodies is commonly used to prevent nonspecific binding
- Positive staining - normal: NK cells, granulocytes, monocytes / macrophages, T cells (reactive), immature thymocytes and placental trophoblast
- Positive staining - disease:
- NK proliferative disorders, hepatosplenic alpha beta and gamma delta T cell lymphomas (variable), T cell large granular lymphocyte leukemia (variable)
- CD16 expression, normally absent from eosinophils, is upregulated with allergic conditions (J Allergy Clin Immunol 2002;109:46)
- Or when stimulated in vitro with platelet activating factor or IFNgamma (Int Arch Allergy Immunol 2004;134:165)
- Negative staining: basophils; NK / T cell lymphoma nasal type
- Reference: OMIM: 146740 [Accessed 10 May 2021]
CD16b
- Most common receptor for the Fc domain of IgG on leukocytes
- Also known as Fc gamma receptor III B, low affinity immunoglobulin gamma Fc region receptor III-B
- Has allotypes that define the human neutrophil antigen 1 (HNA 1 and NA) system involved in major post transfusional reactions (Tissue Antigens 2004;64:119)
- Polymorphisms are associated with susceptibility to idiopathic pulmonary fibrosis (Lung 2010;188:475)
- Polymorphisms may be associated with malaria (PLoS One 2012;7:e46197, Hum Genet 2012;131:289)
- Low copy number is associated with glomerulonephritis in systemic lupus erythematosus (Nature 2006;439:851)
- CD16+ eosinophils are upregulated in allergic conditions (J Allergy Clin Immunol 2002;109:463)
- Pathophysiology:
- Highly homologous to CD16a
- Only Fc receptor linked to the plasma membrane by a GPI (glycosylphosphatidylinositol) anchor
- Occurs in 2 codominantly expressed allelic variants, NA1 and NA2, which exhibit different binding affinities for IgG1 and IgG3 subclasses
- No significant clinical use by pathologists
- Positive staining - normal: neutrophils, basophils (J Immunol 2009;182:2542)
CD17 / CDw17
- Most abundant glycosphingolipid in neutrophils; not a protein
- Also known as lactosylceramide
- CD17 is also a type of mutation in beta-thalassemia, unrelated to CD markers (Fetal Diagn Ther 2010;27:25)
- Pathophysiology:
- Defines successive stages in maturation of myeloid cell (Cell Mol Biol Lett 2003;8:911)
- Rapidly and extensively down modulated on activated granulocytes (J Immunol 1989;142:2784)
- Acts as a lipid second messenger in mediating TNF alpha, platelet derived growth factor and oxidized LDL induced phenotypic changes in cells of the vascular wall
- Acts as pattern recognition receptor in innate immunity (Arch Immunol Ther Exp (Warsz) 2013;61:217)
- Clinical features: elevated levels are present in plasma of patients with familial hypercholesterolemia and in plaque intima of aorta in patients who died of cardiovascular disease (Proc Natl Acad Sci U S A 2004;101:6490)
- No significant clinical use by pathologists
- Positive staining - normal: granulocytes, macrophages / monocytes, platelets, basophils, CD19+ B cells and tonsillar dendritic cells
CD18
- Integrin which forms the beta 2 chain of CD11a, CD11b, CD11c, CD11d to create a leukocyte adhesion molecule (OMIM: 600065 [Accessed 11 May 2021])
- Gene is designated ITGB2 (integrin beta 2)
- Combines with alpha L chain (CD11a) to form the integrin LFA1
- Combines with the alpha M chain (CD11b) to form the integrin Mac1 (macrophage antigen 1, complement receptor 3)
- Combines with the alpha X chain (CD11c) to form completement receptor 4
- Also combines with the alpha D chain (CD11d)
- Pathophysiology:
- Important for adhesion and signaling in the hematopoietic system (see CD11a, b, c)
- Also for phagocytosis (J Immunol 2002;169:2003)
- Clinical features:
- Deficiency of the CD18 component (leukocyte adhesion deficiency type 1) is a rare, inherited disorder, causing severe leukocytosis and recurrent severe bacterial infections early in life of skin and mucosal surfaces, possibly fatal, due to defective white blood cell adherence, chemotaxis, phagocytosis and bacterial killing (OMIM: 116920 [Accessed 11 May 2021], J Clin Immunol 2010;30:756)
- Note: leukocyte adhesion deficiency type 2 is due to a deficiency in CD15s
- Reduced expression also seen in Vogt-Koyanagi-Harada (VKH) syndrome (PLoS One 2011;6:e14616)
- CD11b / CD18 is receptor for Bordetella pertussis adhesin filamentous hemagglutinin (FHA) and for the adenylate cyclase toxin (ACT), which blocks neutrophil function (Infect Immun 2005;73:7317, J Exp Med 2001;193:1035)
- CD11b / CD18 induces neutrophilic response leading to killing of Steptococcus pyogenes (Eur J Immunol 2005;35:1472)
- May have role in development of diabetic retinopathy (Int J Ophthalmol 2012;5:202)
- No significant clinical use by pathologists
- Positive staining - normal: neutrophils, macrophages, monocytes, NK cells and basophils
- Negative staining - normal: often negative in acute promyelocytic leukemia (Am J Clin Pathol 2012;138:744)
CD19
- See CD19
Diagrams / tables
Microscopic (histologic) images
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