Table I. Ags bound by highly reactive Abs in maternal milk and serum and in newborn cord serum.
| IgG |
IgM |
IgA |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Associations |
Serum |
Milk |
Serum |
Milk |
Serum |
Milk | |||||||
| Ags | Description | Cancer | Autoimmune Disease | M/C | M | C | M | C | |||||
| Viral/Bacterial | Diphtheria toxoid | 100% | 78% | 88% | 72% | 71% | 78% | ||||||
| HBcAg | Hepatitis B protein | 100% | 83% | 50% | 50% | 100% | 89% | ||||||
| HBsAg ayw | Hepatitis B surface Ag | 79% | 21% | 15% | |||||||||
| Varicella zoster virus | Herpes, Chickenpox | 90% | |||||||||||
| EBV EBNA1 | EBV | 94% | 78% | 22% | |||||||||
| West Nile | 66% | 15% | 15% | ||||||||||
| HSV-1 gG | Herpes virus | 86% | 39% | ||||||||||
| Vaccines | Influenza | 98% | 15% | 21% | |||||||||
| Pneumococcal saccharide | 79% | 21% | 82% | 37% | |||||||||
| Priorix tetra | 89% | 31% | |||||||||||
| Hormones | Atosiban | Inhibits oxytocin, vasopressin | Inhibits cell growth (24) | 22% | |||||||||
| G-CSF | G-CSF | Stimulates WBCs and stem cells | Immune regulator (25) | 50% | |||||||||
| GHRH | Growth hormone–releasing hormone | Potentiates chemotherapy (26, 27) | Deficient in Hashimoto's thyroiditis (28) | 83% | 92% | ||||||||
| Glucagon | Stimulates glucose production | Inhibits pancreatic cancer cells via PI3K/Akt pathway (29) | Blocking glucagon affects mouse diabetes (30) | 84% | 22% | 78% | |||||||
| HGH | Growth hormone | Enhances cancer growth (31) | Autoantibodies in idiopathic hypopituitary disease (32) | 87% | 68% | 66% | |||||||
| Leptin tA | Regulates energy use | Regulates hepatocellular carcinoma (33) | Promotes lupus; affects T cell autoimmunity: T regulatory cells (34) and Th17 cells (35) | 97% | 91% | 28% | 50% | ||||||
| Plasma proteins | C protein | Blood coagulation factor | 50% | ||||||||||
| F3 coagulation factor III | Reduced survival in NSCLC (36) | 56% | |||||||||||
| HDL | High-density lipoprotein | Associated with survival in NSCLC (37) | Anti-inflammatory (38) | 80% | 28% | 57% | 39% | ||||||
| LDL | Low-density lipoprotein | Level is predictor of breast tumor progression (39) | Autoantibodies in myasthenia gravis (40) | 55% | 59% | 33% | 50% | 33% | |||||
| Tissue | BIRC2 | Baculoviral IAP repeat-containing protein 2 | Cervical squamous cell carcinomas (41) | Elevated in MS (42) | 33% | ||||||||
| CA125 | Mucin family | Levels related to ovarian cancer (43) | Elevated in SLE (44) | 79% | 100% | 99% | 61% | 89% | 100% | ||||
| EEF1A1 | Eukaryotic translation elongation factor 1A | Oncogenic effects (45) | 73% | 51% | |||||||||
| EIF4G1 | Eukaryotic translation initiation factor 4 γ 1 | Nasopharyngeal carcinoma (46) | Citrullinated autoantigen in RA (47) | 22% | |||||||||
| Fibronectin | Correlates with invasion and metastasis (48); (49) | Impairs remyelination in MS (50) | 100% | ||||||||||
| Gelsolin | Actin-binding protein | Affects cancer cell adhesion (51) | Expressed in RA (52) | 50% | 94% | ||||||||
| MOG | MS (53) | 22% | 63% | 55% | 69% | ||||||||
| MUC1 | Mucin 1 | Oncoprotein active in progression (54) | Affects EAE (55) | 65% | |||||||||
| Myosin | Breast cancer (56) | Carditis (57) | 52% | 44% | |||||||||
| Neurotrophin-3 | In breast cancer metastasis (58) | Protects against CNS inflammation (59) | 73% | ||||||||||
| SCF | Stem cell factor | Cancer cells (60) | 22% | ||||||||||
| S100A9 | Migration inhibitory protein 14 | In muscle invasive bladder cancer (61) | In RA synovial fluid (62) | 58% | |||||||||
| Enzymes | BCMO1 | β-carotene metabolism to vitamin A | Affects cancer cell invasion (63) | 50% | |||||||||
| Catalase | Downregulated in tumors (64) | Autoantibodies in RA and SLE (65) | 90% | ||||||||||
| Citrate synthase | Enhanced in pancreatic cancer (66) | Autoantibodies allograft nephropathy (67) | 58% | 89% | 83% | ||||||||
| GST | Prognostic in breast cancer (68) | Autoantibodies in various autoimmune diseases (69) | 55% | 72% | 44% | 50% | |||||||
| PTGDS | PG-H2 d-isomerase | In testis cancer (70) | Suppresses CNS inflammation (71) | 89% | |||||||||
| RIPK2 | Receptor-interacting serine/threonine-protein kinase 2 | Affects hepatoma cells (72), (73) | In asthma, arthritis, and MS (74) | 60% | |||||||||
| Transglutaminase 2-tgm2 | Gliomas (75), (76) | In celiac disease and diabetes (77) | 33% | 22% | |||||||||
| Immune modulator | BETA2 microglobulin | Autoantibodies are tumoricidal (78) | Increased in SLE (79) | 58% | |||||||||
| HSP60 | Heat shock protein 60 | Autoantibodies in ovarian cancer (80) | In various diseases (81) | 83% | |||||||||
| HSP60-23 | Heat shock protein 60-23 | 50% | |||||||||||
| HSP70B | Heat shock protein 70B | Expression affects colon cancer cells (82) | 91% | 39% | 28% | ||||||||
| Laminin | Tumor invasion (83) | SLE (84) | 78% | 72% | |||||||||
| MIF | Macrophage migration inhibitory factor | Squamous cell carcinomas (85) | Affects EAE (86) | 71% | 91% | 61% | 79% | 50% | |||||
| RELA | NF | Inhibits the NF-κB pathway (87) | Inhibits psoriatic skin (88) | 65% | 56% | ||||||||
| IMP-2 | IGF-II mRNA-binding protein | Muscle cell motility (89) | 90% | 33% | 74% | 62% | 72% | 69% | |||||
Shown are Ags that were highly reactive (95th percentile) to IgG, IgM, and IgA Abs in >50% of the individual mother (M) or newborn cord (C) sera or 15% for the milk. Missing values indicate that less than this percentage of the subjects were highly reactive to the Ag. In terms of raw reactivities: the 95th percentile in the maternal dataset corresponds to 10,000–55,000 ruf (see signal intensity in Materials and Methods) for IgG, 17,000–31,000 for IgM, and 3,800–18,000 for IgA. The 95th percentile in the newborns dataset corresponds to 10,000–55,000 for IgG, 20,000–40,000 for IgM, and 5,000–25,000 for IgA. The 95th percentile in the milk corresponds to 1,000–9,000 for IgG, 7,000–19,000 for IgM, and 9,000–24,000 for IgA.
EAE, experimental autoimmune encephalomyelitis; IAP, inhibitor of apoptosis protein; IGF, insulin-like growth factor; MS, multiple sclerosis; NSCLC, non–small cell lung cancer; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.