Overview of IgA
IgA is the most abundant immunoglobulin in the human body. It is found in tissues and in secretions, including pulmonary and nasal mucosal secretions, especially from the GI tract and the respiratory tract in the form of saliva, tears, breast milk, but has very low levels in serum. This reflects its role in mucosal immunity and the development of tolerance. In secretions, it is present in dimeric form, and the complex also includes a J chain and a secretory piece. All of these components are necessary in order for secretory IgA to preserve its function. IgA2 after forming a dimer has a shorter hinge than IgA1 and is therefore thought to confer more resistance to bacterial proteolytic enzymes.
Fig.1 Cartoons of the different forms of human IgA antibodies. (Wines, 2006)
IgA Related Diseases
IgA and IgA receptors occupy key roles in mucosal and systemic immunity. Defects in IgA receptors profoundly affect immunohemostasis and can result in pathologies as diverse as allergy, gut autoimmunity, vasculitis, and IgA nephropathy. IgA-associated renal diseases likely arise due to glomerular deposition of IgA-containing circulating immune complexes that escape normal clearance. This process may ensue in patients with immunoglobulin type A nephropathy (IgAN) or Henoch-Schönlein purpura nephritis (HSPN) because the large size of the complexes precludes access to the hepatic asialoglycoprotein receptor, while wider endothelial fenestrae in the glomeruli permit the complexes to enter renal mesangium. Patients with other disorders may also develop immune-complex glomerulonephritis in which IgA plays a pivotal role. Mesangial deposits of IgA arise in patients with cirrhosis because the hepatic receptor for IgA is dysfunctional. Patients infected with the hepatitis C virus (HCV) show augmented production of IgA, perhaps due to virus-induced transformation of B cells. IgA-associated nephritis frequently afflicts patients with end-stage cirrhosis due to chronic HCV infection.
Common IgA related diseases:
- IgA Nephropathy
- Selective IgA Deficiency
- IgA in Dermatitis Herpetiformis
- IgA in Celiac Disease
- IgA in Inflammatory Bowel Disease (IBD)
- Linear IgA Bullous Disease
- IgA in Liver Diseases
- IgA in Sjögren's Syndrome
Fig. 2 Proteomic approaches for identifIcation of urinary polypeptide biomarkers of a specific disease. (Julian, 2007)
Other Functions of IgA
There is more to IgA than a barrier function, as engaging cellular IgA receptors can deliver antigens to the immune system, and engaging effector leukocytes can trigger potent protective, or pathological, inflammatory reactions. In humans, serum IgA, still the second most abundant serum antibody class plays both pro- and anti-inflammatory roles and interfaces with the mucosal and systemic immunity systems. Serum IgA is predominantly IgA1, and this antibody subclass also predominates in mucosal effector sites such as the mammary gland, salivary glands, nasal mucosa, bronchial mucosa, and the upper digestive tract. The IgA2 subclass is, however, more abundant than IgA1 in the colon. These antibody subclasses are highly homologous except for the short mucin-like hinge region which is unique to primate IgA1 and is responsible for some of the unique receptor and lectin-binding properties of this molecule.
Services at Creative Biolabs
IgA-related diseases are important parts of non-IgG antibody-relevant diseases and there are many pieces of research focusing on these parts. Creative Biolabs has rich experience in non-IgG antibody researches and has established a comprehensive technology platform offering a variety of non-IgG antibody related services including but not limited to:
- Non-IgG Antibody Discovery
- Non-IgG Antibody Engineering
- Non-IgG Antibody Production and Purification
- Non-IgG Antibody Characterization
- Non-IgG Antibody PK/PD Evaluation
- Non-IgG Antibody Developability Improvement
If you are interested in IgA-related services or you are also focusing on non-IgG antibodies, please don't feel free to contact us for more information.
References
- Wines, B. D. and Hogarth, P. M. IgA receptors in health and disease. Tissue Antigens. 2006, 68(2): 103-14.
- Julian, B. A.; et al. Urinary biomarkers of IgA nephropathy and other IgA-associated renal diseases. World J Urol. 2007, 25(5): 467-76.
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