IgA: Difference between revisions

:These data must be taken into account with other hinge region characteristics <ref name="five"/>. IgA1’s hinge region contains 5 sites of O-glycosylation, while IgA2’s hinge region contains none. In addition, IgA1’s hinge region contains 10 Pro residues, while IgA2’s region contains 6.  In comparison, IgG’s hinge region contains No glycine residues reside in the hinge regions of either IgA1 or IgA2. The presence of prolines, the absence of glycine and the presence of glycosylated residues in IgA1 all amount to '''increased hinge rigidity''' in comparison to IgG1.  

'''N-glycosylation'''

:In the harsh mucosal environment, glycosylated residues protect the protein from proteases <ref name="five"/>. Both IgA1 and IgA2 display N-glycosylated residues. IgA1 has 3, at N263 on beta strand B on the Ch2 chain and on the J tail at N459. In IgA2, additional sites of N-glycosylation include Asn166 on the beta strand G of Ch1 and Asn337 of beta strand G on Ch2. Some alloforms of IgA2 are also N-glycosylated at Asn211 on Ch2. An increased need for protection against proteolytic cleavage at the hinge region accounts for the presence of O-glycosylation in IgA1’s hinge region, particularly cleavage by bacterial metalloproteases. The glycosylation residues provide increased steric hindrance, and creating difficulty in fitting the peptide in the protease’s active site. In comparison to IgG, which is only 2.9% (w/w) glycosylated, IgA1 is 9.5% (w/w) and IgA2 is 11% (w/w) glycosylated. Overall, IgA1 is more susceptible to proteases than IgA2.

==sIgA1 and sIgA2==  

:Binding of the secretory component to the convex edge of the Fc region of dimeric IgA1 maintains <scene name='Rebecca_Martin/Sandbox1/Siga1def/1'>Secretory IgA1</scene> in a near planar conformation, <ref name="nineten" />, <ref name="eight" />. The Fc regions align end to end without overlap, and the fab fragments remain in alignment with the Fc plane. In contrast, <scene name='Rebecca_Martin/Sandbox1/Siga1/1'>Secretory IgA2</scene> fab fragments remain out of alignment with the Fc plane. Because the secretory component resides at the convex region of the Fc portion, the D1 and D5 impart steric hindrance on the fab fragments, which are forced out of alignment. Consequently, IgA2 assumes a nonplanar conformation. The longer hinge region of IgA1 allows it to maintain its planar conformation.  

== Implications in Medicine and Science ==

[[Image:IgA_IFA.jpg|thumb|Immunofluorescence detecting IgA in IgA glomerulonephritis. From http://www.unckidneycenter.org/images/IgA_IFA.jpg, with permission]]

:IgA nephropathy is the most prevalent cause of chronic glomerulonephritis in the world and is caused by polymeric IgA1 deposited at the kidney glomeruli <ref name="eight"/>. Notably, 90% of serum IgA is IgA1, mostly in the monomeric form. The observation that individuals with IgA myeloma [http://en.wikipedia.org/wiki/Multiple_myeloma] lack nephropathy suggests an abnormality in IgA structure, leading to an abnormal amount of polymerization. Steric hindrance of the fab segments normally limits the amount of polymerization of IgA. Bonner, et al proposes that a disturbance in the hinge region or an absence of fab. Similarly, decreased O-glycosylation might could destabilize the hinge region, allowing IgA to self associate. Likewise, destabilizing this region might make IgA susceptible to cleavage of fab fragments by bacterial proteases, leading to self aggregation and renal pathology. For more information on IgA nephropathy: [http://http://www.unckidneycenter.org/contact.html]. <ref name="sn">Falk, R. "IgA Nephropathy." UNC Kidney Center, from http://www.unckidneycenter.org/kidneyhealthlibrary/iganephropathy.html.</ref>.