Table 1.
What we know and what we do not know about O-glycosylation of IgA1 in IgAN.
| Characteristics of serum IgA1 in IgAN | ||
| High reactivity with lectin from Helix aspersa (HAA) | Moldoveanu,2007 [32], Shimozato, 2008 [33] | |
| High reactivity with monoclonal antibodies | Yasutake, 2015 [152], Hiki, 2015 [154] | |
| IgA1 carbohydrates in IgAN assessed by mass spectrometry | ||
| Decrease of galactose (Gal) | Hiki, 1998 [167], Inoue, 2012 [168], Nakazawa, 2019 [169] | |
| Decrease of N-acetylgalactosamine (GalNAc) | Hiki,1998 [167], Odani, 2000 [170], Inoue, 2012 [168], Nakazawa, 2019 [169] | |
| Decrease of sialic acid | Odani, 2000 [170] | |
| Sites of glycan attachment | ||
| Occur in specific sites | Renfrow, 2005 [50], Iwasaki, 2003 [51], Takahashi, 2010 [52], Takahashi, 2012 [53] | |
| Disease in specific sites | Needs to be investigated | |
| Expression of O-glycosyltransferases in B cells | ||
| No decrease in the ratio of C1GALT1: GALNT2 or C1GALT1: C1GALT1C1 | Buck, 2008 [171] | |
| Expression of C1GALT1 and ST6GALNAC2 altered in IgA1-producing cell lines from IgAN patients | Suzuki, 2008 [76] | |
| Decreased C1GALT1 expression in IgAN CD19+ B cells | Xing, 2020 [172] | |
| O-Glycosylation characteristics of polymeric IgA1 | ||
| Polymeric IgA1 shows higher reactivity with HAA than in monomeric IgA1 | Oortwijin, 2006 [149], Suzuki, 2008 [76], Novak, 2011 [173] | |
| Polymeric IgA1 interacted with CD71 and its interaction is enhanced by sialidase and β-galactosidase | Moura, 2004 [139] | |
| Epitopes recognized by IgG/A autoantibodies | ||
| Needs to be investigated | ||
| Clinical factors related to glycosylation of IgA1 | ||
| Genetic influences | Gd-IgA1 levels are highly inherited and affected by variants of glycosyltransferase | Tam,2009 [82], Kiryluk, 2011 [83], Gharavi, 2008 [79], Lin, 2009 [84], Hastings, 2010 [85], Gale, 2017 [95], Kiryluk, 2017 [96] |
| Susceptibility to IgAN is affected by variants of glycosyltransferase | Li 2007 [86,89], Pirulli, 2009 [87], Zhu, 2009, [88] | |
| Race differences | Gd-IgA1 levels elevated in Caucasian patients | Gale,2017 [95] |
| Gd-IgA1-increasing allele is common in Europeans | Kiryluk, 2017 [96] | |
| MicroRNA regulating C1GALT1 and GALNT2 overexpressed in Caucasian patients | Serino, 2016 [100] | |
| Age differences | Needs to be investigated | |
| Disease activity | No association of Gd-IgA1 levels measured by HAA-based ELISA with disease activity | Moldoveanu, 2007 [32], Shimozato, 2008 [33] |
| Positive association of Gd-IgA1 level measured by HAA-based ELISA with disease activity | Suzuki, 2014 [156], Sun, 2016 [155], Zhao, 2012 [157], Maixnerova, 2019 [158] | |
| Gd-IgA1 levels measured by KM55 associated with disease progression or recurrence | Wada, 2018 [160], Temurhan, 2017 [162] | |
| Longitudinal changes | Longitudinal changes of Gd-IgA1 serum levels by HAA ELISA before and after therapy need additional studies | Shimozato, 2008 [33], Suzuki, 2014 [156], Lafayette, 2017 [159] |
| O-Glycoform analyzed by MS changes between, before and after therapy | Iwatani, 2012 [174] | |